Compositions and methods for reducing biological age of adult animals using spermidine

Abstract

The compositions and methods reduce the biological age of an adult animal and / or reduce the rate of increase in the biological age of an adult animal. More specifically, the present disclosure relates to administering formulations comprising an effective amount of spermidine, alone or in combination with a dietary regimen such as a standard diet, caloric restriction, elderly diet, or high protein diet. The preparation can simultaneously reduce the biological age of tissues, organs or physiological systems in adult animals in need; or treating, preventing or delaying the onset of organ disease, or the decline of organ function, or a condition associated therewith, in an adult animal in need thereof.

Description

TECHNICAL FIELD

[0001] The present disclosure relates generally to compositions and methods for reducing the biological age of an adult animal and / or reducing the rate of increase of the biological age of an adult animal. More specifically, the present disclosure relates to administration of a formulation comprising an effective amount of spermidine, alone or in combination with a dietary regimen, such as a diet in which the protein is 18% to 60% protein / dry matter (w / w) for dogs and 26% to 60% protein / dry matter (w / w) for cats. The formulation can simultaneously reduce the biological age of a tissue, organ or physiological system in an adult animal in need thereof; or treat, prevent or delay the onset of an organ disease, or the decline of organ function, or a condition associated therewith, in an adult animal in need thereof. BACKGROUND

[0002] It is well known that chronological age is a major indicator of overall health status, with an increase in chronological age being associated with a decrease in health status. However, depending on genetics, nutrition and lifestyle, individuals can age more or less quickly than their chronological age.

[0003] Thus, chronological age can not always reflect the rate of aging or the risk of decrease in health status of an individual. On the other hand, the biological age of a certain individual, based on e.g. clinical biochemistry and cellular biology measurements, can differ compared to other individuals of the same chronological age.

[0004] Highly digestible and high quality protein diets are generally recommended based on the chronological age of a dog. For example, it can be recommended that a dog be switched to a senior diet at around 7 or 8 years of age. However, determining the biological age of a dog compared to its chronological age increase can allow for the determination of additional nutritional regimens to provide to the animal.

[0005] Thus, there is a need for methods and compositions that effectively reduce the biological age of an adult animal having an increased biological age compared to its chronological age and conditions associated therewith. SUMMARY

[0006] Thus, in a general embodiment, the present disclosure provides a method for reducing the biological age of an adult animal in need thereof and / or for reducing the rate of increase of the biological age of an adult animal in need thereof, the method comprising: feeding the adult animal a composition comprising an effective amount of spermidine. As detailed by the experimental data shown later herein, the present inventors surprisingly found that spermidine induces a reduction in biological age. This reduction in biological age occurred regardless of the diet administered in combination with the spermidine.

[0007] The present disclosure also provides a method for reducing the biological age of a tissue, organ or physiological system in an adult animal in need thereof, the method comprising feeding the adult animal a composition comprising an effective amount of spermidine.

[0008] The present disclosure also provides a method for treating, preventing or delaying the onset of an organ disease, or the decline of organ function, or a condition associated therewith, in an adult animal in need thereof, the method comprising feeding the adult animal a composition comprising an effective amount of spermidine.

[0009] Suitably, the method can comprise selecting and / or applying a composition comprising an effective amount of spermidine to an animal upon determining that the biological age of the animal is greater than its chronological age. The increased biological age can be in a tissue, in an organ or in a physiological system, such as the immune, gastrointestinal, urinary, muscular, cardiovascular and / or nervous system.

[0010] Suitably, improving the biological age of an animal can refer to a reduction in the difference between the biological age and the chronological age of the animal, wherein the biological age of the animal is greater than its chronological age. Alternatively, deterioration of the biological age of an animal can refer to an increase in the difference between the biological age and the chronological age of the animal, wherein the biological age of the animal is greater than its chronological age.

[0011] Suitably, improving the biological age of an animal can refer to a reduction in the rate of change between the biological age and the chronological age of the animal, wherein the biological age of the animal is greater than its chronological age. For example, for each 1 year increase in chronological age, the biological age of the animal can have increased by 1.5 years.

[0012] Suitably, while the compositions of the present invention can be effective for animals based on their chronological age, they can be particularly effective when applied to animals having an increased biological age compared to their chronological age. Thus, the present method can advantageously benefit animals having an increased likelihood of responding or an improved magnitude of response to the compositions of the present invention.

[0013] The composition comprising spermidine can be part of or administered with a dietary regimen. The dietary regimen can be a diet in which the protein is 18% to 60% protein / dry matter (w / w) for dogs and 26% to 60% protein / dry matter (w / w) for cats.

[0014] An advantage of one or more embodiments provided by the present disclosure is to improve a condition in an animal, an aging animal or an aging human.

[0015] Another advantage of one or more embodiments provided by the present disclosure is to increase the survivability of an aging individual.

[0016] Another advantage of one or more embodiments provided by the present disclosure is to increase the activity of an animal.

[0017] Additional features and advantages are described in, and will be apparent from, the following DETAILED DESCRIPTION and the Figures. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The amounts of protein, carbohydrate, and fat of the first diet fed to mice and the second diet used in the examples are shown.

[0019] Figure 2 The effect of administering a composition comprising an effective amount of spermidine in the first diet and the second diet, respectively, on biological age is shown. Biological age was estimated by analyzing DNA methylation using the intervention muscle clock. DETAILED DESCRIPTION Definitions

[0020] Some definitions are provided below. Nonetheless, definitions can be located in the “EMBODIMENTS” section below, and the heading “DEFINITIONS” above does not mean that such disclosure in the “EMBODIMENTS” section is not a definition.

[0021] All percentages expressed herein are by weight of the total composition, unless expressed otherwise. As used herein, “about,” “approximately” and “substantially” shall be understood to mean within a range of numbers, for example, within -10% to +10% of the value in question, preferably within -5% to +5% of the value in question, more preferably within -1% to +1% of the value in question, most preferably within -0.1% to +0.1% of the value in question. All numerical ranges herein should be understood to include integers or fractions within the range. Additionally, these numerical ranges should be construed to support a claim limitation involving any number or subset of numbers within the range. For example, a disclosure of from 1 to 10 should be understood to support a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, etc.

[0022] As used in this disclosure and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. For example, reference to “a component” or “a method” includes a plurality of such “components” or “methods.”

[0023] The term "comprising / including" will be interpreted as inclusive rather than exclusive. Similarly, the terms "comprising / including" and "or" should be considered inclusive unless the context explicitly prohibits this interpretation. However, the compositions and methods disclosed herein may not contain any elements not explicitly disclosed herein. Therefore, the disclosure of embodiments using the term "comprising / including" includes disclosures of embodiments that "consist substantially of the specified components or steps" or embodiments that "consist of the specified components or steps."

[0024] The terms “at least one of X and Y” and “and / or” used in the context of “at least one of X and Y” and “X and / or Y” respectively should be interpreted as “X without Y” or “Y without X” or “both X and Y”. Where used herein, the terms “example” and “such as” (especially when followed by a list of terms) are merely exemplary and illustrative and should not be considered exclusive or comprehensive.

[0025] As used herein, “related to,” “associated with,” and “connected to” mean that they occur simultaneously, preferably that they are caused by the same underlying condition, more preferably that one of the specified conditions is at least indirectly caused by the other specified condition, and most preferably that one of the specified conditions is directly caused by the other specified condition.

[0026] The terms “food,” “food supplement,” “food product,” and “food composition” mean a product or composition intended for ingestion by an individual (such as a human) and to provide that individual with at least one nutrient. The compositions of this disclosure (including the various embodiments described herein) may comprise, consist of, or consist substantially of the elements disclosed herein, and any additional or optional ingredients, components, or elements described herein or that may be used in a dietary supplement.

[0027] "Prevention" includes reducing the risk, incidence, and / or severity of a condition or disorder. The term "treatment" includes both preventative or averting treatment (preventing and / or delaying the development of a target pathological condition or disorder) and curative, therapeutic, or disease-modifying treatment, including therapeutic measures that cure, delay, alleviate symptoms of a diagnosed pathological condition or disorder and / or halt its progression; and treatment of patients at risk of or suspected of having the disease, as well as treatment of patients who are ill or diagnosed with a disease or medical condition. The term "treatment" does not necessarily mean that a subject is treated until fully recovered. The term "treatment" also refers to health maintenance and / or promotion in individuals who do not have a disease but may be susceptible to unhealthy conditions. The term "treatment" is also intended to include intensifying or otherwise enhancing one or more major preventative or therapeutic measures. As a non-limiting example, treatment may be administered by a patient, caregiver, physician, nurse, or other healthcare professional.

[0028] The relative term “reduction” etc. refers to the effect of a composition containing spermidine (disclosed herein) relative to a composition without spermidine or with a reduced level of spermidine but otherwise identical.

[0029] As used in this article, the “effective amount” for prevention or treatment is the amount used to prevent an individual’s defect, treat their disease or medical condition, or more generally, the amount used to alleviate an individual’s symptoms, manage the progression of their disease, or provide them with nutritional, physiological, or medical benefits.

[0030] "Animals" includes, but is not limited to, mammals, including but not limited to rodents; aquatic mammals; domesticated animals, such as dogs and cats; farm animals, such as sheep, pigs, cattle and horses; and humans.

[0031] In the human context, the term "elderly person" means someone who is at least 55 years old from birth, preferably 63 years or older, more preferably 65 years or older, and most preferably 70 years or older. In the human context, the term "middle-aged or older person" or "elderly individual" means someone who is at least 45 years old from birth, preferably 50 years or older, more preferably 55 years or older, and includes elderly individuals.

[0032] For other animals, "middle-aged or elderly" or "senior individual" means having exceeded 50% of the average lifespan of its particular species and / or breed. An animal is considered "senior" if it exceeds 66% of its average life expectancy, preferably exceeding 75%, and more preferably exceeding 80%. Senior cats or dogs are at least approximately 5 years old from birth. Older cats or dogs are at least approximately 7 years old from birth.

[0033] Chronological age can be defined as the amount of time elapsed from the subject's birth to a given date. Chronological age can be expressed in years, months, days, etc. In some implementations, the animal is a dog and can be at least about 2 years old. Suitably, the dog can be at least about 2 years old, at least about 3 years old, at least about 4 years old, at least about 5 years old, at least about 6 years old, at least about 7 years old, at least about 8 years old, at least about 9 years old, or at least about 10 years old.

[0034] The biological age of a specific tissue, organ, or physiological system can be determined using a DNA methylation map, which contains or is composed of methylation sites of genes preferentially or specifically expressed from that tissue, organ, or physiological system. Gene classification by specific tissue, organ, or physiological system is publicly available at, for example, Gene Ontology (http: / / geneontology.org / ), the KEGG pathway database (https: / / www.genome.jp / kegg / ), or MSIgDB (https: / / www.gsea-msigdb.org / gsea / msigdb / index.jsp).

[0035] The term "composition" can refer to food, beverage, dietary supplement, complete nutrition or oral nutritional supplement (ONS) or medical food composition or mixtures thereof.

[0036] As used herein, “complete nutrition” comprises a full range of macronutrients (proteins, fats, and carbohydrates) and micronutrients in sufficient quantities to serve as the sole source of nutrition for the animal receiving the composition. From such complete nutrition compositions, an individual can obtain 100% of its nutritional needs.

[0037] As used herein, the term "unit dosage form" refers to a physically discrete unit suitable for use as a unit dose in human and animal subjects, each unit containing a predetermined amount of the composition disclosed herein, associated with a pharmaceutically acceptable diluent, carrier, or mediator, sufficient to produce the desired effect. The specifications of a unit dosage form depend on the specific compound used, the effect to be achieved, and the pharmacodynamics associated with each compound in the host. Embodiments

[0038] One aspect of this disclosure is a method for reducing the biological age of an adult animal in need and / or reducing the rate of increase in the biological age of an adult animal in need. The method includes feeding the adult animal a composition containing an effective amount of spermidine. This method may include determining the biological age of the animal (e.g., a human or dog) using any suitable method to determine its DNA methylation profile.

[0039] Compositions containing an effective amount of spermidine and / or functional derivatives can be administered to animals, such as humans (e.g., aging individuals), or pets at a therapeutically effective dose. This therapeutically effective dose can be determined by those skilled in the art and will depend on many factors known to those skilled in the art, such as the severity of the condition and the individual's weight and general condition.

[0040] Non-limiting examples of suitable forms of spermidine include spermidine trihydrochloride, spermidine phosphate hexahydrate, spermidine phosphate hexahydrate, and L-argininoyl-3,4-speridine. Malt extract is rich in spermidine. Therefore, some embodiments of the composition include malt extract and / or enriched malt extract in which at least a portion of spermidine is provided.

[0041] In certain embodiments, the method involves increasing plasma spermidine levels in an individual to, for example, levels ranging from 50 nmol / L to 6000 nmol / L plasma, preferably from 100 nmol / L to 6000 nmol / L plasma. The method may include daily administration of spermidine in the weight range of 0.05 mg to 1 g per kg body weight, preferably 1 mg to 200 mg per kg body weight, more preferably 5 mg to 150 mg per kg body weight, even more preferably 10 mg to 120 mg per kg body weight, or most preferably 40 mg to 80 mg per kg body weight. In some embodiments, the method may include administration of 10 mg–100 mg of spermidine per serving, for example, about 16 mg per food serving or about 80 mg per supplement or snack serving.

[0042] The composition is preferably administered to the individual for at least two days per week, more preferably at least three days per week, and most preferably all seven days per week; for a duration of at least one week, at least one month, at least two months, at least three months, at least six months, or even longer. In some embodiments, the composition is administered to the individual for multiple consecutive days, for example, at least until a therapeutic effect is achieved. In one embodiment, the composition may be administered to the individual daily for at least 30, 60, or 90 consecutive days.

[0043] The above application examples do not require uninterrupted, continuous daily application. Instead, brief interruptions may be allowed during application, such as interruptions of two to four days during the application period. The ideal duration of application of the composition can be determined by those skilled in the art.

[0044] In a preferred embodiment, the composition is administered to the individual orally or via the gastrointestinal tract (e.g., tube feeding). For example, the composition may be administered to the individual in the form of a beverage, capsule, tablet, powder, or suspension.

[0045] The composition can be any kind of composition suitable for human and / or animal consumption. For example, the composition may be selected from food compositions, dietary supplements, nutritional compositions, nutritional products, powdered nutritional products reconstituted with water or milk before consumption, food additives, pharmaceuticals, beverages, and drinks. In one embodiment, the composition is an oral nutritional supplement (ONS), a complete nutritional formula, a pharmaceutical product, a medical product, or a food product. In a preferred embodiment, the composition is administered to an individual in the form of a beverage. The composition may be stored in powder form in sachets and then suspended in a liquid such as water for use.

[0046] In one embodiment, the composition comprises a protein source. The composition may comprise a mixture of one or more types of proteins, such as one or more (i) peptides, (ii) long amino acid chains, or (iii) amino acids in free form; and the mixture is preferably formulated to achieve a desired amino acid profile / content.

[0047] At least a portion of the protein may be derived from: animal or plant sources, such as bovine milk proteins, one or more of milk proteins, such as milk protein concentrates or milk protein isolates; caseinates or casein, such as micellar casein concentrates or micellar casein isolates; or whey proteins, such as whey protein concentrates or whey protein isolates. Additionally or alternatively, at least a portion of the protein may be a plant protein, such as one or more of soybean protein or pea protein.

[0048] In one embodiment, the composition comprises a carbohydrate source. Any suitable carbohydrate may be used in the composition, including but not limited to starch (e.g., modified starch, amylose, tapioca starch, corn starch), sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, xylitol, sorbitol, or combinations thereof.

[0049] The carbohydrate source is preferably no more than 50% of the energy of the composition, more preferably no more than 36% of the energy of the composition, and most preferably no more than 30% of the energy of the composition. The composition may have a high protein:carbohydrate energy ratio, for example greater than 0.66, preferably greater than 0.9, and more preferably greater than 1.2.

[0050] In one embodiment, the composition comprises a fat source. The fat source may include any suitable fat or mixture of fats. Non-limiting examples of suitable fat sources include vegetable fats (such as olive oil, corn oil, sunflower oil, high-oleic sunflower oil, rapeseed oil, canola oil, hazelnut oil, soybean oil, palm oil, coconut oil, blackcurrant seed oil, borage oil, lecithin, etc.), animal fats (such as milk fat); or butyrate sources in the form of compounds combining these. In some embodiments, the fat source comprises less than 20% of the composition.

[0051] In a preferred embodiment, the composition further comprises an autophagy inducer selected from urolithin (e.g., urolithin A, B, or D), rapamycin, Torin 1, valproic acid, polyphenols (e.g., resveratrol), caffeine, metformin, 5'AMP-activated protein kinase (AMPK) activators, L-type calcium channel inhibitors, and mixtures thereof. Non-limiting examples of suitable autophagy inducers are palmitic acid, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), verapamil, nifedipine, diltiazem, piperazine phenothiazine derivatives (e.g., trifluoperazine), ketones (e.g., β-hydroxybutyrate, ketone salts, or ketone ester derivatives), and mixtures thereof.

[0052] In some embodiments, the composition is administered to an individual in a single dosage form, i.e., all compounds are present in a single product, which is provided to the individual in combination with a dietary regimen.

[0053] A dietary plan can be a diet, a dietary program, a supplement or a supplement program, or a combination of a diet and supplements, or a combination of a diet and multiple supplements.

[0054] The dietary interventions or dietary products described herein can be any suitable dietary program, such as a standard diet, a calorie-restricted diet, an old person's diet, a high-protein diet, a phosphorus diet, a potassium-supplemented diet, a polyunsaturated fatty acid (PUFA) supplemented diet, an antioxidant supplemented diet, a vitamin B supplemented diet, a liquid diet, a selenium-supplemented diet, or a diet supplemented with carnitine, a branched-chain amino acid or its derivative, or any combination thereof.

[0055] Dietary interventions can be determined based on the dog's baseline maintenance energy requirement (MER). Appropriately, MER can be the amount of food required to maintain a stable dog's weight (a change of less than 5% over three weeks).

[0056] Appropriately, a calorie-restricted diet may comprise approximately 50%, 55%, 60%, 65%, 75%, 80%, 85%, or 90% of a dog's MER (Mild Menstrual Scale). Appropriately, a calorie-restricted diet may comprise approximately 60% or 75% of a dog's MER.

[0057] In one embodiment, the composition has a protein / energy ratio of greater than 6 g protein / 100 kcal, preferably greater than 9 g protein / 100 kcal. In one embodiment, on a dry matter basis, the protein content is between 18% and 60% (w / w) of the composition.

[0058] The dietary regimen may include foods, supplements, and / or beverages that contain nutrients and / or bioactive agents that mimic the benefits of calorie restriction (CR) without restricting daily calorie intake. For example, foods, supplements, and / or beverages may contain functional ingredients with similar CR benefits. Suitablely, foods, supplements, and / or beverages may contain autophagy inducers. Suitablely, foods, supplements, and / or beverages may contain fruits and / or nuts (or extracts thereof). Suitable examples include, but are not limited to, pomegranate, strawberry, blackberry, camu camu, walnut, chestnut, pistachio, and pecan. Suitablely, foods, supplements, and / or beverages may contain probiotics, with or without fruit or nut extracts.

[0059] The methods described herein can be used to i) reduce the biological age of an animal and / or reduce the rate of increase in the biological age of an animal, or ii) reduce the biological age of a tissue, organ, or physiological system, and iii) treat, prevent, or delay the onset of any organ disease or organ dysfunction or related symptoms in an animal.

[0060] Individuals in need can be elderly animals or elderly humans. Individuals in need can be aging humans or aging animals. Individuals in need can have a biological age greater than their chronological age. Furthermore, the rate of change of an individual in need between biological ages can be greater than the rate of change with respect to their chronological age.

[0061] In one embodiment, the increased biological age can occur in tissues, organs, or physiological systems such as the immune, gastrointestinal, urinary, muscular, cardiovascular, and / or nervous systems. In a preferred embodiment, the tissue is the liver, kidney, or skeletal muscle. Non-limiting examples of such muscles include one or more of the following: vastus lateralis, gastrocnemius, tibialis, soleus, extensor muscles, digitorum longus (EDL), biceps femoris, semitendinosus, semimembranosus, gluteus maximus, extraocular muscles, facial muscles, or diaphragm.

[0062] In one implementation, the animal in need lacks spermidine in one or more of its tissues.

[0063] Those skilled in the art will understand that they are free to combine all the features of the invention described herein without departing from the scope of the invention disclosed herein. Examples

[0064] The following non-limiting examples illustrate the basic concepts of the embodiments disclosed herein.

[0065] The present invention will now be further described by way of examples, which are intended to help those skilled in the art to implement the invention, without limiting the scope of the invention in any way. Example 1 Materials and Methods Animal Care

[0066] All animal experiments were conducted in accordance with the International Guidelines for Biomedical Research Involving Animals, established by the Council of International Organizations for Medical Sciences, and the following animal welfare guidelines. Eighteen-month-old mice were kept in a temperature- and humidity-controlled environment with a 12:12-h light-dark cycle. Mice had access to nesting and enrichment materials, and free access to water and food. Mouse Treatment and Sample Collection

[0067] In the experiment, mice were fed (i) a first diet, (ii) a first diet supplemented with spermidine, (iii) a second diet, or (iv) a second diet supplemented with spermidine. Figure 1 The differences between diet 1 and diet 2 fed to mice are shown. Diet 1 consisted of 16% fat, 20% protein, and 64% carbohydrates. Diet 2 consisted of 16% fat, 60% protein, and 24% carbohydrates. These amounts are percentages of total energy consumed. Animals found dead or euthanized at the humane endpoint due to pain or physical suffering were excluded from the analysis. At the end of treatment, mice were euthanized with isoflurane after a 2-hour fast. The gastrocnemius muscle was dissected, and samples were rapidly frozen in liquid nitrogen and stored at -80°C. DNA Extraction

[0068] DNA was extracted from 100 mg of muscle using the QIAGEN DNeasy Blood and Tissue Kit (catalog number: 69506) and following the manufacturer's recommendations. DNA was quantified using DropSense technology (from Unchained Labs). Methylation Detection

[0069] 500 ng of DNA was converted to bisulfite using the Zymo EZ DNA Methylation Kit (catalog number: D5001) following the manufacturer's recommendations. 200 ng of the converted DNA was then used for the Infinium HD methylation assay, following the manufacturer's recommendations. DNA methylation data were generated using the following custom array: HorvathMammalMethyl40 (catalog number: 20027399), from Illumina, with the consent of the Clock Foundation (Torrance, CA), which developed these arrays. The iScan scanning array from Illumina was used. Data Analysis

[0070] To calculate biological age, raw data were analyzed using an algorithm (clock) developed by the Clock Foundation. An interventional muscle clock, trained on tissue-specific data from mice undergoing caloric restriction, was used. This clock is based on methylation analysis of different CpGs and demonstrated robust, full-fledged age predictive power. Results obtained for each sample corresponded to biological age in years. Data were plotted and analyzed using GraphPad Prism 9. Plain one-way ANOVA was performed, followed by Dunnett multiple comparisons, to test the effects of age and spermidine supplementation compared to their respective controls. Results

[0071] The results showed that mice fed a spermidine-containing diet-1 had a lower biological age compared to mice fed an untreated diet-1. Furthermore, mice fed a spermidine-containing diet-2 had a lower biological age compared to mice fed a spermidine-containing diet-1. Surprisingly, daily administration of spermidine at a dose of 17.5 mg / kg / day for 12 weeks significantly reduced the biological age of mice fed both diet-1 and diet-2. Figure 2 As shown, treatment with spermidine resulted in a decrease in muscle biological age as measured by the intervention muscle clock.

Claims

1. A method for reducing the biological age of an adult animal in need and / or for reducing the rate of increase in the biological age of an adult animal in need, the method comprising: The adult animals were fed a composition containing an effective amount of spermidine.

2. A method for reducing the biological age of tissues, organs, or physiological systems in an adult animal in need, the method comprising feeding the adult animal a composition containing an effective amount of spermidine.

3. The method according to claim 2, wherein the tissue, organ or physiological system is the immune, gastrointestinal, urinary, muscular, cardiovascular and / or nervous system.

4. The method of claim 2, wherein the tissue is deficient in spermidine.

5. The method according to any one of claims 2 to 4, wherein the tissue is skeletal muscle.

6. A method for treating, preventing, or delaying the onset of organ disease, organ dysfunction, or related symptoms in an adult animal in need, the method comprising feeding the adult animal a composition containing an effective amount of spermidine.

7. The method according to any of the preceding claims, wherein the animal in need has an increased biological age compared to its actual age.

8. The method according to any of the preceding claims, wherein the increased biological age is determined by the DNA methylation profile of the adult animal.

9. The method according to any of the preceding claims, wherein the animal is an aged animal.

10. The method according to any of the preceding claims, wherein the animal is a pet animal.

11. The method according to any of the preceding claims, wherein the animal is a human.

12. The method according to any of the preceding claims, wherein the composition is selected from food compositions, dietary supplements, nutritional compositions, nutritional products, powdered nutritional products reconstituted with water or milk before consumption, food additives, pharmaceuticals, beverages, dry or wet pet foods, and combinations thereof.

13. The method according to any of the preceding claims, wherein the composition is part of or administered with a dietary regimen.

14. The method of claim 13, wherein the dietary regimen comprises a diet in which the protein content for the dog is 18% to 60% protein / dry matter (w / w).

15. The method of claim 13, wherein the dietary regimen comprises a diet in which the protein content for the cat is 26% to 60% protein / dry matter (w / w).

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