METHODS FOR ENHANCING THE QUALITY OF LIFE OF A SENIOR ANIMAL

FIELD OF THE INVENTION

[0001] The present invention relates generally to methods for modulating biological functions associated with the aging process of an animal and particularly to using food compositions containing omega-3 polyunsaturated fatty acids for modulating biological functions associated with the aging process of a senior or super senior animal.

BACKGROUND OF THE INVENTION

[0002] Companion animals such as dogs and cats frequently require differing diets depending on their life stage (age), size, body composition, and breed. Both dog and cat nutrient requirements can be separated into three different life-stages, based on age: growing dogs (or cats), adult dogs (or cats), and senior dogs (or cats). The latter category, senior dogs (or cats), can be further separated into two stages, which include senior (or mature adult) and super senior (or geriatric). Dogs are further separated into different categories for regular breed dogs versus large-breed dogs.

[0003] Essential fatty acids, consisting of omega-3 and omega-6 polyunsaturated fatty acids, are critical nutrients for the health of an animal. These nutrients, however, either cannot be made by animals or cannot be made in sufficient amounts to elicit benefits and therefore must be consumed in an animal's diet. See, e.g., Hornstra, G., et al., "Essential fatty acids in pregnancy and early human development", Eur. J. Obs. & Gyn. and Reprod. Biology, 61 :57-62 (1995). It has previously been postulated that Docosahexaenoic Acid ("DHA"), an omega-3 polyunsaturated fatty acid, is effective in increasing the maze-learning ability and brain functions in aged mice. See, Lim, S. -Y., "Intakes of dietary docosahexaenoic acid ethyl ester and egg phosphatidylcholine improve maze-learning ability in young and old mice", J. Nutr., 130:1629-1632 (2000).

[0004] Rogers discusses the theory of the potential use of antioxidants to slow the deterioration of cognitive function, particularly in the elderly. See Rogers, P., "A healthy body, a healthy mind: long-term impact of diet on mood and cognitive function", Proceedings of the Nutrition Society, 60:135-143 (2001).

[0005] Despite the studies and developments relating to improving cognitive abilities, there continues to be a need for methods for enhancing the quality of life of senior animals, as measured by, e.g., enhanced alertness, improved vitality, cartilage protection, maintenance of muscle mass, enhanced digestibility, and improved skin and pelage quality in senior and super senior animals.

[0006] As previously reported, the super senior pet food composition described herein may be administered to achieve this result. Additionally, we now report herein our surprising discovery that the enhanced quality of life of senior and super senior animals achieved by the administration of the pet food compositions disclosed herein is reflected at the genomic level. Specifically, as described in detail in the Examples below, gene chip data indicate that the expression of genes that encode proteins associated with several biological pathways such as blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway ,the aging process, and electron transport are modified, i.e., in general, the majority are beneficially altered through administration to the animal of the super senior pet food compositions described herein.

SUMMARY OF THE INVENTION

[0007] The invention encompasses methods for improving or enhancing the quality of life of senior and super senior animals by feeding the animal a composition comprising at least about 9% by weight protein, at least about 5% by weight fat, and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid.

[0008] In one embodiment, the invention encompasses compositions effective to enhance an animal's quality of life, wherein enhanced quality of life is evidenced by improvement in one or more characteristics chosen from alertness, vitality, cartilage protection, muscle mass maintenance, digestibility, and skin and pelage quality.

[0009] In another embodiment, the invention encompasses compositions comprising at least one omega-3 polyunsaturated fatty acid chosen from docosahexaenoic acid ("DHA") and eicosapentaenoic acid ("EPA"). In an additional embodiment, the method comprises feeding the animal a composition further comprising at least one antioxidant and at least one nutrient chosen from choline, manganese, methionine, cysteine, L-carnitine, lysine, and mixtures thereof.

[0010] In one embodiment, the invention encompasses compositions effective to improve or enhance the animal's quality of life, wherein enhanced quality of life is evidenced by improvement in one or more biological pathways chosen from blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport.

[0011] In another embodiment, the invention encompasses compositions effective to enhance the animal's quality of life, wherein enhanced quality of life is evidenced by a beneficial change in expression of one or more genes which encode proteins associated with or related to biological pathways chosen from blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport.

[0012] In yet another embodiment, the invention encompasses methods to treat an animal suffering from a disorder or disease associated with or related to a biological pathway chosen from blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport comprising administering to said animal an effective amount of a composition of the present invention. In one embodiment, the composition includes at least about 9% by weight protein, at least about 5% by weight fat, and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid. In a further embodiment said composition comprises at least one omega-3 polyunsaturated fatty acid chosen from docosahexaenoic acid ("DHA") and eicosapentaenoic acid ("EPA"). In yet an additional embodiment, the composition further comprises at least one antioxidant and at least one nutrient chosen from choline, manganese, methionine, cysteine, L- carnitine, lysine, and mixtures thereof. In additional embodiments, the composition may comprise the components disclosed in Table 1 or Table IA.

[0013] In another embodiment, the invention encompasses methods of measuring or characterizing the enhancement in the quality of life of an animal, particularly a senior or super senior animal, fed a composition described herein by quantitating the gene expression levels of one or more genes chosen from those disclosed in Tables 5-14 in said animal prior to and after feeding a composition disclosed herein and comparing said levels in the animal wherein an enhancement in the quality of life of said animal is reflected by a beneficial change in gene expression levels in said animal.

[0014] Another embodiment encompasses methods of altering the expression of at least one peptide in a mammal, the method comprising administering to the mammal a composition comprising at least about 9% by weight protein; at least about 5% by weight fat; and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid, wherein the at least one peptide is selected from the group consisting of X, Y and Z. With regard to the various embodiments presented herein, it is contemplated herein that the senior or super senior animal may be a senior or super senior large breed canine, regular breed canine, small breed canine or feline.

[0015] In another embodiment, the invention encompasses methods for screening one or more test compounds for its ability to alter the expression of at least one gene of interest in a mammal, the method comprising administering a control composition to a control group of mammals and determining the levels of expression of the at least one gene of interest, administering the one or more test compositions to an experimental group of mammals and determining the levels of expression of the least one gene of interest, wherein the test composition comprises at least about 9% by weight protein; at least about 5% by weight fat; and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid, and determining the differences in expression levels in the at least one gene of interest between the control and experimental groups of mammals after each group has been administered their respective compositions, wherein a difference in the expression levels of the at least one gene of interest indicates that the test composition is capable of altering the expression of the at least one gene of interest. [0016] Another embodiment encompasses methods for screening one or more test compounds for its ability to alter the expression of at least one gene of interest in a mammal, the method comprising administering a control composition to a control group of mammals and determining the levels of expression of the at least one gene of interest, wherein the control composition comprises at least about 9% by weight protein; at least about 5% by weight fat; and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid, administering the one or more test compositions to an experimental group of mammals and determining the levels of expression of the least one gene of interest, and determining the differences in expression levels in the at least one gene of interest between the control and experimental groups of mammals after each group has been administered their respective compositions, wherein a difference in the expression levels of the at least one gene of interest indicates that the test composition is capable of altering the expression of the at least one gene of interest.

[0017] Other and further objects, features, and advantages of the present invention will be readily apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

[0018] It is contemplated that the invention described herein is not limited to the particular methodology, protocols, and reagents described as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention in any way. [0019] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the advantageous methods, devices and materials are now described. All publications mentioned herein are incorporated by reference for the purpose of describing and disclosing the materials and methodologies that are reported in the publication which might be used in connection with the invention. [0020] In practicing the present invention, many conventional techniques in molecular biology may be used. These techniques are well known and are explained in, for example, F. M. Ausubel, Ed. Current Protocols in Molecular Biology, Volumes I, II, and III, (Wiley, New York), 1997 ; J. Sambrook, E. F. Frhseh, 1 ^"' . Maniatis, EcLs., Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, Cold Spring Harbor. New York, 1989), [0021] As used herein and in the appended claims, the singular forms "a", "an", and "the" include plural reference unless the context clearly dictates otherwise.

[0022] The terms "senior" or "mature adult" refers to the life-stage of an animal. For small or regular breed canines, the "senior" life stage is about 7 to about 10 years of age. For felines, the "senior" life stage is about 7 to about 12 years of age. For large breed canines, over 5 years of age represents "super senior" as described below.

[0023] The terms "super senior" or "geriatric" refers to a specific life-stage of an animal. For small or regular breed canines, the super senior stage is any age greater than 10 years of age. For large breed canines, the super senior stage is any age greater than 5 years of age. For felines, the super senior stage is any age greater than 12 years of age.

[0024] The term "large breed" canine means a canine that normally weighs about 55 pounds or more when an adult.

[0025] The term "regular breed" canine means a canine that normally weighs less than about 55 pounds when an adult.

[0026] The term "small breed" canine means a canine that weighs less than about 20 pounds when an adult.

[0027] The term "super senior pet food composition" refers to any and all of the pet food compositions disclosed herein.

[0028] The term "carbohydrate" as used herein includes polysaccharides (e.g., starches and dextrins) and sugars (e.g. sucrose, lactose, maltose, glucose, and fructose) that are metabolized for energy when hydrolyzed. Examples of carbohydrates suitable for inclusion in the compositions disclosed herein include, but are not limited to, corn, grain sorghum, wheat, barley, and rice.

[0029] The term "antioxidant" means a substance that is capable of reacting with free radicals and neutralizing them. Illustrative examples of such substances include beta-carotene, selenium, coenzyme QlO (ubiquinone), luetin, tocotrienols, soy isoflavones, S- adenosylmethionine, glutathione, taurine, N-acetylcysteine, vitamin E, vitamin C, lipoic acid and L-carnitine. Examples of foods containing useful levels of one or more antioxidants include but are not limited to ginkgo biloba, green tea, broccoli, citrus pulp, grape pomace, tomato pomace, carrot spinach, and a wide variety of fruit meals and vegetable meals. It will be understood by one of skill in the art that while units of antioxidants may be provided herein as "ppm", appropriate amounts of antioxidants may also be provided as "IU/kg" where appropriate and customary for a given antioxidant such as, e.g., Vitamin E. [0030] The terms "beneficial change" in gene expression, or gene expression may be "beneficially altered" and like terms refer to a modification in gene expression (e.g., up or down regulation of mRNA levels) such that levels of proteins or peptide chains encoded by the genes may be correspondingly modified such that an associated biological pathway may be more likely to function normally, such as in a healthy adult animal and with less tendency to reflect pathological changes in the pathway that, e.g., may be typical of a super senior or geriatric animal. Generally, beneficial changes in gene expression relate to improved health and/or reduced propensity for disease in an animal. As used herein, measuring differences in "gene expression" and like terms refer to, e.g., characterizing whether expression of a gene is up or down regulated in an animal compared to a control level. Gene expression levels can assessed by determining mRNA levels for a corresponding gene, or they may be inferred by determining protein or peptide chain levels. To be clear, determining "gene expression" or "gene expression levels" as used herein includes, but is not limited to, determining either corresponding RNA levels or peptide/protein levels or both. The invention is not limited to a particular method for determining protein or peptide or RNA levels, all of which are well known in the art. Moreover, gene expression and gene expression levels can be assessed in any cell or tissue that is appropriate for expression of the gene of interest. In one embodiment, gene expression is assessed in blood cells. In a more specific embodiment, the blood cells are lymphocytes. In an even more specific embodiment, the cells are T-lymphocytes. Other cell types include, but are not limited to, muscle cells, nerve cells, glial cells, endothelial cells, skin cells, liver cells, kidney cells, bone cells, other types of blood cells, such as but not limited to, macrophages. The cells may be primary cells, i.e., taken directly from an animal, such as cells isolated from recently drawn blood. The cells may also be non-primary, i.e. an established cell line through passage or even an immortalized cell line, such that the methods determining gene expression levels can be performed on established animal cell lines, e.g., CHO cells, prior to administration of a composition to an animal.

[0031] As used herein, a "gene" is a DNA molecule where at least a portion of which is transcribed into an RNA molecule. The DNA molecule may or may not include non- transcribed regions and/or non-translated regions, such as but not limited to introns, promoters, enhancer regions, 5' untranslated regions.

[0032] The methods include the genes listed herein, as well as homo logs. Thus, the methods of the present invention are not limited to the genes whose database accession numbers are disclosed herein and include homo logs thereof. As used herein, a homo log of a gene listed herein means a gene whose coding or non-coding sequence may vary slightly from the reference sequence but also codes for the same or "equivalent" protein or peptide in a different organism. For example, the methods of the present invention relate to expression of phosp ho lipase A2 in at least a canine. A homo log of the canine phospho lipase A2 gene would include, but would not be limited to, the feline phospholipase A2 gene, the bovine phospholipase A2 gene, the porcine phospholipase A2 gene, the equine phospholipase A2 gene and the primate phospholipase A2 gene. Homologs also include variations in the coding or non-coding sequences that account for slight variations across species. For example, the present invention relates to the human phospholipase A2 gene, and a homo log thereof would include, but would not be limited to a monkey or chimpanzee phospholipase A2 gene. [0033] As used herein, "improving" or "enhancing" the quality of life of an animal refers to as an improvement or enhancement in one or more characteristics chosen from alertness, vitality, protection of cartilage, maintenance of muscle mass, digestibility, and skin and pelage quality. Additionally, improvement/enhancement in blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport are also contemplated.

[0034] An "improvement" or an "enhancement" in a characteristic or biological pathway refers to a modification in said characteristic or biological pathway such that there is a tendency for the characteristic or pathway to appear and/or function normally and with less tendency to reflect pathological changes in the characteristic or pathway that, e.g., may be typical of a super senior animal.

[0035] As used herein, methods to "treat" an animal suffering from a disease or disorder is also meant to encompass methods to prevent and/or to ameliorate the disease or disorder as well.

[0036] As used herein, "genes associated with the aging process" or "aging genes" or like terms refers to those genes which may be involved in the process of senescence in an animal.

These genes may include, e.g., genes that encode for proteins that have a role in a number of biological functions such as inflammation, DNA repair or cell survival, fat or cholesterol metabolism, protein synthesis, immune regulation, cell growth and cell death.

[0037] Similarly, the "aging process", as the term is used herein, refers to the process of senescence in an animal and may include changes in biological functions such as, e.g., inflammation, DNA repair or cell survival, fat or cholesterol metabolism, protein synthesis, cell growth and cell death.

[0038] As used herein, the phrase "modulating biological functions associated with the aging process" refers to op-regulating or down-regulating genes, which may be involved in the process of senescence in an animal. These genes may include, e.g., genes that encode for proteins that have a role in a number of biological functions such as inflammation, DNA repair or cell survival, fat or cholesterol metabolism, protein synthesis, immune regulation, cell growth and cell death.

The Invention

[0039] The present invention encompasses compositions and methods for improving or enhancing the quality of life of a senior or super senior animal. The methods comprise feeding the animal a composition comprising at least about 9% by weight protein, at least about 5% by weight fat, and at least about 0.05% by weight omega-3 polyunsaturated fatty acid. The methods are useful for enhancing alertness, improving vitality, protecting cartilage, maintaining muscle mass, enhancing digestibility, and improving skin and pelage quality in a senior or super senior animal. The methods are also useful for improving in an animal one or more biological pathways chosen from blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and the electron transport pathway, such improvements also being reflected in overall beneficial changes at the genomic level. Methods for treating animals suffering from disorders or diseases associated with or related to these biological pathways comprising administering the compositions of the present invention are also contemplated herein.

[0040] Without being bound by theory, the benefits of the invention may be the result of physiological effects from the addition of omega- 3 polyunsaturated fatty acids to a senior or super senior animal's diet. Similarly, the antioxidants, choline, and other nutrients may play a role in enhancing a senior or super senior animal's quality of life.

[0041] Although the methods of the present invention may improve an animal's quality of life by enhancing all of the above described characteristics or improving all of the described biological pathways, it is not necessary to demonstrate substantial improvements in each of the characteristics or pathways to achieve the "enhanced quality of life" as defined herein. [0042] When the compositions are administered to a senior or super senior animal, the animal experiences an enhanced quality of life, e.g., exhibits or experiences one or more of enhanced alertness, improved vitality, protected cartilage, maintained muscle mass, enhanced digestibility, improved skin and pelage quality, as well as improvements in e.g., blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process and the electron transport pathway as indicated by overall beneficial changes at the genomic level. Methods for determining these measurements of quality of life are known to skilled artisans. For example, alertness can be measured by various means, including an analysis of metabolism and antioxidant markers, as well as through clinical studies with follow-up questions to participating pet owners. Potential metabolism markers may include ghrelin, GLP-I, thyroid hormone, and/or growth hormone. Potential markers of antioxidant status may include serum vitamin E, ORAC, glutathione peroxidase, alkanels, and/or cell damage indicators. Further, vitality can be measured by various means, including an analysis of metabolism and antioxidant markers, as well as through clinical studies with follow- up questions to participating pet owners. Similarly, cartilage protection can be measured by various means, including an analysis of arthritis biomarkers. Potential arthritis biomarkers may include type II collagen synthesis, matrix metaloproteinase, osteocalcin, alkaline phosphatase activity, COMP, and fragments of cartilage damage. Muscle mass maintenance can be measured by various means, including an analysis of body composition and digestibility can be measured by various means, including clinical studies with follow-up questions to participating pet owners and animal feeding to determine the percentage of nutrients digested. Skin and pelage quality can be measured by various means, including clinical studies with follow-up questions to participating pet owners. Additionally, as discussed above, improvements in quality of life is also reflected at the genomic level, as evidenced by gene chip data which indicate beneficial changes on the expression of genes associated with various important biological pathways including blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and protection and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and the electron transport pathway. The identities of these genes are provided in the Examples below.

[0043] The methods of the invention are useful for enhancing the quality of life of humans and animals, including primates (e.g., monkeys, chimpanzees, etc.), companion animals (e.g., dogs, cats, horses, etc.), farm animals (e.g., goats, sheep, swine, cattle, etc.), laboratory animals (e.g., mice, rats, etc.), birds (e.g., domestic birds such as canaries, parrots, etc. and commercial birds such as chickens, ducks, turkeys, etc.), rodents (e.g., hamsters, guinea pigs, gerbils, rabbits, hedgehogs, ferrets, chinchillas, etc.), and wild, exotic, and zoo animals (e.g., wolves, bears, deer, etc.). In various embodiments, the animal is a cat, a dog, or a horse. [0044] The compositions of the present invention are designed to enhance digestibility and improve chewability. Canine and feline foods are typically formulated based on life stage (age), size, body composition, and breed. Thus, some embodiments of the present invention include compositions that are formulated to address specific nutritional differences between regular or small breed dogs, large breed dogs, and cats.

[0045] The invention provides methods utilizing a variety of compositions containing at least one omega-3 polyunsaturated fatty acid. The compositions include foods, supplements, treats, and toys (typically chewable and consumable toys). The methods also provide the compositions to the designated animals over a period of time that is long enough to effectuate the improved quality of life. In one embodiment, the method provides the animal with a composition for at least thirty days.

[0046] The compositions for use in the methods of the present invention generally have an omega-3 polyunsaturated fatty acid content of at least about 0.02% (or about 0.05 % to about 10%, or about 0.1% to about 6%) by weight on a dry matter basis. In some embodiments, the omega-3 polyunsaturated fatty acid is DHA. In other embodiments, the omega-3 polyunsaturated fatty acid is EPA. In still other embodiments, the omega-3 polyunsaturated fatty acid comprises a mixture of DHA and EPA.

[0047] In some embodiments, the composition containing omega-3 polyunsaturated fatty acid is a food. Although both liquid and solid foods are provided, solid foods are typically advantageous. Foods include both dry foods and wet foods. Some of the non-polyunsaturated fatty acid components of the food, and useful proportions, include those listed in Table 1.

Table 1

[0048] In one embodiment, the methods of this invention comprise feeding a super senior animal a composition in an amount effective to enhance the animal's quality of life. Such compositions generally comprise:

(a) 0.02% (or about 0.05 % to about 10%, or about 0.1% to about 6%) of at least one omega-3 polyunsaturated fatty acid, and

(b) at least one of the following: (i) about 10% to about 55% (or about 18% to about 30%, or about 33% to about 55% or about 18% to about 20% or about 33% to about 36%) protein,

(ii) about 7% to about 35% (or about 18% to about 35%, or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16% or about 18% to about 24%) fat, and

(iii) at least about .05 (or about 0.05 ppm or IU/kg to about 7500 ppm or IU/kg, or about 250 ppm or IU/kg to about 3600 ppm or IU/kg, or about 250 ppm or IU/kg to about 1650 ppm or IU/kg, or about 5 ppm or IU/kg to about 225 ppm or IU/kg, or about 0.05 ppm or IU/kg to about 2.4 ppm or IU/kg) antioxidant.

[0049] In another embodiment, the methods of this invention comprise feeding a super senior regular or small breed canine a composition in an amount effective to enhance the canine's quality of life. The composition generally comprises:

(a) at least one of the following:

(i) at least about 0.02% (or about 0.02% to about 0.3%, or about 0.05% to about 0.3%, or about 0.05% to about 0.2%) DHA, and

(ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA,

(b) at least about 9% (or about 9% to about 30%, or about 18% to about 30%, or about 18% to about 20%) protein,

(c) at least about 7% (or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16%) fat, and

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1000 IU/kg) vitamin E, (iv) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

100 ppm to about 500 ppm, or about 100 ppm to about 301 ppm) vitamin C, (v) at least about 600 ppm (or about 600 ppm to about 2400 ppm, or about 1260 ppm to about 2400 ppm, or about 1260 ppm to about

1545 ppm) taurine, (vi) at least about 50 ppm (or about 50 ppm to about 200 ppm, or about

100 to about 160, or about 100 to about 155) lipoic acid, and (vii) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

200 ppm to about 500 ppm, or about 200 ppm to about 350 ppm) carnitine.

[0050] In another embodiment, the methods of this invention comprise feeding a super senior large breed canine a composition in an amount effective to enhance the canine's quality of life. The compositions generally comprise:

(a) at least one of the following:

(i) at least about 0.02% (or about 0.02% to about 0.3%, or about 0.05% to about 0.3%, or about 0.05% to about 0.2%) DHA, and

(ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA,

(b) at least about 9% (or about 9% to about 30%, or about 18% to about 30%, or about 18% to about 20%) protein,

(c) at least about 7% (or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16%) fat, and

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1000 IU/kg) vitamin E , (viii) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

100 ppm to about 500 ppm, or about 100 ppm to about 301 ppm) vitamin C, (ix) at least about 600 ppm (or about 600 ppm to about 2400 ppm, or about 1260 ppm to about 2400 ppm, or about 1260 ppm to about

1575 ppm) taurine, and (x) at least about 50 ppm (or about 50 ppm to about 200 ppm, or about 100 to about 160, or about 100 to about 155) lipoic acid, and

(xi) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about 200 ppm to about 500 ppm, or about 200 ppm to about 350 ppm) carnitine.

[0051] In another embodiment, the methods of this invention comprise feeding a super senior feline a composition in an amount effective to enhance the feline's quality of life. The compositions generally comprise:

(a) at least one of the following:

(i) at least about 0.05% (or about 0.05% to about 0.30%, or about 0.1% to about 0.30%, or about 0.1% to about 0.2%) DHA, and

(ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA,

(b) at least about 15% (or about 15% to about 55%, or about 30% to about 55%, or about 33% to about 36%) protein,

(c) at least about 9% (or about 9% to about 35%, or about 18% to about 35%, or about 18% to about 24%) fat, and

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1100 IU/kg) vitamin E , (xii) at least about 50 ppm (or about 50 ppm to about 300 ppm, or about

100 ppm to about 300 ppm, or about 100 ppm to about 200 ppm) vitamin C, (xiii) at least about 1100 ppm (or about 1100 ppm to about 3500 ppm, or about 2300 ppm to about 3500 ppm, or about 2300 ppm to about

2350 ppm) taurine, and (xiv) at least about 200 ppm (or about 200 to about 750 ppm, or about 400 ppm to about 750 ppm, or about 400 to about 525 ppm) carnitine, and (xv) at least about 0.05% (or about 0.05% to about 0.6%, or about 0.1% to about 0.6%, or about 0.1% to about 0.4%) cystine.

[0052] In another embodiment, the methods of this invention comprise feeding a super senior animal a composition in an amount effective to enhance the animal's alertness and vitality. The composition generally comprises:

(a) 0.02% (or about 0.05 % to about 10%, or about 0.1% to about 6%) at least one omega-3 polyunsaturated fatty acid, and

(b) at least one of the following:

(xvi) about 10% to about 55% (or about 18% to about 30%, or about 33% to about 55% or about 18% to about 20% or about 33% to about 36%) protein,

(xvii) about 7% to about 35% (or about 18% to about 35%, or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16% or about 18% to about 24%) fat,

(xviii) at least about .05 (or about 0.05 ppm to about 7500 ppm, or about 250 to about 3600, or about 250 ppm to about 1650 ppm, or about 5 ppm to about 225 ppm, or about 0.05 ppm to about 2.4 ppm) antioxidant, and

(xix) at least about 1000 ppm (or about 1000 ppm to about 5000 ppm, about 3300 ppm to about 5000 ppm, or about 2000 ppm to about 3000 ppm, or about 3000 ppm to about 4000 ppm) choline.

[0053] In another embodiment, the methods of this invention comprise feeding a super senior regular or small breed canine a composition in an amount effective to enhance the canine's alertness and vitality. The composition generally comprises: (a) at least one of the following:

(i) at least about 0.02% (or about 0.02% to about 0.3%, or about 0.05% to about 0.3%, or about 0.05% to about 0.2%) DHA, and (ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA, (b) at least about 9% (or about 9% to about 30%, or about 18% to about 30%, or about 18% to about 20%) protein,

(c) at least about 7% (or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16%) fat,

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1000 IU/kg) vitamin E , (xx) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

100 ppm to about 500 ppm, or about 100 ppm to about 301 ppm) vitamin C, (xxi) at least about 600 ppm (or about 600 ppm to about 2400 ppm, or about 1260 ppm to about 2400 ppm, or about 1260 ppm to about

1545 ppm) taurine, and (xxii) at least about 50 ppm (or about 50 ppm to about 200 ppm, or about

100 to about 160, or about 100 to about 155) lipoic acid, and (xxiii) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

200 ppm to about 500 ppm, or about 200 ppm to about 350 ppm) carnitine,

(e) at least about 1000 ppm (or about 1000 ppm to about 3200 ppm, or about 2000 ppm to about 3200 ppm, or about 2000 ppm to about 2500 ppm) choline,

(f) at least about 50 ppm (or about 50 ppm to about 150 ppm, or about 100 ppm to about 150 ppm, or about 100 ppm to about 110 ppm) manganese, and

(g) at least about 0.4% (or about 0.4% to about 2%, or about 0.9% to about 2%, or about 0.9% to about 1.2%) lysine, and

(h) at least about 0.4% to about 1.5% methionine.

[0054] In another embodiment, the methods of this invention comprise feeding a super senior large breed canine a composition in an amount effective to enhance the canine's alertness and vitality. The composition generally comprises: (a) at least one of the following: (i) at least about 0.02% (or about 0.02% to about 0.3%, or about 0.05% to about 0.3%, or about 0.05% to about 0.2%) DHA, and

(ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA,

(b) at least about 9% (or about 9% to about 30%, or about 18% to about 30%, or about 18% to about 20%) protein,

(c) at least about 7% (or about 7% to about 24%, or about 14% to about 24%, or about 14% to about 16%) fat,

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1000 IU/kg) vitamin E , (xxiv) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

100 ppm to about 500 ppm, or about 100 ppm to about 301 ppm) vitamin C, (xxv) at least about 600 ppm (or about 600 ppm to about 2400 ppm, or about 1260 ppm to about 2400 ppm, or about 1260 ppm to about

1575 ppm) taurine, and (xxvi) at least about 50 ppm (or about 50 ppm to about 200 ppm, or about

100 to about 160, or about 100 to about 155) lipoic acid, and (xxvii) at least about 50 ppm (or about 50 ppm to about 500 ppm, or about

200 ppm to about 500 ppm, or about 200 ppm to about 350 ppm) carnitine,

(e) at least about 1000 ppm (or about 1000 ppm to about 3200 ppm, or about 2000 ppm to about 3200 ppm, or about 2000 ppm to about 2500 ppm) choline,

(f) at least about 50 ppm (or about 50 ppm to about 150 ppm, or about 100 ppm to about 150 ppm, or about 100 ppm to about 110 ppm) manganese, and

(g) at least about 0.4% (or about 0.4% to about 2%, or about 0.9% to about 2%, or about 0.9% to about 1.2%) lysine, and

(h) at least about 0.4% to about 1.5% methionine. [0055] In another embodiment, the methods of this invention comprise feeding a super senior feline a composition in an amount effective to enhance the feline's alertness and vitality. The composition generally comprises:

(a) at least one of the following:

(i) at least about 0.05% (or about 0.05% to about 0.30%, or about 0.1% to about 0.30%, or about 0.1% to about 0.2%) DHA, and

(ii) at least about 0.1% (or about 0.1% to about 0.5%, or about 0.2% to about 0.5%, or about 0.2% to about 0.3%) EPA,

(b) at least about 15% (or about 15% to about 55%, or about 30% to about 55%, or about 33% to about 36%) protein,

(c) at least about 9% (or about 9% to about 35%, or about 18% to about 35%, or about 18% to about 24%) fat,

(d) at least one of the following:

(i) at least about 250 IU/kg (or about 250 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about 1500 IU/kg, or about 500 IU/kg to about

1100 IU/kg) vitamin E , (xxviii)at least about 50 ppm (or about 50 ppm to about 300 ppm, or about

100 ppm to about 300 ppm, or about 100 ppm to about 200 ppm) vitamin C, (xxix) at least about 1100 ppm (or about 1100 ppm to about 3500 ppm, or about 2300 ppm to about 3500 ppm, or about 2300 ppm to about

2350 ppm) taurine, and (xxx) at least about 200 ppm (or about 200 to about 750 ppm, or about 400 ppm to about 750 ppm, or about 400 to about 525 ppm) carnitine, and (xxxi) at least about 0.05% (or about 0.05% to about 0.6%, or about 0.1% to about 0.6%, or about 0.1% to about 0.4%) cystine,

(e) at least about 1600 ppm (or about 1600 ppm to about 5000 ppm, or about 3300 ppm to about 5000 ppm, or about 3300 ppm to about 3400 ppm) choline,

(f) at least about 50 ppm (or about 50 ppm to about 150 ppm, or about 100 ppm to about 150 ppm, or about 100 ppm to about 110 ppm) manganese, and (g) at least about 0.7% (or about 0.7% to about 3%, or about 1.4% to about 3%, or about 1.4% to about 1.7%) lysine, and

(h) at least about 0.4% to about 1.5% methionine.

[0056] In another embodiment, this invention provides a method for improving the quality of life of a senior or super senior small or regular breed canine. The method comprises feeding the canine a composition comprising: about 60% to about 70% by weight carbohydrate; about 15% to about 25% by weight protein chosen from animal protein and vegetable protein; about 5% to about 7% by weight fat chosen from animal fat and vegetable fat; about 2.5% to about 4% by weight of at least one omega-3 polyunsaturated fatty acids; about 1% to about 4% by weight fiber; about 1% to about 2% by weight minerals; and about 0.5 to about 1.5% by weight vitamins.

[0057] In another embodiment, this invention provides a method for improving the quality of life of a senior or super senior large breed canine. The method comprises feeding the canine a composition comprising: about 60% to about 70% by weight carbohydrate; about 15% to about 25% by weight protein chosen from animal protein and vegetable protein; about 5% to 10% by weight fat chosen from animal fat and vegetable fat; about 3% to about 5% by weight of at least one omega-3 polyunsaturated fatty acids; about 1% to about 4% by weight fiber; about 0.5% to about 1% by weight minerals; and about 0.75 to about 1.25% by weight vitamins.

[0058] In another embodiment, this invention provides a method for improving the quality of life of a senior or super senior feline. The method comprises feeding the feline a composition comprising: about 30% to about 35% by weight carbohydrate; about 35 % to about 50% by weight protein chosen from animal protein and vegetable protein; about 12% to about 15% by weight fat chosen from animal fat and vegetable fat; about 1% to about 2% by weight of at least one omega-3 polyunsaturated fatty acids; about 1% to about 5% by weight fiber; about 1% to about 2% by weight minerals; and about 1% to about 2% by weight vitamins.

[0059] In a further embodiment, this invention provides a method for improving the quality of life of a senior or super senior animal comprising feeding the animal (e.g., small, regular or large breed canine or feline, as the case may be) a composition comprising the components as indicated in Table IA below:

Table IA: Chemical composition of Super Senior Foods

Small/Regular

Breed Large Breed Nutrient Component Canine Canine Feline

Crude Protein, % 20.1 19.34 35.73

Fat, % 16.45 16.92 22.47

Calcium, % 0.71 0.73 0.94

Phosphorus, % 0.61 0.68 0.77

EPA, % 0.32 0.32 0.23

DHA, % 0.22 0.22 0.32

Linoleic Acid, % 3.96 4.04 5.05

Total N-3 fatty acids, % 1.3 2.24 1.14

Total N-6 fatty acids, % 3.96 3.99 5.09

Taurine, ppm 1400 15.25 2100

Carnitine, ppm 314 337 367

Methioinine, % 1 1.19 1.32

Cystine, % 0.25 0.24 0.47

Manganese, ppm 87 100 104

Vitamin E, IU/kg 1492 1525 1292

Vitamin C, ppm 127 261 141

Lipoic Acid, ppm* 101 135

* Lipoic acid based on formulated, not analyzed values.

[0060] The compositions for use in the methods of this invention further comprise at least one nutrient chosen from manganese, methionine, cysteine, mixtures of methionine and cysteine, L-carnitine, lysine, and arginine. Specific advantageous amounts for each component in a composition will depend on a variety of factors including, for example, the species of animal consuming the composition; the particular components included in the composition; the age, weight, general health, sex, and diet of the animal; the animal's consumption rate, and the like. Thus, the component amounts may vary widely, and may even deviate from the proportions given herein.

[0061] The omega-3 fatty acids may be obtained from a variety of sources. One convenient source is fish oils from, for example, menhaden, mackerel, herring, anchovy, and salmon. DHA and EPA are typical fatty acids present in such fish oils, and, together often make up a significant portion of the oil, such as about 25% to about 38% of the oil. [0062] When the composition is an animal food, vitamins and minerals preferably are included in amounts required to avoid deficiency and maintain health. These amounts are readily available in the art. The National Research Council (NRC), for example, provides recommended amounts of such ingredients for farm animals. See, e.g., Nutrient Requirements of Swine (10th Rev. Ed., Nat'l Academy Press, Wash. D. C, 197298), Nutrient Requirements of Poultry (9th Rev. Ed., Nat'l Academy Press, Wash. D. C, 1994), Nutrient Requirements of Horses (Fifth Rev. Ed., Nat'l Academy Press, Wash. D. C, 1989), Nutrient Requirements of Dogs and Cats (Nat'l Academy Press, Wash. D. C, 2006). The American Feed Control Officials (AAFCO), for example, provides recommended amounts of such ingredients for dogs and cats. See American Feed Control Officials, Inc., Official publication, pp. 126-140 (2003). Examples of vitamins useful as food additives include vitamin A, Bl, B2, B6, B 12, C, D, E, K, H (biotin), K, folic acid, inositol, niacin, and pantothenic acid. Examples of minerals and trace elements useful as food additives include calcium, phosphorus, sodium, potassium, magnesium, copper, zinc, chloride, and iron salts.

[0063] The methods of the present invention include compositions that may further contain other additives known in the art. Preferably, such additives are present in amounts that do not impair the purpose and effect provided by the invention. Examples of additives include, for example, substances with a stabilizing effect, processing aids, substances that enhance palatability, coloring substances, and substances that provide nutritional benefits. [0064] Stabilizing substances include, for example, substances that tend to increase the shelf life of the composition. Potentially suitable examples of such substances include, for example, preservatives, antioxidants, synergists and sequestrants, packaging gases, stabilizers, emulsifϊers, thickeners, gelling agents, and humectants. Examples of emulsifϊers and/or thickening agents include, for example, gelatin, cellulose ethers, starch, starch esters, starch ethers, and modified starches.

[0065] Additives for coloring, palatability ("pal enhancers"), and nutritional purposes include, for example, colorants (e.g., iron oxide, such as the red, yellow, or brown forms); sodium chloride, potassium citrate, potassium chloride, and other edible salts; vitamins; minerals; and flavoring. Such additives are known in the art. See, e.g., U.S. Patent No. 3,202,514. See also, U.S. Patent No. 4,997,671. Flavorants include, for example, dairy product flavorants (e.g., milk or cheese), meat flavorants (e.g., bacon, liver, beef, poultry, or fish), oleoresin, pinacol, and the various flavorants identified in the trade by a FEMA (Flavor Extract Manufacturers Association) number. Flavorants help provide additional palatability, and are known in the art. See, e.g., U.S. Patent No. 4,997,672. See also, U.S. Patent No. 5,004,624. See also, U.S. Patent No. 5,114,704. See also, U.S. Patent No. 5,532,010. See also, U.S. Patent No. 6,379,727. The concentration of such additives in the composition typically may be up to about 5% by weight. In some embodiments, the concentration of such additives (particularly where such additives are primarily nutritional balancing agents, such as vitamins and minerals) is about 0% to about 2.0% by weight. In some embodiments, the concentration of such additives (again, particularly where such additives are primarily nutritional balancing agents) is about 0% to about 1.0% by weight.

[0066] Supplements include, for example, a feed used with another feed to improve the nutritive balance or performance of the total. Supplements include compositions that are fed undiluted as a supplement to other feeds, offered free choice with other parts of an animal's ration that are separately available, or diluted and mixed with an animal's regular feed to produce a complete feed. The AAFCO, for example, provides a discussion relating to supplements in the American Feed Control Officials, Inc. Official Publication, p. 220 (2003). Supplements may be in various forms including, for example, powders, liquids, syrups, pills, encapsulated compositions, and the like.

[0067] Treats include, for example, compositions that are given to an animal to entice the animal to eat during a non-meal time. Treats for canines include, for example, dog bones. Treats may be nutritional, wherein the composition comprises one or more nutrients, and may, for example, have a composition as described above for food. Non-nutritional treats encompass any other treats that are non-toxic. [0068] Toys include, for example, chewable toys. Toys for dogs include, for example, artificial bones. There is a wide range of suitable toys currently marketed. See, e.g.,, U.S. Pat. No. 5,339,771 (and references disclosed in U.S. Pat. No. 5,339,771). See also, e.g., U.S. Pat. No.5,419,283 (and references disclosed in U.S. Pat. No. 5,419,283). The invention provides both partially consumable toys (e.g., toys comprising plastic components) and fully consumable toys (e.g., rawhides and various artificial bones). It should be further recognized that this invention provides toys for both human and non-human use, particularly for companion, farm, and zoo animal use, and particularly for dog, cat, or bird use.

[0069] A "food" is a nutritionally complete diet for the intended recipient animal (e.g., domestic cat or domestic dog). A "nutritionally complete diet" is a diet that includes sufficient nutrients for maintenance of normal health of a healthy animal on the diet. The methods of this invention utilize compositions that are not intended to be restricted by any specific listing of proteinaceous or fat ingredients or product form. The compositions can be prepared in, for example, a dry, canned, wet, or intermediate moisture form using conventional pet food processes. In some embodiments, the moisture content is about 10% to about 90% of the total weight of the composition. In other embodiments, the moisture content is about 65% to about 75% of the total weight of the composition.

[0070] In preparing a composition for use with the methods of the present invention, any ingredient (e.g., fish oil) generally may, for example, be incorporated into the composition during the processing of the formulation, such as during and/or after mixing of other components of the composition. Distribution of these components into the composition can be accomplished by conventional means. In one embodiment, ground animal and poultry proteinaceous tissues are mixed with the other ingredients, including fish oils, cereal grains, other nutritionally balancing ingredients, special-purpose additives (e.g., vitamin and mineral mixtures, inorganic salts, cellulose and beet pulp, bulking agents, and the like); and water that is sufficient for processing is also added. These ingredients preferably are mixed in a vessel suitable for heating while blending the components. Heating of the mixture may be effected using any suitable manner, such as, for example, by direct steam injection or by using a vessel fitted with a heat exchanger. Following the addition of the last ingredient, the mixture is heated to a temperature range of about 5O ⁰ F (1O ⁰ C) to about 212 ⁰ F (100 ⁰ C). In some embodiments, the mixture is heated to a temperature range of about 7O ⁰ F (21 ⁰ C) to about 14O ⁰ F (6O ⁰ C). Temperatures outside these ranges are generally acceptable, but may be commercially impractical without use of other processing aids. When heated to the appropriate temperature, the material will typically be in the form of a thick liquid. The thick liquid is filled into cans. A lid is applied, and the container is hermetically sealed. The sealed can is then placed into conventional equipment designed to sterilize the contents. This is usually accomplished by heating to temperatures of greater than about 23O ⁰ F (HO ⁰ C) for an appropriate time, which is dependent on, for example, the temperature used and the composition.

[0071] Methods of the present invention include utilizing compositions that can be prepared in a dry form using conventional processes. In one embodiment, dry ingredients, including, for example, animal protein sources, plant protein sources, grains, etc., are ground and mixed together. Moist or liquid ingredients, including fats, oils, animal protein sources, water, etc., are then added to and mixed with the dry mix. The mixture is then processed into kibbles or similar dry pieces. Kibble is often formed using an extrusion process in which the mixture of dry and wet ingredients is subjected to mechanical work at a high pressure and temperature, and forced through small openings and cut off into kibble by a rotating knife. The wet kibble is then dried and optionally coated with one or more topical coatings which may include, for example, flavors, fats, oils, powders, and the like. Kibble also can be made from the dough using a baking process, rather than extrusion, wherein the dough is placed into a mold before dry-heat processing.

[0072] The compositions are also designed to be easier to chew. Canine and feline foods are typically formulated based on life stage (age), size, body composition, and breed. In the methods of this invention, some embodiments of the compositions address specific nutritional differences between super senior regular or small breed dogs, large breed dogs, and cats. [0073] All percentages expressed herein are on a weight by dry matter basis unless specifically stated otherwise.

[0074] As noted previously, this invention is directed, in part, to a method for enhancing the quality of life of an animal. The method comprises feeding a senior or super senior animal a composition in an amount effective to enhance alertness, improve vitality, protect cartilage, maintain muscle mass, enhance digestibility, and improve skin and pelage quality. Additionally, we now report herein our surprising discovery that the enhanced quality of life of an animal achieved by administration of the compositions of the present invention is reflected at the genomic level. While it may be that a change in expression of any one gene disclosed in the tables presented below may result in beneficial or deleterious biological effects, the data presented herein indicate that, overall, the observed expression profiles are consistent with the beneficial biological effects seen in vivo after administration of the diets disclosed herein. Specifically, gene chip data indicate that the expression of genes that encode proteins associated with or related to several biological pathways such as blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport are, for the most part, beneficially altered through administration to the animal of compositions described herein. Thus, the invention also relates to methods of measuring or characterizing the enhancement in the quality of life of an animal, particularly a senior or super senior animal, fed a composition described herein by quantitating the gene expression levels of one or more genes chosen from those disclosed in Tables 5-14 in said animal prior to and after feeding a composition disclosed herein and comparing said levels in the animal wherein an enhancement in the quality of life of said animal is reflected by a beneficial change in gene expression levels in said animal.

[0075] Quantitation of gene expression may be carried out in numerous ways familiar to one of skill in the art and include such techniques as RT PCR as well as gene chip assays and Northern blotting. Thus, it is contemplated herein that the expression levels detected may be used, for example, in methods to measure enhancement in the quality of life of an animal as disclosed herein.

[0076] There are certain age-induced changes in gene expression patterns (see, for example, P. Tollet-Egnell et al, Molecular Endocrinology, l_5{2):308-318(2001)). Without being bound by theory, such changes in gene expression patterns may be related to senescence, the aging mechanism. C-K Lee et al., Science, 285:1390-1393(1999) reported that alterations in the gene expression profile of the aging process in mice can be completely or partially prevented by caloric restriction. We have found that, surprisingly, the changes in expression of certain genes as an animal, such as a dog, ages from a healthy adult animal to a geriatric animal can be reversed by a diet of super senior dog food according to the present invention. Thus, comparing the gene expression pattern in a healthy adult dog to the gene expression pattern in a geriatric dog, one finds certain genes expressed higher ("up") in the geriatric dog while other genes are expressed lower ("down"). Surprisingly, we have found that by feeding a diet of super senior dog food according to the present invention to a geriatric dog, the gene expression pattern can be reversed. That is, comparing the gene expression pattern in a geriatric dog fed a control diet to the gene expression pattern in a geriatric dog fed a diet of super senior dog food of the present invention, one finds that certain genes are expressed higher ("up") under the control dog food regimen, while other genes are expressed lower ("down") under the control dog food regimen. The result is that the geriatric dogs under the super senior dog food diet of the present invention had their gene expression profiles altered towards that of healthy adult dogs. Comparing the list of genes that correlate in the opposite sense to the healthy adult dog/geriatric dog expression pattern, we found genes provided in Tables 15-20 below that surprisingly demonstrate that the super senior dog food of the present invention can reverse the alteration in expression that certain genes undergo as a part of the aging process. Thus, the quality of life of geriatric animals can be benefited by modifying the aging process in that the gene expression pattern of certain genes are altered towards that of a healthy adult dog from the pattern of a geriatric dog.

[0077] Accordingly, this invention is directed, in part, to a method for enhancing the quality of life of an animal comprising feeding a senior or super senior animal a composition in an amount effective to alter the gene expression pattern of certain genes (provided on Tables 15- 20 where the direction of adult vs geriatric is the same as the direction of super senior vs control) towards the pattern of a healthy adult dog form the pattern of a geriatric dog. The method enhances the quality of life of an animal by modifying the expression of genes associated with the aging process such that the gene expression pattern is altered towards that of a healthy adult animal from that of a geriatric animal.

[0078] In one aspect, this invention is directed to a method for improving the quality of life of a senior or super senior animal comprising feeding the animal a composition comprising at least about 9% by weight protein; at least about 5% by weight fat; and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid, wherein the method comprises feeding the animal the composition in an amount effective to enhance the animal's quality of life, wherein enhanced quality of life is evidenced by a change in expression of one or more genes which encode proteins associated with the aging process. As described herein, these genes are generally referred to as genes associated with the aging process, however, it should be noted that these genes specifically may be related to biological pathways chosen from , e.g., inflammation, DNA repair, cell survival, fat or cholesterol metabolism, immune regulation, protein synthesis, cell growth and cell death.

[0079] In an embodiment of this aspect, the change in expression is of one or more genes listed on Tables 15-19 and wherein the change in expression is towards the expression level in a healthy adult animal as compared to the expression level in a geriatric animal. [0080] In another embodiment of this aspect, the animal is a dog.

[0081] In another aspect, this invention is directed to a method for improving the quality of life of a senior or super senior animal comprising feeding the animal a composition comprising at least about 9% by weight protein; at least about 5% by weight fat; and at least about 0.05% by weight of at least one omega-3 polyunsaturated fatty acid, wherein the method comprises feeding the animal the composition in an amount effective to enhance the animal's quality of life, wherein enhanced quality of life is evidenced by a change in expression of one or more genes listed on Table 20 and wherein the change in expression is towards the expression level in a healthy adult animal as compared to the expression level in a geriatric animal. [0082] In an embodiment of this aspect, the animal is a dog.

[0083] It is also contemplated herein that the invention relates to methods for treating an animal suffering from disorders or disease associated with or relating to any one of more of the following biological pathways: blood clotting and platelet activation and aggregation, bone and muscle integrity, inflammatory responses, cartilage degradation and pain response, DNA damage and repair pathways, neural function, glycogen synthesis and degradation, glycolysis, gluconeogenesis, the pentose phosphate pathway, the aging process, and electron transport comprising administering to the animal an effective amount of a food composition of the present invention.

[0084] This invention is not limited to the particular methodology, protocols, and reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention. The terms "comprise", "comprises", and "comprising" are to be interpreted inclusively rather than exclusively. [0085] Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Many modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described. [0086] All patents, patent applications, and publications mentioned herein are incorporated herein by reference in their entirety. However, where there is a conflict between a definition in the present disclosure and that of a cited reference, the present disclosure controls.

EXAMPLES

[0087] This invention can be further illustrated by the following examples, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.

Example 1

[0088] A composition formulated for senior or super senior regular or small breed canines is described in Table 2.

Table 2 Ingredient Composition for Canine Regular or Small Breed Super Senior

Example 2

[0089] A composition formulated for senior or super senior large breed canines is described in Table 3. Table 3 Ingredient Composition for Canine Large Breed Super Senior

Example 3 mposition formulated for senior or super senior felines is described in Table 4.

Table 4 Ingredient Composition for Feline Super Senior

Example 4 Genomic Analysis of Control vs. Super Senior Pet Food [0091] To further characterize the nutritional benefits of the super senior pet food compositions of the present invention, gene expression profiles from animals fed the compositions compared to control animals are assayed and the results are described in detail below.

Materials and Methods: Study design:

[0092] Blood samples are drawn from 9 Beagles according to conventional methods before and after feeding for 14 days on Super Senior K9 diet (a total of 18 samples). Each sample taken after the 14-day trial is compared to its own control.

Isolation of Lymphocytes from Canine Blood Reagents:

[0093] 4ml canine blood, heparin or EDTA tubes, Hank's Balanced Salt Solution (Gibco

14175-095),HEPES buffer (Gibco 15630-080), Accu-Paque (Accurate Chemical & Scientific Corp AN3100).

Materials/Equipment:

[0094] Transfer pipettes (VWR 14670-147), 14 ml centrifuge tubes w/ caps,9" Pasteur pipettes, 1.5 ml microcentrifuge tubes (VWR 20170-038), centrifuge tube racks, microcentrifuge tube bale, waste container, Beckman Coulter Allegra 25R Centrifuge, SN AJCO IJO 15Eppendorf Centrifuge, 5417C .

Solutions:

[0095] Hank's Balanced Salt Solution (HBSS) w/ 25 mM HEPES buffer solution is made by adding 12.8 ml of HEPES buffer solution to a 500 ml bottle of HBSS. Hank's Balanced Salt

Solution and Accu-Paque need to be removed from the refrigerator and placed at room temperature at least 30 minutes before beginning the lymphocyte isolation. Both solutions should be place back in the refrigerator (4 ⁰ C) immediately following their use.

[0096] Procedure:

[0097] 1. Measure 4 ml of HB S S w/ HEPES into the correct number of 14 ml centrifuge tubes (one tube for each 4 ml draw of blood)

[0098] 2. Using a transfer pipette, transfer 4 ml blood from the Vacutainer® tubes to the

14 ml centrifuge tube containing the HBSS w/ HEPES. [0099] 3. Mix the sample well using the transfer pipette to pipette up and down for 30 seconds.

[00100] 4. Insert a 9" Pasteur pipette into each of the 14 ml centrifuge tubes. Make sure the bottom tip of the Pasteur pipette touches the bottom of the tube.

[00101] 5. Using a transfer pipette, slowly add 4 ml of Accu-Paque by running the liquid down the inside of the Pasteur pipette allowing gravity to layer the Accu-Paque under the diluted blood sample.

[00102] 6. Plug the top of the Pasteur pipette using your finger and gently remove the pipette.

[00103] 7. Centrifuge the tubes at 800 x g for 20 minutes at room temperature. For puppy blood a longer centrifugation of 45 minutes is necessary to allow for a good separation of

RBCs from WBCs.

[00104] 8. Using a transfer pipette, carefully remove the top layer to within 0.5cm of the middle opaque layer and discard.

[00105] 9. Using a new transfer pipette, carefully remove the middle opaque layer and transfer to a 1.5 ml microcentrifuge tube. Be careful not to transfer any of the bottom layers.

[00106] 10. Centrifuge the microcentrifuge tubes at 13,200 rpm for 3.5 minutes at room temperature.

[00107] 11. Carefully remove the supernatant and flash freeze the remaining pellet

(lymphocytes) in liquid nitrogen. Store the final samples at -80 ⁰ C.

RNA isolation: Reagents:

[00108] Deionized H ₂ O, Absolute ethanol (Sigma E7023), RNA Storage Solution (Ambion

7000), RNase Zap® (Ambion 9780), Buffer RLT, Buffer RWl and Buffer RPE (provided in the RNeasy Mini Kit).

Equipment/Materials:

[00109] RNeasy Mini Kit (Qiagen 74104), QIAshredder spin columns (Qiagen 79656),

PlOOO Pipetman pipette (Rainin), P200 Pipetman pipette (Rainin), 100-100 μl filtered pipette tips (USA Scientific 1126-7810), 1-200 μl filtered pipette tips (USA Scientific 1120-8810), sterile transfer pipettes (VWR 14670-147), 55 ml sterile solution basin (VWR 21007-974), 2 waste containers (one for liquid, one for tips/pipettes), 1.5 ml sterile microcentrifuge tubes (VWR 20170-038), Microcentrifuge tube rack, permanent marker, Eppendorf Microcentrifuge, model #5417C.

Procedure:

[00110] 1. Loosen the pellet in the microcentrifuge tubes by thawing slightly and then flick the tube to dislodge the pellet.

[00111] 2. Add the appropriate volume of Buffer RLT (in this case use 600 μl). Vortex or pipette to mix.

[00112] 3. Transfer sample to a QIAshredder tube to homogenize the sample. Centrifuge for 2 minutes at 14,000 rpm. Discard spin column but keep the collection tube and its contents. [00113] 4. Add one volume (600 μl) of 70% ethanol to the homogenized lysate and mix by pipetting.

[00114] 5. Apply a 600 μl aliquot of the sample to an RNeasy mini column placed in a 2ml collection tube. Close tube gently and centrifuge for 15 sec at 14,000 rpm. Discard the flow- through. Add the second 600 μl aliquot of the cell lysate to the same spin column and repeat. Discard flow-through.

[00115] 6. Reuse the collection tube from step 5. Add 700 μl Buffer RWl to the column. Centrifuge for 15 sec at 14,000rpm. Discard the flow-through and collection tube. [00116] 7. Transfer the column to a new 2 ml collection tube and pipette 500 μl Buffer RPE onto the column. Centrifuge for 15 sec at 14,000rpm to wash the column. Discard the flow-through but save the collection tube for step 8.

[00117] 8. Add another 500 ml Buffer RPE to the column. Centrifuge for 2 min at 14,000rpm to dry the membrane.

[00118] 9. Transfer the column to a new 1.5 ml collection tube. Pipette 10 μl of RNA Storage Solution directly onto the membrane. Centrifuge for lmin at 14,000 rpm to elute the RNA. Add a second volume of 5 μl of RNA Storage Solution directly to the membrane and spin for an additional minute. Store the final elution of RNA at -80 ⁰ C.

RNA probe preparation and hybridization. Reagent:

[00119] Ovation TM Biotin System vl .0 for probe preps. Protocol :

[00120] User Guide (Cat#D01002, version 10/27/04, NuGEN Technologies, Inc). The experimental procedure is followed as described in the user guide. All probe preparation starts with 50 ng of total RNA.

Gene chip Procedures:

[00121] The Genechips used for the test is the Canine Genome 2.0 Array (Affymetrix). This

Genechip contains 44,000 probe sets. Detailed sequence information for each unique probe identification number is available from the manufacturer.

Gene expression analysis:

[00122] Normalization is performed using MAS 5 provided in GCOS Affymetrix software

(version 1.2). Expression levels for the genes analyzed are indicated on the tables included in the examples below, where an upward facing arrow refers to "up regulation" or increase and a downward facing arrow indicates "down regulation" in gene expression. Similarly, in some tables, upward or downward facing arrows also indicate increases or decreases in activity of certain proteins involved in a particular pathway, and are otherwise self explanatory.

Gene list selection:

[00123] 15,411 genes are chosen for further analysis based on their "present" calls in at least

9 out of 18 samples.

[00124] Results of the gene chip analysis indicate that 1088 genes are differentially expressed between the control and Super Senior diet treated groups. The expression levels of these 1088 genes are statistically significant when grouped by 'diet'; using a parametric test where the variances is not assumed to be equal (Welch t-test). The p-value cutoff is 0.01 with no multiple testing correction. Under those selection criteria only about 154 genes would be expected to pass the restriction by chance. The genomic data is discussed in detail below.

Results:

Effect of nutrition on genes associated with pain and inflammation

[00125] Based on an analysis of the gene chip data, at the P <0.01 level, expression levels of

1,088 genes changed compared to control expression levels (10 were up regulated and the rest down regulated). At the P < 0.001 level, data indicate that expression in 35 genes is down regulated in beagles fed the super senior food. Nine of these down regulated genes are identified as related to the inflammatory and pain response. Down regulation of these genes may be predicted to result in pain relief, cartilage protection (less damage) and reduction in inflammatory responses. The compositions disclosed herein may be part of a therapeutic regimen to treat animals suffering from pain and/or inflammatory diseases. These genes and their putative role in inflammation and pain response are provided below in Tables 5-6.

Table 5: Genes involved in inflammation and pain response (P < 0.001)

% match of

Probe Best Current BLAST probe Probe Target

Genes Also Known As Annotation sequence to Sequence BLAST hit

Phosphohp IPLA2GAMMA, CfaAffx 6431 PREDICTED Cams 100 GGAGCCATGCATTT ase A2 IPLA2-2 1 S1 s at familiaπs similar to TATGACAGTCAAAC intracellular GTGGGAAAATATTC membrane-associated TTAAGGACAGAATG calcium-independent GGATCCTCGCTAAT phosphohpase A2 GATTGAAACAGCAA gamma, transcript GAAACCCTTCATGT variant 3 CCTAAGGATGGAG (LOC475880), mRNA GTTTGCTTCTGAAT

AACCCTTCAGCGCT

AGCAATGCACGAGT

GCAAATGTCTTTGG

CCTGACGTCCCATT

AGAGTGCATTGTGT

CCCTGGGCACCGG

GCGTTATGAGAGTG

ATGTGAGAAACTCT

GTGACATCTACAAG

CTTGAAAACCAAAC

TGTCTAATGTCATT

AACAGTGCTACAGA

TACAGAAGAAGTCC

ACGTAATGCTTGAT

GGTCTTTTACCTCC

TGACACCTATTTTA

GAT

Dipeptidase Putative CfaAffx 31124 PREDICTED Cams 82 197 GTGCTGCAATGCAA 2 dipeptidase 1 S1 at familiaris similar to CCTGTTAGCTAACG dipeptidase 2 TGTCCACTGTGGCA (LOC611083), mRNA GTTCCCACGCATCC

CTGCCCTGGAAGC

CCCACAGTGCTGAC

TCTCCATCCCTCAG

ATCACTTTGACTAC

ATCAGGGCAGTCAT

TGGATCCAAGTTCA

TTGGAATTGGTGGA

GATTATGATGGGGC

CAGACGTTTCCCTC

AGGGGCTGGAGGA

TGTGTCCACATACC

CAGTTCTGATAGAG

GAGTTGCTGAGGC

GTGGCTGGAGTAG

GGAAGAGCTCCAG

GGTGTCCTTCGAG % match of

Probe Best Current BLAST probe Probe Target

Genes Also Known As Annotation sequence to Sequence BLAST hit

GAAACCTACTGCGG

GTCTTTGGACAGGT

GGAACAGGTACGG

GAGGCAAGCAAGG

GGCAAAGGCCCTT

GGAGGATGAGTTC

CCGGATGAGCAGC

TGAGCAGCTCTTGC

CGCTCCGTTCTCTC

ACGTCTGCATCAGA

CACAGTACCCTGCT

CCATACCAGAAACT

AACTGAGATTTCAC

CTGAGTGGTCCCCT

AAACAGTCATTGTC

AAAATCTCTCCCCA

TCATGGCCCCAGG

CCTCATAGTTATTG

CTGCTTGT

Thromboxa Thromboxane A CfaAffx 6939 PREDICTED Cams 100 ATCGCTGGCTATGA ne synthase synthase 1 , 1 S1 s at familiaris similar to GATCATCACCAACA

Thromboxane-A CGCTCTCTTTTGCC

Thromboxane A synthase (TXA ACCTACCTCCTGGC synthase, Platelet, synthase) (TXS) CACCAACCCTGACT

(LOC482771 ), mRNA GCCAAGAGAAGCTT

Cytochrome P450, CTGGCAGAGGTGG subfamily V, ACAGCTTTAAGGAG

AAATATACGGCCCT

CYP5, CYP5A1 , TGACTACTGCAGCC Thromboxane TCCAGGAAGGCCT synthetase, TXA GCCCTACCTGGACA synthase, TXS TGGTGATTGCGGA

GACCTTGAGGATCT

ACCCCCCGGCTTTC

AGGTTCACACGGG

AGGCGGCGCGGGA

CTGCGAGGTGCGG

GGACAGCGCATCC

CCGCGGGCGCCGT

GGTGGAGGTGGCC

GTGGGCGCCCTGC

ACCGTGACCCTGA

GTACTGGCCACAAC

CGGAGACCTTCAAC

CCCGAGAGGTTCAA

GGCCGAGGCGCAG

CGACGACAGCAAC

CCTTCACCTACCTG

CCGTTCGGCGCGG

GCCCCCGGAGCTG

CCTCGGGGTGCGG

CTGGGGCTGCTGG

AGGTCAAGCTGAC

GCTGCTGCAGGTC

CTGCACCAGTTCCG

GTTCGAGGCCTGC

CCGGAGACGCAGG

TACCACTGCAGCTA

GACTCCAAATCTGC

CCTAGGTCCAAAGA

ATGGCATCTACATC

AAGATTGTCTCCCG

CT % match of

Probe Best Current BLAST probe Probe Target

Genes Also Known As Annotation sequence to Sequence

BLAST hit

Ubiquitin Ubiquitin protein CfaAffx 275 1 PREDICTED Pan 97 19626 GATTTGGCCCGTGA conjugating hgase, Ubiquitin S1_s_at troglodytes CCCTCCAGCACAAT enzyme carrier protein, LOC461941 GTTCTGCAGGTCCT

E2D 3 E2(17)KB 3, (LOC461941 ), mRNA GTTTGGGATGATAT

Ubiquitin GTTTCATTGGCAAG conjugating CCACAATTATAGGA enzyme E2-17 kDa CCTAATGACAGCCC

3, UBC4/5, ATATCAAGG

UBCH5C

NEDD8 Neural precursor Cfa 12556 1 A PREDICTED Cams 99 12473 GGAATGGGCTACTC ultimate cell expressed, 1_s_at familiaris similar to TACTCATGCAGNCA buster-1 developmentally NEDD8 ultimate AGCAGGNCCTGCA down regulated 8, buster-1 (NY-REN-18 TCAGGCCAGTGGG

Ubiquitin like antigen) AACCTGGACGAAG protein NEDD8 (LOC475542), mRNA CCCTGAAGATTCTT

CTCAGCAATCCTCA

GATGTGGTGGTTAA

ATGATTCAGATCCT

GAAACGANCAACCA

GCAAGAAAGTCCTT

CCCAGGAAAACATT

GACCAACTGGTGTA

CATGGGCTTCGAC

GCTGTGGTGGCTG

ATGCTGCCTTGAGA

GTGTTCAGGGGAAA

CGTGCAGCTGGCA

GCTCAGNCCCTCG

CCCACAACGGAGG

AACTCTTCCTCCTG

ACCTGCAGCTCTTG

GTGGAAGACTCTTC

ATCAACGCCATCCA

CGTCCCCTTCCGAC

TCCGCAGGTACCTC

TAGTGCCTCAACAG

ATGAAGATATGGAA

ACCGAAGCTGTCAA

TGAAATACTGGAAG

ATATTCCAGAACAT

GAAGAAGATTATCT

TGACTCAACACTGG

AAG

Mitogen - p38, Mitogen CfaAffx 2947 Homo sapiens 97 84946 GAGATGGAGTCCT activated activated protein 1 S1 at mitogen-activated GAGCACCTGGTTTC protein kinase 14, protein kinase 14, TGTTTTGTTGATCC kinase 14 Cytokine transcript variant 2, CACTTCACTGTGAG

(P38) suppressive mRNA (cDNA clone GGGAAGGCCTTTTC antiinflammatory MGC 34610 ATGGGAACTCTCCA drug binding IMAGE 5181064), AATATCATTC protein 1 , CSBP1 , complete cds

CSAID binding protein 1 , Stress activated protein kinase 2A,

SAPK2A , p38

MAP kinase, p38 alpha, RK, MXI2,

Cytokine suppressive antiinflammatory drug binding protein 2, CSBP2 ,

CSAID binding % match of

Probe Best Current BLAST probe Probe Target

Genes Also Known As Annotation sequence to Sequence BLAST hit protein 2

Matrix MMP 19 Cfa 4573 1 A1 Homo sapiens cDNA 48 93048 GTAGTTGATTCCTG metalloprot at FLJ38021 fis, clone GTTCGCCTTTCCTC einase 19 CTO N G2012847 TTGGGTCCCATAGG (MMP-19) TTCGAATCCCCTTC TACCTCAGTCGGGA GTACTGTCCTCCAT GGTGCTTCCCTTCC TCTCCTTAATGTGG GGAAGACCATGGG GCAATGCATGGCG CAGGACCTGCCTC CCCCAAAAGCAGTC TACTTGCTCCACGG AGAGAGAACTGGG TCCACGTGCCAGA GTCTTGCCCTTTGG CCCAGAGTAGCCT GGTCTTCATGGCTG TATGGGAGACAAGT GCCTTCTCTGCTTC TTGTTGTAGGTGAT GCTAATCTCCTTAA CCAAACCTTTGTCC CAGCCGCTAATCTG TTCTAACTCTCCCT CCTCNTGATTCTCC TGCTCAAAGTCTGT TC

Tissue TIMP-1 Cfa 3680 1 S1 Cams familiaris TIMP 994 AGATGTTCAAGGGT

Inhibitor of s at metallopeptidase TTCAGCGCCTTGGG metalloprot inhibitor 1 (TIMP1 ), GAATGCCTCGGACA einases mRNA TCCGCTTCGTCGAC

(TIMP-1 ) ACCCCCGCCCTGG AGAGCGTCTGCGG ATACTTGCACAGGT CCCAGAACCGCAG CGAGGAGTTTCTGG TCGCCGGAAACCT GCGGGACGGACAC TTGCAGATCAACAC CTGCAGTTTCGTGG CCCCGTGGAGCAG CCTGAGTACCGCTC AGCGCCGGGGCTT CACCAAGACCTATG CTGCTGGCTGTGA GGGGTGCACAGTG TTTACCTGTTCATC CATCCCCTGCAAAC TGCAGAGTGACACT CACTGCTTGTGGAC GGACCAGTTCCTCA CAGGCTCTGACAAG GGTTTCCAGAGCC GCCACCTGGCCTG CCTGCCAAGAGAG CCAGGGATATGCAC CTGGCAGTCCCTG CGGCCCCGGATGG CCTAAATCCTACTC CCCGTGGAAGCCA % match of

Probe Best Current BLAST probe Probe Target

Genes Also Known As Annotation sequence to Sequence BLAST hit

AAGCCTGCACAGTG TTCACCCCACTTCC CACTCCTGTCTTTC TTTATCCAAAA

Fatty acid Oleamide CfaAffx 7308 PREDICTED Cams 63 33333 GAAGTGGAGTAGG amide hydrolase 1 S1 x at familiaris similar to TGCCGCTGTTGCTG hydrolase Anandamide Ubiquinol-cytochrome CTGGTGTTGAATTC (FAAH) amidohydrolase c reductase complex AGAACTGTAGCGG

FAAH 1 1 kDa protein, GACATGGGGCTGG mitochondrial AGGACGAGCAAAA precursor GATGCTGACCGGG

(Mitochondrial hinge TCCGGAGATCCCAA protein) (Cytochrome GGAGGATCCCCTAA C1 , nonheme 11 kDa CAACAGTGAGAGA protein) (Complex III GCAATGCGAGCAG subunit VIII), CTGGAGAAATGTGT transcript variant 2 AAAGGCTCGGGAG

(LOC608530), mRNA CGGCTAGAGCTCT

GTGACCAGCGTGTA

TCCTCCAGGTCACA

GACAGAGGAGGAT

TGCACAGAGGAGC

TCTTTGACTTCCTG

CATGCAAGGGACC

ACTGTGTGGCCCAC

AAACTCTTTAACAG

CTTG

Table 6. Summary of down-regulated enzyme roles involved in the eicosanoid pathway (inflammatory response)

Gene Gene Expression Results in Role

Compared to

Control

Phospholipase ϊ I in arachidonic J, in 2-series inflammatory

A ₂ release from response phospholipids

Thromboxane J, Thromboxane A ₂ J, platelet aggregation, synthase vasoconstriction, lymphocyte proliferation and bronchoconstriction

J, Thromboxane B ₂ J, vasoconstriction

Dipeptidase 2 J, Leukotriene E ₄ J, component of slow-reactive substance of anaphylaxis, microvascular vasoconstrictor and bronchoconstriction

Ubiquitin J, ubiquination or J, MMP Production conjugating activation of TAKl , enzyme E2D 3 IRAK and TRAF (and NEDD8 Gene Gene Expression Results in Role

Compared to

Control ultimate buster- 1)

Mitogen ϊ J, in c-Jun promotor J, MMP Production activated protein kinase

14 (p38)

MMP- 19 ϊ J, MMP- 19 J, in T-cell derived MMP- 19 which has been implicated in rheumatoid arthritis

TIMP-I ϊ J, TIMP- 1 Deactivates MMP ' s concentration is directly related to MMP concentration

Fatty acid ϊ 1 anandmide J, pain response amide hydrolase

Effect of nutrition on genes involved in heart health and blood coagulation

[00126] At the P < 0.001 and P < 0.01 level, 12 genes are identified to be related to heart health through regulation of the eicosanoid pathway and blood coagulation pathway. The genes are responsible for blood coagulation through platelet activation and aggregation. The down regulation of these genes through nutrition can prevent inappropriate blood clotting which may result in heart or brain related disorders. The compositions of the present invention may be part of a therapeutic regimen to treat animals suffering from disorders or diseases of the blood, heart or brain. These genes and their putative role in vivo are described in Tables 7 and 8 below.

Table 7. Genes involved in heart health and blood coagulation

% match of

Best current

P- probe

Gene Probe BLAST Probe Target Seq. value sequence to annotation BLAST hit

Glycoprotein Cfa 3503 1 < 0 01 Cams familiaπs 98 57143 TGTGGGTCCGAGCTAACAGCTA

Ib S1_at glycoprotein Ib CGTGGGGCCTCTGATGGCAGG mRNA, complete ACGGCGGCCCTCTGCCCTGAG cd s CCTGGGTCGTGGGCAGGACCT

GCTAGGTACGGTGGGCGTTAG

GTACTCCAGCCACAGCCTCTGA

GGCGACGGTGGGCAGTTTGGG

GACCTTGAGAGGCTGTGATGG

GCCCTCCTATCAGGATCTTGCT

GGGGGTGGGTGGGCAGGGAG

CACAGGATTGGGGGGAGGCCT % match of

Best current

P- probe

Gene Probe BLAST Probe Target Seq. value sequence to annotation BLAST hit

TAAGCACCTTTTCTGGGTCAGA

AGCCTCCTCTCCGCATTGCATG

TGCAACCTCAGTGAAGCAGCAT

GGGCAGGGGAGCCGGACGGG

CCACCCAACAGAGCTCCTTATG

CTGCAGGAGGGGTTCACAGAC

CACTCGGACATCACCATCACCT

TGGGGGGGGTGCTTGAGGGAA

AAGCAAATTGAACAGAGCGTGA

TTCTCACGTGCAGGTACCTAAG

GGAACTGGGGAAGAGATGCAC

CAAGACGAGAGCCCTCGTCATC

CCTGGGGAGCCCAAGCCTAGG

GGTTTTCTTCCTCTTCCCGTTTA

GCATTTTCCACCATCGTATGTTA

C

Platelet CfaAffx 480 < 0 01 PREDICTED 50 AGTTTTGACCAATTCGCTCTGT glycoprotein 9 1 S1_at Cams familiaπs ACAAGGAGGGGGACACTGAGC

Vl similar to CCCACAAGCAATCTGCAGAACA glycoprotein Vl GTACTGGGCCAATTTCCCCATC

(platelet) ACCGCAGTGACTGTTGCCCACA

(LOC484303), GTGGGATCTACCGATGCTATAG mRNA CTTTTCCAGCAAGTTCCCGTAC

CTGTGGTCAGCCCCCAGCGAC

CCCCTGGAGCTTGTGGTAACAG

GTGAGGGAGATGCAGTCCAAG

CCTTTCTTCTTCAGCTCTTGCAT

ACTCTGGTGGAAGTTCCAGGG

GAGGGGCCAACAGTGCCTTCT

AGGACTATCACTGTCTCTCCAA

AGGGGTCAGACTCTCCAACTG

GTCTTGCTCACCAGCACTACAC

CAAGGGCAATCTGGTCCGGATA

TGCCTTGGAGCTGTGATTCTAA

TACTCCTGGTGGGAATTCTGGC

AGAAGATTGGCACAGCAGAAAG

AAACCCCTGTTGCTCCGGGTCA

GAGCTGTCCACAGGCCACTCC

CACCCCTCCCACAGACCCAGAA

ACCACACAGTCATCAGGATGGG

GGTCGACCAGATGGCCATAAC

CAT

Platelet CfaAffx 743 < 0 01 PREDICTED 100 TCTGGGCTGCCACGGAGGCCA glycoprotein 0 1 S1 at Cams familiaris CCAACGACTGCCCCGCAGAGT IX precursor similar to Platelet GCACCTGCCAGACCCTGGAGA glycoprotein IX CCATGGGGCTGTGGGTGGACT precursor (GPIX) GCAGGGGGCGGGGACTCAAGG

(CD42A) CCCTGCCCGCCCTGCCGGTCC

(LOC609630), ACACCCGCCACCTCCTGCTGG mRNA CCAATAACAGCCTCCGCTCCGT

GCCCCCTGGTGCCTTCGACCA

CCTGCCTGGGCTGCAGATCCT

CGACGTGATGCACAACCCCTG

GCACTGTGACTGCAGCCTCACC

TACCTGCGTCTCTGGCTGGAG

GACCACACGCCCGAGGCCTTG

CTGCAGGTCCGCTGTGCCAGC

CCCGCGCTGGCCACCACCCGG

CCGCTGGGCTGGCTGACGGGC

TACGAGCTGGGCAGCTGCGGC

TGGCAGCTACAGGCACCCTGG

ACCTA % match of

Best current

P- probe

Gene Probe BLAST Probe Target Seq. value sequence to annotation BLAST hit

Coagulation CfaAffx 149 < 0 01 PREDICTED 996008 ATCTCTCAGGCAACATCGTCTT factor XIII A 64 1 S1_s_ Cams familiaris CTACACCGGGGTCTCCAAGAC chain at similar to GGAATTCAAGAAGGAGACATTT precursor Coagulation GAAGTGACACTGGAGCCCTTGT factor XIII A CTTTCAAGAGAGAGGAGGTGCT chain precursor GATCAGAGCGGGCGAGTACAT

(Coagulation GGGCCAGCTGCTAGAGCAAGC factor XIIIa) ATACCTGCACTTCTTTGTCACA

(Protem- GCGCGTGTCAATGAGTCCAAG glutamine GATATTCTGGCCAAGCAGAAGT gamma- CCACCGTGCTGACGATCCCCC glutamyl transfer AGCTCATCATCAAGGTCCGTGG ase A chain) CGCCAAGATGGTTGGTTCTGAC (Transglutamina ATGGTGGTGACAGTTGAGTTCA se A chain), CCAATCCCCTGAAAGAAACTCT transcript variant GCGGAATGTGTGGATACACCTG

1 (LOC47871 1 ), GATGGTCCTGGAGTGATAAAGC mRNA CAATGAGGAAGATGTTCCGTGA

AATCCAGCCCANTGCCACCATA

CAATGGGAAGAAGTGTGTCGAC

CCTGGGTGTCTGGCCCTCGGA

AGCTGATAGCCAGCATGACGA

GTGACTCCCTGAGACACGTGTA

TG

Thromboxane CfaAffx 693 PREDICTED 100 ATCGCTGGCTATGAGATCATCA synthase 9 1 S1 s at 0 001 Cams familiaris CCAACACGCTCTCTTTTGCCAC similar to CTACCTCCTGGCCACCAACCCT

Thromboxane-A GACTGCCAAGAGAAGCTTCTGG synthase (TXA CAGAGGTGGACAGCTTTAAGGA synthase) (TXS) GAAATATACGGCCCTTGACTAC

(LOC482771 ), TGCAGCCTCCAGGAAGGCCTG mRNA CCCTACCTGGACATGGTGATTG

CGGAGACCTTGAGGATCTACCC

CCCGGCTTTCAGGTTCACACGG

GAGGCGGCGCGGGACTGCGA

GGTGCGGGGACAGCGCATCCC

CGCGGGCGCCGTGGTGGAGGT

GGCCGTGGGCGCCCTGCACCG

TGACCCTGAGTACTGGCCACAA

CCGGAGACCTTCAACCCCGAG

AGGTTCAAGGCCGAGGCGCAG

CGACGACAGCAACCCTTCACCT

ACCTGCCGTTCGGCGCGGGCC

CCCGGAGCTGCCTCGGGGTGC

GGCTGGGGCTGCTGGAGGTCA

AGCTGACGCTGCTGCAGGTCC

TGCACCAGTTCCGGTTCGAGG

CCTGCCCGGAGACGCAGGTAC

CACTGCAGCTAGACTCCAAATC

TGCCCTAGGTCCAAAGAATGGC

ATCTACATCAAGATTGTCTCCC

GCT

Dystrobrevin CfaAffx 155 < 0 01 PREDICTED 99 65986 GGCAACATGTCGTCCATGGAG binding 41 1 S1 s Cams familiaris GTCAACATCGACATGCTGGAGC protein 1 at similar to AGATGGACCTGATGGACATCTC isoform a dystrobrevin TGACCAGGAGGCCCTGGACGT binding protein 1 CTTCCTGAACTCCGGCGCTGAA isoform a GACAACACGGTGCCGTCTCCG

(LOC610315), GTCTCAGGGCCTGGCTCGGGG mRNA GACAGTCGGCAGGAAATCACG

CTCCGGGTTCCAGATCCCGCC

GAATCGCAAGCTGAGCCTCCTC

CCTCGCCGTGTGCCTGTCCTGA % match of

Best current

P- probe

Gene Probe BLAST Probe Target Seq. value sequence to annotation BLAST hit

GCTGGCCGCCCCGGCCCCCGG CGACGGTGAGGCCCCCGTGGT CCAGTCTGACGAGGAG

Integπn beta-7 Cfa 11961 1 < 0 01 PREDICTED 99 0909 ATTACAACGTGACTCTGGCTTT precursor A1_s_at Cams familiaris GGTCCCTGTCCTGGATGACGG similar to lntegrin CTGGTGCAAAGAGAGGACCCT beta-7 precursor AGACNAACCAGCTGCTGTTCTT

(LOC477598), CCTGGTGGAGGAGGAANCCGG mRNA AGGCATGGTTGTGTTGACAGTG

AGACCCCAAGAGAGAGGCGCG GATCACACCCAGGCCATCGTG CTGGGCTGTGTAGGGGGCATC GTGGCAGTGGGGCTGGGGCTG GTCCTGGCTTACCGGCTCTCTG TGGAAATCTACGNCCGCCGAG AATTTAGCCGCTTTGAGAAGGA GCAGAAGCACCTCAACTGGAA GCAGGAAAACAATCCTCTCTAC AGAAGCGCC integrin-linked Cfa 465 1 S < 0 01 PREDICTED 100 TGGGCGCATGTATGCACCTGC kinase 1_s_at Cams familiaris CTGGGTGGCCCCTGAAGCTCT similar to integrin GCAGAAGAAGCCTGAAGATACA linked kinase, AACAGACGCTCAGCAGATATGT transcript variant GGAGTTTTGCAGTGCTTCTGTG

1 (LOC476836), GGAACTGGTGACGAGGGAGGT mRNA ACCCTTTGCTGACCTCTCCAAC

ATGGAGATTGGAATGAAGGTGG CACTGGAAGGCCTTCGGCCTA CTATCCCACCAGGCATTTCCCC CCATGTGTGTAAGCTCATGAAG ATCTGCATGAATGAAGACCCTG CTAAGCGGCCCAAGTTTGACAT GATTGTGCCTATCCTGGAGAAG ATGCAGGACAAGTAGAGCTGG AAAGCCCTTGCCTAAACTCCAG AGGTGTCAGGACACGGTTAGG GGAGTGTGTCTCCCCAAAGCA GCAGGC

Thrombospon Cfa 21204 1 < 0 01 PREDICTED 54 83871 ATACGAATGCAGAGATTCCTAA dm 1 S1_at Cams familiaris TCAAACTGTTGATCAAAAGACT similar to GATCCTAACCAATGCTGGTGTT thrombospondin GCACCTTCTGGAACCACGGGC

1 precursor TTAAGAAAACCCCCAGGATCAC

(LOC487486), TCCTCCCTGCCTTTTCTCTGCTT mRNA GCATATCATTGTGGACACCTAG

AATACGGGACTTGCCTCGAGAC CATGCNNNNNTCCAAATCAGAC TN N N N NN GTAGCCTCTGAACGC GAAGAGAATCTTCCAAGAGCAT GAACAG

Thrombospon CfaAffx 186 < 0 01 PREDICTED 100 GAAGCCCTTGATGGATACTGTG din repeat 75 1 S1_s_ Cams familiaris AACGGGAACAGGCTATAAAGAC containing 1 at similar to CCACCACCACTCCTGTTGCCAC extracellular CACCCTCCTAGCCCTGCCCGC matrix protein 1 GATGAGTGCTTTGCCCGTCAGG isoform 1 CGCCATACCCCAACTATGACCG precursor GGACATCCTGACCCTTGATTTC

(LOC608791 ), AGCCAAGTTACCCCCAACCTCA mRNA TGCAACATCTCTGTGGAAATGG

AAGACTTCTCACCAAGCATAAA CAGATTCCTGGGCTGATCCGGA % match of

Best current

P- probe

Gene Probe BLAST Probe Target Seq. value sequence to annotation BLAST hit

ACATGACTGCCCACTGCTGTGA

CCTGCCATTTCCAGAGCAGGCC

TGCTGTGCTGAGGAGGAGAAAT

CGGCCTTCATTGCAGACTTGTG

TGGTTCCCGACGTAACTTCTGG

CGAGACTCTGCCCTCTGCTGTA

ACCTGAATCCTGGAGATGAACA

GACCAACTGCTTCAACACTTAT

TATCTGAGGAATGTGGCTCTAG

TGGCTGGAGACAAT

Thrombospon CfaAffx 166 < 0 01 PREDICTED 98 13084 TGGTTGTAGCTCCTCACTTGTC dm type 1 94 1 S1 at Cams familiaπs CAAGACCGAAGCAGCAACCAAA motif, 17 similar to lines CTGAACTTAGCCTTTGGGCTGC homolog 1 TCTTGGTAGTCACAGAAATGCC isoform 1 CACGCTTCAGTCCCCTGGGCTT

(LOC607902), CCAATGCTTCTGGACCTCTGAA mRNA CCAGCCTGTGATGTCCAAGGAA

CCCCACGTCACGCTCCAGGCT

GCTGCTGGTCTGTCTCCCCCAC

AAGCTTCTCAAAGTCTGGTAGA

TTATGACAGCTCTGATGATTCT

GAAGTAGAAGTCACAGACCAGC

ACTCAACAAACAGTAAACAAAC

ATCTTTACAGCAAGAAGCAAAG

AAGAAATTTCAGGACACAGTTA

GAACAGGTCCAGATGAAAAAGA

ACTTAGCATGGAGCCTCAATCA

AGGCCTCTGGTTCCAGAACAAT

CTAATATTAATATTCCCTTCTCT

GTTGACTGTGACATCTCCAAAG

TAGGAATATCTTACAGGACACT

GAAGTGCTTTCAGGAGCTACAG

GGTGCCATTTACCGTTTGCAGA

AAAAAAATCTTTTCCCCTATAAT

GCCACA

Angio- Cfa 8616 1 <0 001 Cams familiaris 64 77273 GCGGACTGTGTTCCAACCCCTT associated A1 s at angio-associated CAGCCGACTTGCCCCCTCCGT migratory cell migratory cell CCCTTCTCTTAAGAGACCCATC protein protein (AAMP) CCTTGGCCCCCCACCCCACCC

(AAMP) gene, complete TCACCCAGACCTGCGGGTCCC cd s TCAGAGGGGGGTCAGGCCTCT

TTCTCTTTCACCTTCATTTGCTG

GCGTGAGCTGCGGGGGTGTGT

GTTTGTATGTGGGGAGTAGGTG

TTTGAGGTTCCCGTTCTTTCCC

TTCCCAAGTCTCTGGGGGTGGA

AAGGAGGAAGAGATATTAGTTA

CAGA

Table 8: Summary of down regulated enzyme roles involved in heart health and blood coagulation

Effect of nutrition on genes involved with muscle and bone regulation

[00127] Ten down regulated genes are identified as related to body composition through regulation of bone and muscle. The genes spare muscle and bone deterioration by reducing nitric oxide production and glucocorticoid degradation of muscle. Down regulation of these genes results in a decrease in nitric oxide production and glucocorticoid response. The compositions disclosed herein may be part of a therapeutic regimen to treat animals suffering from diseases or disorders associated with or relating to muscle or bone. These genes and their putative role in muscle and bone regulation are detailed in Tables 9 and 10 below.

Table 9. Genes involved in muscle and bone regulation

% match of

Best current BLAST probe

Gene Probe P- value Probe Target Sequence annotation sequence to

BLAST hit

Capping Cfa 1044 1 0 001 PREDICTED Cams 44 87179 AGGTCCCGTAACACCGGCAT

Protein S1_at familiaris similar to F- CGCGACCGCACAGCGCCAT actin capping protein CTCCCCAGAATAAAGCCCAG beta subunit TAAACACCCCTGNNNNNNAN

(LOC478209), mRNA NNNNANNNNN CACCACGTTT

TGCTATCAGAACTCTCCTTGT

TTCCAGAGCCCGTGTGCTTT

TGTTTGCCCCAGCCCC

Calmodul Cfa 4168 1 0 01 PREDICTED Cams 52 54237 CCACCCATGGTGACGATGAC in S1_at familiaris similar to ACACATCCTGGTGGCATGCG calmodulin 1 , TGTGTTGGTTTAGCGTTGTCT transcript variant 3 GCGTTGTACTAGAGCGAAAA

(LOC480416), mRNA TGGGTGTCAGGCTTGTCACC

ATTCACACAGAAATTTAAAAA

AAAAAAAAAAAN N N N GAN AA

AAAACCTTTACCAAGGGAGC % match of

Best current BLAST probe

Gene Probe P- value Probe Target Sequence annotation sequence to BLAST hit

ATCTTTGGACTCTCTGTTTTT

AAAACCTCCTGAACCATGAC

TTGGAGCCAGCAGATTAGGC

TGTGGCTGTGGACTTCAGCA

CAACCATCAACATTGCTGATC

AAGAAATTACAATATACGTCC

ATTCCAAGTT

Dynein Cfa 4942 1 0 001 PREDICTED Cams 99 6016 ATACCTCAGAGGTCTCGTAG A1 s at familiaπs similar to CTCGTGCCCTTGCCATCCAG dynein, cytoplasmic, AGCTGGGTGGNAGAGAGCT heavy polypeptide 2, GAGAAGCAGGCTCTTTTCTC transcript variant 2 TGATACACTCGACCTGTCAG

(LOC479461 ), mRNA AACTCTTCCACCCAGACACA

TTTCTCAATGCTCTTCGCCAG

GAAACAGCAAGGGTGATGGG

CTGCTCTGTGGATAGCCTTA

AGTTTGTAGCTTCGTGGAAA

GGTCGGCTGCAAGAAGCAAA

GCTGCAGATCAAGATGGGCG

GCTTGCTTCTGGAAGGCTGC

AGTTTTGACGGGAGCCGGCT

CTCTGAAAACCACCACGATT

CTCCAAGTGTGTCACCAGTT

CTCCCTTGCTGTGTTGGCTG

GATTCCCCAGGGTGCATATG

GTCCCTATTCTCCTGACGAG

TGCATATCTCTGCCCGTGTA

CACGAGCGCTGAGAGGGAT

CGTGTGGTAGCCAACATCGA

CGTCCCGTGTGGGGGCANC

CAAGACCAGTGGATTCAGTG

TGGAGCCGCTCTGTTTCTAA

AAAA

Dynactin Cfa 1807 1 0 01 PREDICTED Cams 100 AGGACGACAAGGCTCAGGAC S1 at familiaris similar to GCAAAGTGTGAAACTGCCTT dynactin 3 isoform 2, TGTAACAGGGCAGAAGCAGC transcript variant 1 TCTGTATTGGATTCACAACCT

(LOC474750), mRNA ACCTATCTGCATTCAGGTGG

GGCTCGGAGGTCAGAGGTCT

GGCTACTTGAGGTTTGCTGT

TTGCAC

Kinesin Cfa 10496 0 01 PREDICTED Cams 99 73046 AGCCACAGCATTTCCTTTTAA 1 S1 s at familiaris similar to CTTGGTTCAATTTTTGTAGCA

Kinesin-like protein AGACTGAGCAGTTCTAAATC

KIF2 (Kιnesιn-2) CTTTGCGTGCATGCATACCT

(HK2), transcript CATCAGTG NACTGTACATAC variant 5 CTTGCCCTCTCCCAGAGACA (LOC478071 ), mRNA GCTGTGCTCACCTCTTCCTG

CTTTGTGCCTTGACTAAGGC

TTTTGACCCTAAATTTCTGAA

GCACAGCCAAGATAAAGTAC

ATTCCTTAATTGTCAGTGTAA

ATTACCTTTATTGTGTGTACA

TTTTTACTGTACTTGAGACAT

TTTTTGTGTGTGACTAGTTAA

TTTTGCAGGATGTGCCATATC

ATTGAATGGAACTAAAGTCTG

TGACAGTGGACATAGCTGCT

GGACCATTCCATCTTACATGT

A % match of

Best current BLAST probe

Gene Probe P- value Probe Target Sequence annotation sequence to

BLAST hit

Heat CfaAffx 1 10 0 01 PREDICTED Cams 100 GGTGCTACTGTTTGAAACAG

Shock 22 1 S1 s familiaπs similar to CTCTACTCTCCTCCGGCTTCT

Protein 1 at Heat shock protein CACTGGAGGATCCCCAGACT

(HSP90) HSP 90-beta (HSP CACTCCAACCGCATTTACCG

84) (Tumor specific CATGATAAAGCTAGGCCTGG transplantation 84 GCATCGATGAAGATGAAGTG kDa antigen) (TSTA) GCAGCGGAGGAACCCAGTG

(LOC611252), mRNA CTGCTGTTCCTGATGAGATC

CCTCCACTTGAGGGTGATGA

GGATGCCTCTCGCATGGAAG

AAGTC

PPIase CfaAffx 174 0 01 PREDICTED Cams 100 GACATCACCAGTGGAGACGG 0 1 S1 at familiaris similar to CACCGGCGGTATAAGCATTT Peptidyl-prolyl cis- ATGGTGAGACGTTTCCAGAT trans isomerase C GAAAACTTCAAACTGAAGCAT

(PPIase) (Rotamase) TATGGCATTGGTTGGGTCAG (Cyclophilm C) CATGGCCAACGCTGGGCCTG

(LOC481480), mRNA ACACCAACGGCTCTCAGTTC

TTTATCACCTTGACCAAGCCC

ACTTGGTTGGATGGCAAACA

TGTGGTATTTGGAAAAGTCCT

TGATGGAATGACTGTGGTCC

ACTCCATAGAACTTCAGGCA

ACCGATGGGCACG

Calcinuer Cf a 19761 0 001 PREDICTED Cams 98 83382 GAATTAACAATCTGCTTGAGC in 1 S1 at familiaris similar to CCCAAAACACTACTTATGCAC protein phosphatase TTCACTTGCCAAAAGATTTGN

3 (formerly 2B), GCAAGGTTTTGTACCCTGGT catalytic subumt, beta AAATGATGCCAAAGTTTGTTT isoform (calcineurin A TCTGTGGTGTTTGTCAAATGT beta), transcript TCTATGTATAATTGACTGTCT variant 5 GTAACATGCTGTTTNCTTCCT (LOC479248), mRNA CTGCAGATGTAGCTGCTTTC

CTAAATCTGTCTGTCTTTCTT

TAGGTTAGCTGTATGTCTGTA

AAAGTATGTTAAATTAAATTA

CTCTATCAGACGCTTGTCTGT

CTTTTGATGTAGAAGCAACTT

TGTAGCACCTTGTTTTGAGGT

NNGCTGCATTTGTTGCTGTA

CTTTGTGCAT

Protein CfaAffx 408 0 01 PREDICTED Cams 99 64664 TTCAGTTCCTGTCTCATGGC kinase C 1 S1 s at familiaris similar to CGCTCCCGGGACCATGCCAT myeloid-associated CGCCGCCACTGCCTTCTCCT differentiation marker GCATCGCTTGTGTGGCTTAT

(LOC611521 ), mRNA GCCACCGAAGTGGCCTGGA

CCCGGGCCCGTCCCGGAGA

GATCACCGGCTACATGGCCA

NTGTGCCGGGCCTGCTCAAG

GTGCTGGAGACCTTTGTGGC

CTGCATCATCTTCGCCTTCAT

CAGCAACCCCTCCCTGTACC

AGCACCAGCCGGCCCTGGA

GTGGTGTGTGGCCGTCTACT

CCATCTGTTTCATCCTGGCG

GCTGTGGCCATCCTACTGAA

CCTGGGGGACTGCACCAACA

TGCTGCCCATCTCCTTCCCC

AGTTTCCTGTCGGGCCTGGC

CCTGCTCTCCGTCCTGCTGT

ATGCCACGGCTCTGGNTCTC

TGGCCGCTCTACCAGTTCAA % match of

Best current BLAST probe

Gene Probe P- value Probe Target Sequence annotation sequence to BLAST hit

CGAGAAGTATGGTGGCCAGC

CCCGTCGGTCGAGGGATGTT

AGCTGCGCCGACAGGCACA

CCTACTACGTGTGTACCTGG

GACCGCCGCCTGGCTGTGG

CCATCCTGACAGCCATCAAC

CTGCTGGCTTACGTGGCTGA

CCTGGTGTAC

Protein Cf a 15485 0 01 PREDICTED Cams 100

Kinase C 1 A1_s_at familiaris similar to Binding protein kinase C GGAGCAGTCAGAACTAAGAC Protein binding protein 1 ATGGTCCGTTTTACTATATGA isoform b, transcript AGCAGCCACTCACCACAGAC variant 1 1 CCTGTTGATGTTGTACCGCA (LOC477252), mRNA GGATGGACGGAA

Table 10: Summary of genes affecting glucocorticoid receptors and nitric oxide production

Effect of nutrition on genes involved with DNA Damage/Protection and Neural Function

[00128] Eleven genes are identified that are related to DNA damage/protection and neural function. With regard to the latter, the genes identified are important for rebound potentiation; they are believed to have a potential role in motor learning. Interestingly, of these genes, all were down regulated except for of gamma-aminobutyric acid (GABA) A receptor, gamma 2 which was up regulated. The compositions disclosed herein may be part of a therapeutic regimen to treat animals suffering from diseases or disorders associated with or relating to DNA damage/protection and neural function. The identity of these genes and their putative role in DNA damage/protection and neural function are described in Tables 11 and 12 below.

Table 11: Genes involved in DNA damage/protection and neural function

% match of

Best current probe

Gene Probe P-value Probe Target Sequence BLAST annotation sequence to BLAST hit

Gamma- CfaAffx 26362 1 S1 < 0 01 Homo sapiens 100 CCTCTTCTTCGGATGTTT aminobutyπc at gamma- TCCTTCAAGGCCCCTAC acid (GABA) A aminobutync acid CATTGAT receptor, (GABA) A receptor, % match of

Best current probe

Gene Probe P-value Probe Target Sequence BLAST annotation sequence to BLAST hit gamma 2 gamma 2

(GABRG2), transcript variant 1 , mRNA

Calmodulin Cfa 4168 1 S1 at < 0 01 PREDICTED 52 54237 CCACCCATGGTGACGAT

Cams familiaris GACACACATCCTGGTGG similar to CATGCGTGTGTTGGTTT calmodulin 1 , AGCGTTGTCTGCGTTGT transcript variant 3 ACTAGAGCGAAAATGGG

(LOC480416), TGTCAGGCTTGTCACCA mRNA TTCACACAGAAATTTAAA

AAAAAAAAAAAAAN NNN

GANAAAAAACCTTTACC

AAGGGAGCATCTTTGGA

CTCTCTGTTTTTAAAACC

TCCTGAACCATGACTTG

GAGCCAGCAGATTAGGC

TGTGGCTGTGGACTTCA

GCACAACCATCAACATT

GCTGATCAAGAAATTAC

AATATACGTCCATTCCAA

GTT

Calcinueπn Cfa 19761 1 S1 at < 0 001 PREDICTED 98 83382 GAATTAACAATCTGCTT

Cams familiaris GAGCCCCAAAACACTAC similar to protein TTATGCACTTCACTTGC phosphatase 3 CAAAAGATTTGNGCAAG

(formerly 2B), GTTTTGTACCCTGGTAA catalytic subumt, ATGATGCCAAAGTTTGT beta isoform TTTCTGTGGTGTTTGTCA

(calcineurin A AATGTTCTATGTATAATT beta), transcript GACTGTCTGTAACATGC variant 5 TGTTTNCTTCCTCTGCA

(LOC479248), GATGTAGCTGCTTTCCT mRNA AAATCTGTCTGTCTTTCT

TTAGGTTAGCTGTATGT

CTGTAAAAGTATGTTAAA

TTAAATTACTCTATCAGA

CGCTTGTCTGTCTTTTG

ATGTAGAAGCAACTTTG

TAGCACCTTGTTTTGAG

GTNNGCTGCATTTGTTG

CTGTACTTTGTGCAT

Calcium/calmo Cfa 3884 1 S1 at < 0 01 Homo sapiens 24 10714 GGTGCTGTTCACCACAG duhn- PTEN induced TAAGTGGCCTCTCAGTG dependent putative kinase 1 TTGCTGACCAAAGTGTG protein kinase (PINK1 ), mRNA AAATCCTAGAGCTTCAG

GGGAGAGGACGTGGGG

GAAATCCGGGGCTTGAC

TTTATAATAGGATTATAG

AGATGAAAAGTACACCT

TGCTTTAGGCAACAGTT

GGGATTCCTAAGACGCA

TGTGTAAGAGCATATGT

GAAATCCCTTCCCCATT

GTTGATCTCTACTCACA

GAATTTTGTCTTTATTAT

GGTGTAAGAATCACTCT

TAAAGCCACATATTCAAT

TCAAAGCAAATACGTGT

TCTGCAGTTGCAAATGT

GTATTTAATTCTTCACAA

TTCCTGTAAG % match of

Best current probe

Gene Probe P-value Probe Target Sequence BLAST annotation sequence to BLAST hit

Adenylate CfaAffx 5462 1 S1_ < 0 01 PREDICTED 100 GAAACTCGGTCTGGTGT cyclase- s at Cams familiaris TCGATGACGTCGTGGGC associated similar to Adenylyl ATTGTGGAGATAATCAA protein 1 cyclase-associated TAGTAGGGATGTCAAAG protein 1 (CAP 1 ), TTCAGGTAATGGGTAAA transcript variant 1 GTGCCAACCATTTCCAT

(LOC475317), CAACAAAACAGATGGCT mRNA GCCATGTTTACCTGAGC

AAGAATTCCCTGGATTG

CGAAATAGTCAGTGCCA

AATCTTCTGAGATGAAT

GTCCTCATTCCTACTGA

AGGCGGTGACTATAATG

AATTCCCAGTCCCTGAG

CAGTTCAAGACCCTATG

GAATGGGCAGAAGTTGG

TCACCACAGTGACAGAA

ATTGCTGGATAAGCGAA

GTGCCACTGGGTTCTTT

GCCCTCCCCCTCACACC

ATGGGATAAATCTATCA

GGACGGTTCTTTTCTAG

ATTTCCTTTACCTTTCTG

CTCTTAAACTGCTT

Protein Cfa 6174 1 A1 at < 0 01 PREDICTED 100 AAATCTTACGAAGCCCA Phosphatase I Cams familiaris ATATGCAGGGAGTTAAC similar to protein TGAAAACTATCTTGGCA phosphatase 1A GTGAGGTTGGCACTGTT isoform 1 , GATAAAGCTGGTCCCTT transcript variant 2 CCTTTAACTGTCTTTTAG

(LOC480344), GTTGTTCTTGCCTTGTT mRNA GCCAGGAGTATTGCAGG

TAATACAGTATATTCATA

AGAATATCAATCTTGGG

GCTAAAATGCCTTGATT

CTTTGCACCTCTTTTACA

AGTCCTTACGTTGAATTA

CTAATTGATAAGCAGCA

GCTTCCTACATATAGTA

GGAGACTGCCACGTTTT

TGCTATCATGATTGGCT

GGGCCTGCTGCTGTTCC

TAGTAAGGTAT

Diazepam CfaAffx 14836 1 S1 < 0 01 PREDICTED 100 AATGGTGCCATCTTACT binding _s_at Cams familiaris GAGGGATTTTGTAGGCT inhibitor similar to GTTTTATAGATTTTCCTA peroxisomal AGCCTCTGGTTGCAGTG

D3,D2-enoyl-CoA ATAAATGGTCCAGCCAT isomerase isoform AGGAATCTCCGTCACCA

1 (LOC478706), TTCTCGGGCTATTCGAT mRNA CTTGTGTATGCTTCCGA

CAGGGCAACATTTCACA

CTCCTTTTACTCACCTG

GGCCAAAGTCCAGAAG

GATGTTCCTCCTATACTT

TTCCCAAGATAATGGGC

CAAGCCAAGGCAGCAG

AGATGCTCATGTTTGGA

AAGAAGTTAACAGCTAG

AGAAGCCTGTGCTCAAG

GACTTGTTACTGAAGTTT

TTCCCGATAGCACTTTT

CAGAAAGAAGTTTGGAC % match of

Best current probe

Gene Probe P-value Probe Target Sequence BLAST annotation sequence to BLAST hit

CAGGCTGAAAGCATATT

CAAAACTCCCCCGAAAT

ACCTTGCATATTTCCAAA

CAGAGCATCAGAAATCT

TGAGAAAGAAAAGCTAC

ATGCTGTTAACGCAGAA

GAAAACAGCGTCCTCCA

GGAAAGGTGGCTGTCA

GACGAATGCATAAATGC

AGTCATGAGCTTCTTAT

CCCGGAAGGCCAA

Tumor protein Cfa 161 1 1 A1 s at < 0 01 PREDICTED 97 90874 ATGATAGTTGCCATGCC p53 binding Cams familiaris AACCAGCTCCAGAATTA protein similar to tumor CCGCAATTATTTGTTGC protein p53 binding CTGCAGGGTACAGCCTT protein, 1 , GAGGAGCAAAGAATTCT transcript variant 4 GGATTGGCAACCCCGTG

(LOC478274), AAAACCCTTTCCACAAT mRNA CTGAAGGTACTCTTGGT

GTCAGACCAACAGCAGA

ACTTCCTGGAGCTCTGG

TCTGAGATCCTCATGAC

CGGGGGGGCAGCCTCT

GTGAAGCAGCACCATTC

AAGTGCCCATAACAAAG

ATATTGCTTTAGGGGTA

TTTGACGTGGTGGTGAC

GGATCCCTCATGCCCAG

CCTCGGTGCTGAAGTGT

GCTGAAGCATTGCAGCT

GCCTGTGGTGTCACAAG

AGTGGGTGATCCAGTGC

CTCATTGTTGGGGAGAG

AATTGGATTCAAGCAGC

ATCCAAAATACAAACAT

GATTATGTTTCTCACTAA

TACTTGGTCTTAACTGAT

TTTATTCCCTGCTGTTGT

GGAGATTGTGNTTNNNC

CAGGTTTTAAATGTGTCT

TGTGTGTAACTGGATTC

CTTGCATGGATCT

Ubiquitin CfaAffx 275 1 S1 < 0 001 PREDICTED Pan 97 19626 GATTTGGCCCGTGACCC conjugating at troglodytes TCCAGCACAATGTTCTG enzyme E2D 3 LOC461941 CAGGTCCTGTTTGGGAT

(LOC461941 ), GATATGTTTCATTGGCA mRNA AGCCACAATTATAGGAC

CTAATGACAGCCCATAT

CAAGG

NEDD8 Cfa 12556 1 A1_ < 0 001 PREDICTED 99 12473 GGAATGGGCTACTCTAC ultimate at Cams familiaris TCATGCAGNCAAGCAGG buster-1 similar to NEDD8 NCCTGCATCAGGCCAGT ultimate buster-1 GGGAACCTGGACGAAG

(NY-REN-18 CCCTGAAGATTCTTCTC antigen) AGCAATCCTCAGATGTG

(LOC475542), GTGGTTAAATGATTCAG mRNA ATCCTGAAACGANCAAC

CAGCAAGAAAGTCCTTC

CCAGGAAAACATTGACC

AACTGGTGTACATGGGC

TTCGACGCTGTGGTGGC

TGATGCTGCCTTGAGAG % match of

Best current probe

Gene Probe P-value Probe Target Sequence BLAST annotation sequence to BLAST hit

TGTTCAGGGGAAACGTG

CAGCTGGCAGCTCAGN

CCCTCGCCCACAACGGA

GGAACTCTTCCTCCTGA

CCTGCAGCTCTTGGTGG

AAGACTCTTCATCAACG

CCATCCACGTCCCCTTC

CGACTCCGCAGGTACCT

CTAGTGCCTCAACAGAT

GAAGATATGGAAACCGA

AGCTGTCAATGAAATAC

TGGAAGATATTCCAGAA

CATGAAGAAGATTATCTT

GACTCAACACTGGAAG

BCL2- CfaAffx 6742 1 S1 < 0 01 Cams familiaπs 100 GGCCCACCAGCTCTGA associated X s at BCL2-assocιated X GCAGATCATGAAGACAG protein (BAX) protein (BAX), GGGCCCTTTTGCTTCAG mRNA GGTTTCATCCAAGATCG

AGCAGGGCGAATGGGG

GGAGAGACACCTGAGCT

GCCCTTGGAGCAGGTG

CCCCAGGATGCATCCAC

CAAGAAGCTGAGCGAAT

GTCTCAAGCGCATCGGA

GATGAACTGGACAGTAA

CATGGAGTTGCAGAGGA

TGATCGCAGCTGTGGAC

ACAGACTCTCCCCGTGA

GGTCTTCTTCCGAGTGG

CAGCTGAGATGTTTTCT

GATGGCAACTTCAACTG

GGGCCGGGTTGTTGCC

CTCTTCTACTTTGCCAG

CAAACTGGTGCTCA

Table 12: Summary of genes important for rebound potentiation and DNA integrity

Effect of nutrition on genes involved with glucose metabolism

[00129] Twenty four genes associated with glucose metabolism are down regulated in animals fed the super senior diet which would suggest that these animals are utilizing fat (fat oxidation) instead of glucose as a fuel source. The compositions disclosed herein may be part of a therapeutic regime in diabetic animals and/or for obesity prevention or treatment in an animal. These down regulated genes are identified and their putative role in glucose metabolism described in detail below in Tables 13 and 14.

Table 13. Genes involved in Glucose Metabolism % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

Phosphorylase Cfa 10856 1 S1_ < 0 01 PREDICTED Cams 99 3392 GAAAGTTCACCA kinase at familiaπs similar to CTGCATGTTTTAT phosphorylase kinase GATCAGATAACT beta, transcript variant CATTGAAATGAG

2 (LOC478139), TCTTTGCTCTTTA mRNA GACTAAATTCCC

ACCTAGTACTGC

CATTAAAATGAAT

TTGCCAGCTGGT

GTGCATACTGGA

AATGAAAAGATA

CTGAAAGAATGG

AACGAATGGTGA

GCTTAACTCAGT

GGCACTGTCATA

CTGGAAAAATAC

AGTAAAATCATAA

AAACAGATCTGC

CAGCTGATGTTT

TTATTCTCAGAAA

CAGCATTGTTGA

TAATATTTTAGTA

TACAGAGCTACT

GTACAATTTTTAC

CTTGNAAACATG

ACTGTGGTTTTG

TATTTGTGTTGAC

TTTAGGGGTTGG

GATAAAATNCAG

TATAATATATACC

TTATCAAACNTTT

TCTTTGAGCTCTT

ACTAAAAATATG

GCATGCATAAGA

TTGTTCAGAAGA

GTAGACTGTTAA

CCTAGTTTGTA

Phosphorylase Cfa 10412 1 A1_ < 0 01 PREDICTED Cams 99 36306 CTTCCAGAGCTG s at familiaris AAGCTGGCCATT phosphorylase, GATCNAAATTGA glycogen, liver, CAATGGCTTCTT transcript variant 1 CTCTCCCAAGCA (PYGL), mRNA GCCTGNCCTCTT

CAAAGATTTAATC

AATATGCTATTTT

ATCATGACAGGT

TTAAAGTCTTCG

CAGACTATGAAG

CCTATGTCAAGT

GTCAAGAAAAAG

TCAGCCAGCTGT

ACATGAATCCAA

AGGCCTGGAACA

CAATGGTACTCA

AAAACATAGCTG

CCGCAGGGAAGT

TCTCTAGTGACC

GAACAATTAAGG

AATATGCCAGGG

ACATCTGGAACA

TGGAACCTTCAG

ATCTCAAGATTTC

CCTATCCAATG % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

Glycogen Cfa 913 1 A1 < 0 01 PREDICTED Cams 9949622 GACTCCACCGGA synthase kinase at familiaris similar to GGCAATTGCACT

3 Glycogen synthase GTGTAGCCGTCT kιnase-3 beta (GSK-3 GCTGGAGTATAC beta), transcript ACCAACTGCCCG variant 1 ATTGACACCACT (LOC478575), mRNA GGAAGCTTGTGC

ACATTCATTTTTT

GATGAATTAAGG

GACCCAAATGTC

AAACTACCAAAT

GGGCGAGACACA

CCTGCACTCTTC

AACTTCACCACT

CAAGAACTGTCA

AGTAATCCACCT

CTAGCTACCATC

CTTATTCCTCCTC

ATGCTCGGATTC

AAGCAGCTGCTT

CAACCCCTACAA

ATGCCACAGCAG

CCTCAGATGCTA

ATGCCGGAGACC

GTGGACAGACGA

ACAATGCCNCTT

CTGCATCAGCTT

CTAACTCCACCT

GAACAGTCCCGA

GCAGCCAGCTGC

ACAGGAAGAACC

ACCAGTTACTTG

AGTGTCACTCA

Calmodulin Cfa 4168 1 S1_a < 0 01 PREDICTED Cams 52 54237 CCACCCATGGTG t familiaris similar to ACGATGACACAC calmodulin 1 , ATCCTGGTGGCA transcript variant 3 TGCGTGTGTTGG

(LOC480416), mRNA TTTAGCGTTGTCT

GCGTTGTACTAG

AGCGAAAATGGG

TGTCAGGCTTGT

CACCATTCACAC

AGAAATTTAAAAA

AAAAAAAAAAAN

NNNGANAAAAAA

CCTTTACCAAGG

GAGCATCTTTGG

ACTCTCTGTTTTT

AAAACCTCCTGA

ACCATGACTTGG

AGCCAGCAGATT

AGGCTGTGGCTG

TGGACTTCAGCA

CAACCATCAACA

TTGCTGATCAAG

AAATTACAATATA

CGTCCATTCCAA

GTT

Protein Kinase C CfaAffx 408 1 S1 < 0 01 PREDICTED Cams 99 64664 TTCAGTTCCTGT s at familiaris similar to CTCATGGCCGCT myeloid-associated CCCGGGACCATG differentiation marker CCATCGCCGCCA

(LOC611521 ), mRNA CTGCCTTCTCCT % match of

Best current BLAST probe

Gene Probe P-Value annotation sequence to Probe Target Seq. BLAST hit

GCATCGCTTGTG

TGGCTTATGCCA

CCGAAGTGGCCT

GGACCCGGGCC

CGTCCCGGAGAG

ATCACCGGCTAC

ATGGCCANTGTG

CCGGGCCTGCTC

AAGGTGCTGGAG

ACCTTTGTGGCC

TGCATCATCTTC

GCCTTCATCAGC

AACCCCTCCCTG

TACCAGCACCAG

CCGGCCCTGGA

GTGGTGTGTGGC

CGTCTACTCCAT

CTGTTTCATCCT

GGCGGCTGTGG

CCATCCTACTGA

ACCTGGGGGACT

GCACCAACATGC

TGCCCATCTCCT

TCCCCAGTTTCC

TGTCGGGCCTGG

CCCTGCTCTCCG

TCCTGCTGTATG

CCACGGCTCTGG

NTCTCTGGCCGC

TCTACCAGTTCA

ACGAGAAGTATG

GTGGCCAGCCCC

GTCGGTCGAGG

GATGTTAGCTGC

GCCGACAGGCAC

ACCTACTACGTG

TGTACCTGGGAC

CGCCGCCTGGCT

GTGGCCATCCTG

ACAGCCATCAAC

CTGCTGGCTTAC

GTGGCTGACCTG

GTGTAC

Protein Kinase C Cfa 15485 1 A1 < 0 01 PREDICTED Cams 100 GGAGCAGTCAGA Binding Protein s at familiaris similar to ACTAAGACATGG protein kinase C TCCGTTTTACTAT binding protein 1 ATGAAGCAGCCA isoform b, transcript CTCACCACAGAC variant 11 CCTGTTGATGTT (LOC477252), mRNA GTACCGCAGGAT

GGACGGAA

Hexokmase 3 Cfa 19125 2 S1 < 0 01 Macaca fascicularis 7670683 TAATGACTGCCA at testis cDNA, clone ACTCACTGTTTGT

QtsA-14856, similar to TGGAGTTATATG human receptor CAGAAATAAAGN associated protein 80 CCAAGTCTTCAG

(RAP80), mRNA, AAACAGGCTTCA

RefSeq GGATGCCCTCAC NM 016290 3 CAGGGATGGAAG

AGGCAGGCTGCA

GCAAAGAGATGC

AGAGTTCCCTTG

CACATCTCGACT % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

TAAATGAGTCTC

CCATCAAGTCTTT

TGTTTCCATTTCA

GAAGCCACAGAT

TGCTTAGTGGAC

TTTAAAAAGCAAC

TTAACGTTCGGC

AAGGTAGTCGGA

CACGGACCAAAG

CAGGCAGAGGAA

GAAGGAGAAAAC

CCTGAATTTCTA

GGGTCCAGACAC

CCGACAAAACCA

TTAGCAATAGGG

GTGGGCCGTGTC

ATTAAGTCTTAGT

GGCTTCTGTTTC

ATTGTTGAACAA

GTTTTTTGGCCC

NGCAGTTTTCAC

CACCAGCACCAA

CTCAGCATTCTT

GTTTTGATGTTTT

CTATAAGCTATAC

AGACAATTGTGT

ATAGTATTCTGTT

TTATAACAGTCTG

GATTCACTT

Fructose 1 ,6 CfaAffx 26135 1 < 0 01 PREDICTED Cams 100 AGTGGCGCTGTG bisphosphatase S1 s at familiaris aldolase A, TGCTGAAAATTG transcript variant 1 GGGAACACACTC (LOC479787), mRNA CCTCAGCCCTTG

CGATCATGGAAA

ATGCCAACGTTC

TGGCCCGTTAT

Glyceraldehyde AFFX- < 0 01 Cams familiaris 100 AGCTCACTGGCA

3-phosphate Cf_Gapdh_3_at glyceraldehyde-3- TGGCCTTCCGTG dehydrogenase phosphate TCCCCACCCCCA dehydrogenase ATGTATCAGTTGT (GAPDH), mRNA GGATCTGACCTG

CCGCCTGGAGAA

AGCTGCCAAATA

TGACGACATCAA

GAAGGTAGTGAA

GCAGGCATCGGA

GGGACCCCTCAA

AGGCATCCTGGG

CTACACTGAGGA

CCAGGTGGTCTC

CTGTGACTTCAA

CAGTGACACCCA

CTCTTCCACCTT

CGACGCCGGGG

CTGGCATTGCCC

TCAATGACCACT

TTGTCAAGCTCA

TTTCCTGGTATG

ACAATGAATTTG

GCTACAGCAACC

GGGTGGTGGAC

CTCATGGTCTAC

ATGG % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

Glucose 6- Cfa 19351 1 S1_ < 0 01 Homo sapiens cDNA 15 1 1194 GAATGTGTTGGC phosphate at FLJ30869 fis, clone AGACTGAGGCCC dehydrogenase FEBRA2004224 CCCATGTTTTTAA

TGCGCACTGGGG

ACAACCATCTAA

GGTCTAGAAACT

TTTGGACCATAG

GAAAGATAGGTT

TATGGTCCTCTT

CCAGATGCAGCC

CTAGGAGAGCAT

TCCCATGGGGTC

TCTGGATCCCTT

TCNTTGCTCTGT

GAGGCTCTGTGA

CCACCTTTTGNN

NTGNNGGGGGC

AGGGGGNCTTCC

TCAGCTCCGCCT

CCAGTGCCCCCA

GGTCCCCCACGG

CTCACAGTCCNT

GAAAATTCAGAG

CTGCCCTGTAAG

GATTTTGTCCACT

GGGCAATTCAGA

TATACTTCGATAT

CCCTGAGAAAGA

AGAGGCAGCAGC

AAACACTCCCNA

GGGCATCTGTCT

CAGNANTCTCTC

NTTGNATGAGAC

AGAAGCCTACTT

TTCAGAAANCTTA

TCANGGNTACTT

TATAAGAAACTTT

TTTTTTTTT N CTA

AAATCAGACAAA

AGGTGGCTTNTG

CATATTCTTNATT

AATAACTGTGTCT

TTGTCTCCTCTG

CTTAACTTTAGGA

Enolase CfaAffx 30133 1 < 0 01 PREDICTED Cams 97 72257 GGTACATCACGC S1 s at familiaris similar to CTGATCAGCTGG

T21 B10 2b, transcript CTGACCTCTACA variant 1 AGTCCTTCATCA

(LOC479597), mRNA GGGACTACCCAG

TGGTGTCTATCG

AAGACCCCTTCG

ACCAGGATGACT

GGGAAGCTTGGC

AGAAATTCACTG

CCAGCGCTGGAA

TCCAGGTGGNGG

GGGANGATCTCA

CCGTGACCAACC

CAAAGCGGATTT

CCAAGGCTGTGG

GCGAGAAATNGT % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

GCAACTGCCTCC

TGCTTAAAGTGA

ACCAGATTGGCT

CTGTGACCGAGT

CTCTTCAGGCGT

GCAAGCTGGCCC

AGTCCAATGGGT

GGGGCGTCATG

GTGTCGCATCGC

TCCGGGGAGACC

GAAGATACCTTC

ATCGCTGACCTG

GTGGTGGGANTC

TGCACTGGGCAG

ATCAAGACGGGT

GCACCATGCAGA

TCTGAGCGCTTG

GCCAAGTACAAC

CAGATCCTCAGA

ATTGAAGAGGAA

CTGGGTAGCAAG

GCCAAGTTCGCC

GGCAGAAGCTTC

AGAA

Lactate Cfa 300 1 S1 at < 0 01 PREDICTED Cams 97 99427 ATCTGACCTGTT dehydrogenase familiaπs similar to L- ACTCAAGTCGTA lactate ATATTAAAATGGC dehydrogenase A CTAAGAAAAAAA chain (LDH-A) (LDH CATCAGTTTCCTA muscle subunit) AAGTTACACATA

(LDH-M) GGAATGGTTCAC

(Proliferation-inducing AAAACCCTGCAG gene 19 protein), CTATGTCCTGAT transcript variant 1 GCTGGATGAGAC

(LOC476882), mRNA CTGTCTTGTGTA

GTCCTAAATTGG

TTAACGTAATATC

GGAGGCACCACT

GCCAATGTCATA

TATGCTGCAGCT

ACTCCTTAAACC

AGATGTGTATTTA

CTGTGTTTTGTAA

CTTCTGATTCCTT

CATCCCAACATC

CAACATGCCTAG

GCCATCTTTTCTT

CTTCAGTCACAT

CCTGGGATCCAA

TGTATAAATTCAA

TATTGCATGTATT

GTGCATAACTCT

TCTA

Citrate lyase Cfa 10361 2 S1_ < 0 01 PREDICTED Cams 9849624 AGTATGCCAGAT at familiaris similar to CGGAACCTTTTT citrate lyase beta like CCCATTTACAGTT

(LOC476974), mRNA CATGTTAATCCAA

TTTTTTTTATTAT

CTCACTGGCCAG

TTATTCCTTTAAA

AATGAACTTCCTT

CTTTTTGATTCCA

AGCTTATGATTTT % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

ACTGCTCATTAAT

GTGTTACAAATAT

GCACTTAATGATT

TCACAGGGAGAT

AAAATAGTGAAG

AGAGATGGGCTG

AGGGGCTGTTAG

GACTTTAATGAAA

CAGATCTTTCCC

GAATATTTCTCCC

TTCACATTTCTCA

CATTAGATGTTTC

CCACATTGTTCTA

CTCCACACTATA

AATAATTTTAAGG

CCAATCTTAAAAA

ATGGTAGTTAAG

TGAAGGGGTTGT

GTTTATTTCACTA

GAAATCTGATAA

AACGAGAGATGA

CATAGAAAAAGT

TATCATTTTTGTT

CATACAGATGGC

TTCTAAAAATAAA

TCTTCAAAACTGA

TTACTTTTAACCT

CCACCTCCCAAA

ATGAAACATCCC

TACATTTGAACTG

CTAGGTGAGAAC

TCTGAAAGCCCT

CATCC

Glycerol kinase CfaAffx 21204 1 < 0 01 PREDICTED Cams 100 GGGTACATCCTA S1 s at familiaπs similar to TGGCTGCTATTT glycerol kinase CGTCCCCGCGTT isoform 2, transcript TTCAGGGTTATAT variant 8 GCACCTTACTGG (LOC480872), mRNA GAGCCCAGTGCA

AGAGGGATCATC

TGTGGGCTCACT

CAATTCACCAATA

AATGCCATATTG

CTTTTGCTGCATT

AGAAGCTGTTTG

TTTCCAAACCCG

GGAGATTTTGGA

TGCCATGAACCG

AGACTGCGGAAT

TCCACTCAGTCA

TTTGCAGGTAGA

TGGAGGAATGAC

CAACAACAAAATT

CTTATGCAACTA

CAAGCAGACATT

CTATATATCCCA

GTAGTGAAGCCC

TCGATGCCAGAA

ACAACTGCCCTG

GGAGCTGCCATG

GCAGCCGGGGC

TGCGGAGGGAGT

TGGTGTTTGGAG

TCTTGAACCCGA % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

GGATCTGTCAGC AGTCACGATGGA GCGATTTGAACC CCAGATCAATGC TGAGGAAAGTGA AATTCGTTACTCT ACATGGAAGAAG GCTGTGATGAAG TCAGTGGGCTGG GTTACAACTCA

Transketolase CfaAffx 13684 1 < 0 01 Homo sapiens 86 53846 GAAGATCTGGCC S1 s at transketolase ATGTTTCGGTCC

(Wernicke-Korsakoff ATCCCCACTGCT syndrome), mRNA ACGATCTTTTACC

(cDNA clone CAAGTGACGGGG

MGC 15349 TGTCAACAGAGA

IMAGE 4310396), AGGCGGTGGAAT complete cds TAGCAGCCAATA

CAAAGGGCATCT

GCTTCATCCGGA

CCAGCCGCCCAG

AAAACGCCATCA

TCTATAACAACAA

TGAGGATTTCCA

AATCAAACAAGC

CAAGGTGGTCCT

GAAGAGCAAGGA

TGACCAGGTGAC

TGTGATTGGGGC

CGGAGTGACCCT

ACATGAGGCCTT

GGCTGCTGCTGA

ACTGCTGAAGAA

AGAGAAGATCAA

CATTCGTGTGTT

GGACCCCTTCAC

CATCAAGCCCCT

GGACAGAAATCT

CATTCTCGAAAG

CGCCCGTGCGAC

CAAGGGCAGGAT

CGTCACCGTGGA

GGACCATTACTA

TGAAGGTGGCAT

AGGTGAGGCAGT

GTCCTCTGCCTT

GGTGGGTGAGC

CTGGCATCACCG

TCTCCCGCCTTG

CAGTTGGTGAGG

TACCAAGAAGCG

GGAAGCCAGCTG

AGCTGCTGAAGA

TGTTTGGCATTG

ACAGGGACGCCA

TCGCACAAGCTG

TGAGGGACCTTG

TCGCCAA

Ribulose Cfa 13084 1 A1 < 0 01 Homo sapiens SLIT- 57 79468 CCCCAAGGAGAT phosphate 3- s at ROBO Rho GTPase GAGGAGCGATGA epimerase activating protein 2 CCCCAGCAACAG

(SRGAP2), mRNA GAANAACAGCCC ACTGAAGGGCTG % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

GTGTGTGTGTNC

TTCACGTGCCAG

AAGAGAAGTTTA

GATCCTCCCAGG

GGAATCGCAATG

TTGTGGCGTCCT

GACTTGTATGTC

ACGTTTTGTGTAA

AAATGGTATATTC

TTTAAAATAGTGT

TGATAACTGGAA

TATTGTATGTATG

CTTGGAGATGCT

TTGTGTGAACCT

AAGACTGTCACT

CAACAGATGTTG

GATTGGG

Ribose 5- Cfa 335 2 S1 at < 0 01 PREDICTED Cams 100 AGCCTTTCTACT phosphate familiaris similar to GACCCTGCAAGA isomerase ribose 5-phosphate GTGGAGCGTGTT isomerase A (ribose CACCTTGAACCC

5-phosphate CCAGCGTGCAGC epimerase) TGAGGTAGACAT

(LOC475755), partial GCCTCTCCAGGA mRNA GCCTTTGCCTTA

ATGCATCTGTGC

CAGACAGACGGC

TGG

Cytochrome c CfaAffx 4942 1 S < 0 01 PREDICTED Cams 100 GGCAGTTTGAAA oxidase 1 s at familiaris similar to ATAAAGTTCCAG polypeptide VIIa- cytochrome c AGAAACAAAAGC hver/heart, oxidase, subunit 7a 3 TATTTCAGGAGG mitochondrial (LOC611 134), mRNA ATAATGGAATTC precursor CAGTGCATCTAA

AGGGTGGAGTAG

CTGATGCCCTCC

TGTATAGAGCCA

CTATGATGCTTA

CAGTTGGTGGAA

CAGCATATGCCA

TGTATCAGCTAG

CTGTGGCTTCTT

TTCCCAAGAAGC

A

Cytochrome c Cfa 15065 1 S1 < 0 01 PREDICTED Cams 99 75961 GGTCCGCAGTCG oxidase subunit at familiaris similar to TTCTGTGCGGTC

VIII liver form Cytochrome c oxidase ATGTCTGTGCTG polypeptide Vlll-hver, GTGCCGCAGCTG mitochondrial CTGAGGGGCCTA precursor ACAGGCCTCACC

(Cytochrome c CGGCGGCTCCC oxidase subunit 8-2) GGTGCATCGTGC

(LOC476040), mRNA CCAGATCCATTC

CAAGCCGCCGC

GGGAGCAGCTC

GGGACCATGGAT

GTTGCCGTTGGG

CTCACCTNCTGC

TTCCTGTGTTTCC

TCCTGCCATCGG

GCTGGGTCCTGT

CACACCTGGAGA % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

GCTACAAGAAGC

GGGAGTGAAGG

GGGCTGTCCTGT

CCCTCACCCTGT

GACCTGACCACC

CCTGGCCTGTCC

TGATCATGTCTG

CTGCATTCCTGG

CCGGCCTTCCAT

GGATCATGTCCT

TCAATTACAGTG

ACCTCTTCTACA

GTCATGACCTCT

TGATTTCTCCATG

GTGACATCCTGG

GACCAAACATAT

TGGTTTATAA

Ubiquinolύcytoch Cfa 1425 2 A1 < 0 01 PREDICTED Cams 27 18053 CTTATGCATTCCT rome c t familiaπs similar to TCCAAAATTGGA reductase Ubiquinol- TCATTTAGGTCAA cytochrome-c ATTATTTGATGTT reductase complex AAATCATAAGTTT core protein 2, TCATTTGCTTACA mitochondrial TTTACGATATCAG precursor (Complex III CGTCAGCTACGG subunit II), transcript AATCAATCTGCT variant 1 GAAGGACCGTGG (LOC479815), mRNA CTGGCGGCGTGT

ACGATCCAGCAA

CCAGCGCCTGG

GACCCGACTTCA

TCCAGGAACCCC

TCAGAAGACTCC

ACTGACATTAGG

AAGACTCATAAG

AACCTTACAAGA

AAAAGTATCAAC

CCCATCAAAACG

GCAGAAAAGAAA

CATATCTTGTTAT

TAGTAGCTGAAA

TTCCATTTTCTAC

ATGTTGCCATAC

CTTATAAAAACTA

CACTAAGCTACG

CTTAAGGAAATA

CATTTTCTTAAAT

AAATTAGAATTGA

AACCAATTTTTAA

GTAAATCTAGGG

NTTCAATTTATTC

TCATTGNGTNTT

GTTTCTGGTGCA

ATCATGAANAAC

AGCATNCTATTAA

CCAACCTTGGTC

CCATGTACATAA

ATP synthase CfaAffx 3186 1 S < 0 01 PREDICTED Cams 98 57651 AATTGGGACTGT 1 s at familiaris similar to GTTTGGGAGCCT ATP synthase, H+ CATCATTGGTTAT transporting, NCCAGGAATCCC mitochondrial FO TCTCTGAAGCAA complex, subunit c CAGCTCTTCTCC % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit isoform 2a precursor TACGCCATTCTG (LOC477595), mRNA GGCTTTGCCCTC

NCGGAGGCCATG

GGGCTTTTTTGC

CTGATNGTGGCC

TTTCTCATCCTCT

TNGCCATGTGAA

GGAGTCGTCTCC

ACCTCCCATAGG

TCTTTCTCCCATG

TCTTGTCTGCCC

TGTATGCCCTGT

ATGTTCCTTTTCC

TATACCTCCCCA

GGCAGCCTGGG

GAAAGTGGTTGG

CTCAGGGTTTGA

CA

NADH- Cfa 4415 1 S1_ < 0 01 PREDICTED Cams 98 20789 GGTGACTTTGGA ubiquinone t familiaris similar to CGTCCGTTCCTG oxidoreductase NADH-ubiquinone CTCTGTGGAGGC oxidoreductase NNTGCTTCGTTC

MLRQ subunit CGGGCCTTGCG

(Complex I-MLRQ) GCAACTCGGTNT

(CI-MLRQ) TTCCTTCCCCTG (LOC477682), mRNA CGCGGGAGACCT

CTGCCACAACCA

TGTTACGCCAGA

TCATCGGTCAGG

CCAAGAAGCATC

CGAGCTTGATCC

CCCTCTTCATATT

TATTGGGGCAGG

AGGTACTGGAGC

AGCGCTGTATGT

ATTGCGCTTGGC

ATTGTTCAATCCA

GATGTTAGTTGG

GATAGGAAGAAT

AACCCAGAACCT

TGGAACAAACTG

GGTCCCAATGAT

CAATACAAGTTCT

ACTCAGTGAATG

TAGATTACAGCA

AACTGAAGAAAG

AAGGTCCAGACT

TCTAAATGAAATG

TTTCACTATAAAG

CTGCTTAGAATG

AAGGTCTTCCAG

AAGCCATCCGCA

CAATTTTCCACTT

ATCCAGGAAATA

TTTCCCCTCTAAA

TGCACGAAATCA

TGTTGGTGTATT

GTGTTGGGGTTT

ACACTNNANNAN

TAAATATCTGAAA

CTTGANANGTGT

CACTATTTAATGC

TGAAAATTTGCTC

TGAACTTTA % match of

Best current BLAST probe

Gene Probe P-Value Probe Target Seq. annotation sequence to BLAST hit

Facilitated Cfa 1370 1 A1_a < 0 01 Homo sapiens cDNA 23 95833 TTGGAAGGATGG glucose t FLJ44038 fis, clone ATGCTTGCCCCA transporter/ TESTI4028880, highly GGTCATGGACAC

Glucose similar to Glucose CTCCACAAATCA transporter-like transporter type 3, TCTAGTTTCCCA protein III brain GTATTTTTATAAA

(GLUT3) TGGAGATTGGGC

TCCATGACACTTT

ACTTGGTCTTCC

TTCTTACATAGGT

TTTTTGATTACCC

TTTCTCTCCTTGG

TGCTTATATACTT

AAGACCCTTTAG

CCAAACCCTTGC

CAATGACAGTAT

TTCAGTCACTAG

TTCTCACTGTTTC

CTCTGATCATTG

AGCCTTTGGAAA

AAAAATCTCACA

GAGCTTATATGT

AATGGGGCTTGG

TTGAACAGATGA

CTTCCTGTAACT

GCACCTCTACTT

TTGGCTTCTCAA

AAACAGTGGGTT

GGCAGTAATGCA

GCGTGGAAGTTT

TCCCATTTCTCA

GTGAC

Table 14. Summary of Genes involved in Glucose Metabolism

Example 5

Comparison of Gene Expression Profiles of Genes Associated with the Aging Process: Healthy Adult Dogs versus Senior Dogs in comparison to Control Diet versus Super Senior Diet

[00130] A dog's gene expression profile changes as the dog ages from being an adult dog to becoming a geriatric (senior) dog. This is true for genes associated with numerous biological pathways such as, e.g., glucose metabolism, blood clotting and bone and muscle integrity but also with regard to genes that have been associated with the aging process, or senescence, in general. With regard to this class of "aging" associated genes, we have found that, by feeding senior dogs a super senior diet according to the present invention, the gene expression profile of certain of these genes in lymphocytes tends to move towards the profile of an adult dog from that of a geriatric dog. Thus, geriatric dogs fed a super senior diet according to the present invention can have their genetic profile altered to resemble more closely the genetic profile of a healthy adult dog.

[00131] The results displayed below in Tables 15-20, show that genes normally altered with the aging process can be regulated through nutritional strategies targeted at common aging changes. Specifically, the results show that, when fed a super senior diet, generally the expression levels of the genes in lymphocytes move in the opposite direction as that of the expression level in a healthy adult animal compared to the expression level in a geriatric animal. That is, when the expression level in a healthy adult animal is high compared to a geriatric animal (i.e., "down regulated" in the geriatric animal), the super senior fed geriatric animals generally also have higher expression level (altered to be "up regulated" ) as compared to a geriatric animal fed the control diet. Similarly, when the expression level in a healthy adult animal is low compared to a geriatric animal ("up regulated" in the geriatric animal), the super senior fed geriatric animals generally also have lower expression level (altered to be "down regulated") as compared to a control diet fed geriatric animal. Thus, expression levels of aging related genes in geriatric dogs may be beneficially altered when the geriatric dog is fed a super senior diet of the present invention and thus the dogs may therefore lead lives of improved quality.

Table 15. Aging Genes Associated With Inflammation

Table 16. Genes Associated With DNA Repair/Cell Survival

Table 17. Aging Genes Associated With Fat/Cholesterol Metabolism

Table 18. Aging Genes Associated With Protein Synthesis

Table 19. Aging Genes Associated With Cell Growth/Death Table 20. Genes Altered With Age and Super Senior Diet with Unknown Functions