Limited (INTERNMENT) calorie restriction methods to provide health benefits to animals

Abstract

The present invention provides methods for treating, preventing, or delaying the onset of organ disease in animals and for reducing biological age in adult animals using intermittent portion-restricted diets, which methods may involve feeding the animals two different diets with different calorie contents in specific ratios to achieve such benefits.

Description

【Technical Field】 【0001】 Cross - reference to Related Applications 【0001】This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 120,777, filed on December 3, 2020, the entire disclosure of which is incorporated herein by reference. 【0002】 [Background Art] [Technical Field] 【0002】The present invention generally relates to methods for providing health benefits to animals by using certain intermittent calorie - restricted diets, and more particularly to methods for using feeding patterns for providing such health benefits. 【0003】 Description of Related Art 【0003】Long - term calorie restriction (CR) without malnutrition has been shown to improve both mean and maximum lifespan, extend healthspan (life without chronic diseases), and prevent, delay, or reduce the incidence of many chronic diseases, including cardiovascular disease, cancer, diabetes, hypertension, stroke, dementia, Alzheimer's disease, and Parkinson's disease. Unfortunately, it is very difficult to practice CR for the above - mentioned health benefits because it requires reducing calorie intake per day over a lifetime. 【0004】

[0004] Several methods for replicating CR are known in the art. For example, every-other-day fasting can extend life (Goodrick et al., Mech Ageing Dev 1990;55:69-87), but every-other-day fasting for a lifetime is also very difficult in practice. Fasting for four consecutive days every two weeks can also extend life (Sogawa H, Kubo C. Mech Ageing Dev 2000;115:61~71), but this approach is also very difficult for most people and animals. Simulated fasting therapy (FMD) has been shown to reduce biomarkers and risk factors for aging, diabetes, cancer, and cardiovascular disease (Wei et al., Sci Transl. Med, 2017, 9:waai8700). FMD is low in calories, sugar, and protein, but high in unsaturated fats. Furthermore, people need to consume FMD for five consecutive days each month for at least three months in order to see any effects. 【0005】

[0005] Therefore, there is a need for new methods to deliver the health benefits associated with long-term calorie restriction without requiring a daily reduction in calorie intake. 【0006】 [Overview of the prefecture]

[0006] A method for treating, preventing, or delaying the onset of an organ disease or organ dysfunction or related condition in an animal, comprising: feeding the animal a calorie-maintaining diet containing calories that meet the animal's maintenance energy requirements during a calorie-maintaining period; and feeding the animal a calorie-reducing diet containing approximately 40% to approximately 60% of the calories contained in the calorie-maintaining diet during a calorie-reducing period, wherein the ratio of the calorie-maintaining period to the calorie-reducing period is approximately 4:3. 【0007】

[0007] A method for treating, preventing, or delaying the onset of an organ disease or impaired organ function or a related condition in an animal, comprising: feeding the animal at the discretion of the animal during a discretionary period; and feeding the animal a calorie-reduced diet containing approximately 40% to approximately 60% of the animal's maintenance energy requirement during a calorie-reduced period, wherein the ratio of the discretionary period to the calorie-reduced period is approximately 4:3. 【0008】

[0008] A method for reducing the biological age of an adult animal or the biological age of an organ in an adult animal, comprising: feeding the adult animal a calorie-maintaining diet containing calories that meet the maintenance energy requirements of the adult animal during a calorie-maintaining period; and feeding the adult animal a calorie-reducing diet containing approximately 40% to approximately 60% of the calories that meet the maintenance energy requirements of the adult animal during a calorie-reducing period, wherein the ratio of the calorie-maintaining period to the calorie-reducing period is approximately 4:3. 【0009】

[0009] A method for reducing the biological age of an adult animal or the biological age of an organ in an adult animal, comprising: feeding the adult animal at the discretion of the animal during a discretionary period; and feeding the adult animal a calorie-reduced diet containing about 40% to about 60% of the calories required to meet the animal's maintenance energy needs during a calorie-reduced period, wherein the ratio of the discretionary period to the calorie-reduced period is about 4:3. 【0010】

[0010] Other and further objects, features and advantages of the present invention will be readily apparent to those skilled in the art. 【0011】 [Modes for carrying out the invention] definition

[0011] The term “animal” means a human or other animal from which the present invention can be used to treat, prevent or delay the onset of organ diseases or impaired organ function or conditions, or to reduce the biological age of animals including birds, cattle, dogs, horses, cattle, chickens, mice, sheep, and pigs, or to reduce the biological age of organs in animals. 【0012】

[0012] The term “companion animal” refers to domestic animals such as cats, dogs, rabbits, guinea pigs, ferrets, hamsters, mice, gerbils, horses, cows, goats, sheep, donkeys, and pigs. In one embodiment, companion animal may refer to dogs and / or cats. 【0013】

[0013] The term “therapeutic dose” means an amount of a compound disclosed herein that (i) treats or prevents a particular disease, condition, or disorder; (ii) alleviates, improves, or eliminates one or more symptoms of a particular disease, condition, or disorder; or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder described herein. 【0014】

[0014] The terms “to treat,” “to treat,” and “treatment” encompass both preventive treatment and palliative treatment. 【0015】

[0015] The term “elderly” means that an animal is old enough to exceed 50% of the average lifespan of its particular species and / or breed within that species. For example, if the average lifespan of a given breed of dog is 10 years, then any dog ​​belonging to that breed that is older than 5 years would be considered “elderly” for the purposes of this specification. Furthermore, for example, if the average lifespan of a breed of cat is 15 years, then any cat belonging to that breed that is older than 7.5 years would be considered “elderly” for the purposes of this specification. In one embodiment, the compositions and methods disclosed herein relate to older animals, for example, older dogs or older cats. Animals such as dogs and cats are considered old in the last 25% of their lifespan. As described herein, the lifespan of a dog or cat varies by its size and / or breed, and an older dog or cat may be determined based on the above calculation, but using the number 75% so that the age threshold exceeds 75% of the average lifespan. 【0016】

[0016] The terms “intermittent period” or “intermittently” mean a first period and a second period that occur repeatedly at predetermined intervals and have the same or different durations. For example, a routine intermittent period involves performing one action on one day and a different action on the next day, and in some cases repeating a pattern of periods of two or more days as many times as needed or desired. Similarly, one action, such as feeding an animal, may be performed for a week, and a second action, such as feeding the animal a different diet, may be performed for two weeks, and this cycle may be repeated for a year or throughout the life of the animal. The same applies to periods of multiple days, weeks, months, quarters, years, etc., for example, daily, two days, three days, four days, five days, six days, weekly, two weeks, three weeks, monthly, two months, quarterly, four months, five months, half a year, yearly, etc. 【0017】

[0017] The term "in conjunction with" means, in accordance with the present invention, that for a first period, an animal is fed a first diet containing calories that meet the animal's maintenance energy requirements, and for a second period, an animal is fed a second diet containing calories that do not meet the animal's maintenance energy requirements, and that different compounds, compositions, or other active substances are administered to the animal (1) together in the form of a diet composition, or (2) separately, at the same or different frequencies, using the same or different routes of administration, at approximately simultaneous or periodic intervals. "Periodicly" means that a particular active substance is administered in an acceptable dosage schedule for that particular animal, and that the food is appropriately and routinely fed to the animal for that particular animal. "Approximately simultaneously" generally means that the food and the active substance are administered at the same time or within about 72 hours of each other. "In conjunction with" specifically includes administration schemes in which an active substance is administered for a predetermined period and the diet composition of the present invention is administered indefinitely. 【0018】

[0018] The term “complete and balanced” means, when referring to a food composition, a food composition that, based on the recommendations of recognized authorities in the field of animal nutrition, contains all known essential nutrients in appropriate amounts and proportions, and therefore can serve as the sole source of dietary intake to sustain life or promote production without the need for additional nutritional supplements. Nutritionally balanced pet food and animal food compositions, such as complete and balanced food compositions formulated according to the standards as of January 1, 2020, as defined by the Association of American Feed Control Officials (AAFCO), are widely known and widely used in the art. 【0019】

[0019] The term “single package” means that the components of the kit are physically associated with or in one or more containers and are considered as one unit for the purposes of manufacture, distribution, sale, or use. Containers include, but are not limited to, bags, boxes, cartons, bottles, packaging of any kind, design, or material, top packaging, shrink wrapping, attached components (e.g., stapled, glued, etc.), or combinations thereof. A single package is a physically associated container of the individual dietary compositions of the present invention and can be considered as one unit for the purposes of manufacture, distribution, sale, or use. 【0020】

[0020] The term “virtual package” means that the components of the kit are associated with instructions for one or more physical or virtual kit components that explain to the user how to obtain other components, for example, a bag or other container that includes one component and instructions that tell the user to view a website, contact a recorded message or fax reply service, view a visual message, or contact a caregiver or instructor to obtain instructions on how to use the kit or safety or technical information regarding one or more components of the kit. 【0021】

[0021] The term "approximately" means plus or minus 20%, preferably plus or minus 10%, more preferably plus or minus 5%, and most preferably plus or minus 2%. 【0022】

[0022] All percentages expressed in this application refer to the total weight or total amount of the composition unless otherwise stated. 【0023】

[0023] The specific methodologies, protocols, and reagents described herein are modifiable and therefore the present invention is not limited thereto. Furthermore, the terms used herein are for the sole purpose of describing specific embodiments and are not intended to limit the scope of the present invention. 【0024】

[0024] Where used herein, unless explicitly stated by context, the singular form of a word is inclusive of the plural form, and vice versa. Thus, references to “a,” “an,” and “the” generally include the plural form of the respective term. Similarly, the words “comprise,” “comprises,” and “comprising” should be interpreted as inclusive of others, not exclusive. Likewise, the terms “include,” “including,” and “or” should all be interpreted as inclusive of others, unless such interpretation is clearly prohibited by context. Similarly, the term “examples,” especially when followed by a list of terms, is merely illustrative and explanatory and should not be considered exclusive or inclusive. All embodiments using “comprise,” “comprises,” or “comprising” may be replaced with “essentially consisting of” or “consisting of.” 【0025】

[0025] Unless otherwise stated, all technical and scientific terms and any abbreviations used herein have the same meaning as those generally understood by those skilled in the art to which the present invention pertains. Any composition, method, product, or other technique or material similar or equivalent to those described herein may be used in carrying out the present invention, but preferred compositions, methods, products, or other techniques or materials are described herein. 【0026】 All patents, patent applications, publications, and other references cited or referred to in this specification are hereby incorporated by reference into this specification to the extent permitted by law. The discussion of these references is intended only to summarize the claims made in those references. It is not to be understood that such patents, patent applications, publications, or references, or any portion thereof, are relevant prior art to the present invention, and the right to challenge the accuracy and appropriateness of such patents, patent applications, publications, and other references is expressly reserved. 【0027】 The present invention 【0027】In one embodiment, a method for treating, preventing, or delaying the onset of an organ disease or a decrease in organ function, or a condition related thereto in an animal, includes feeding the animal a maintenance diet containing calories sufficient to meet the animal's maintenance energy requirement during a maintenance calorie period, and feeding the animal a reduced-calorie diet containing about 40% to about 60% of the calories contained in the maintenance diet during a reduced-calorie period, and the ratio of the maintenance calorie period to the reduced-calorie period is about 4:3. 【0028】 【0028】In one embodiment, a method for treating, preventing, or delaying the onset of an organ disease or a decrease in organ function, or a condition related thereto in an animal, includes feeding the animal at discretion during a discretionary period, and feeding the animal a reduced-calorie diet containing about 40% to about 60% of the animal's maintenance energy requirement during a reduced-calorie period, and the ratio of the discretionary period to the reduced-calorie period is about 4:3. 【0029】 【0029】In another embodiment, a method for reducing the biological age in an adult animal or the biological age of an organ in an adult animal can include feeding an adult animal a maintenance diet containing calories that meet the maintenance energy requirement of the adult animal during a calorie maintenance period, and feeding the adult animal a calorie-restricted diet containing about 40% to about 60% of the calories contained in the maintenance diet during a calorie restriction period, and the ratio of the calorie maintenance period to the calorie restriction period is about 4:3. 【0030】 【0030】In another embodiment, a method for reducing the biological age in an adult animal or the biological age of an organ in an adult animal can include feeding the adult animal at will during a discretionary period, and feeding the adult animal a calorie-restricted diet containing about 40% to about 60% of the maintenance energy requirement of the animal during a calorie restriction period, and the ratio of the calorie maintenance period to the calorie restriction period is about 4:3. 【0031】 【0031】Notably, the inventors unexpectedly discovered that animals fed in a specific intermittent feeding pattern (a 4:3 period ratio) with a specific calorie reduction can reduce the biological age of the animal and can treat, prevent, or delay the onset of organ diseases, organ function decline, or conditions associated with organ diseases in the animal. For example, an animal can be fed a maintenance diet (or discretionary diet) for 4 days and a reduced diet for 3 days. Generally, the reduced diet contains about 40% to about 60% of the calories contained in the maintenance diet. In one aspect, the reduced diet can have about 50% of the calories. 【0032】

[0032] Accordingly, the treatment, prevention, or delay of organ diseases, impaired organ function, or related conditions by this method may include liver disease or liver function, heart disease or heart function, muscle disease or muscle function, brain disease or brain function, kidney disease or kidney function, gastrointestinal disease or gastrointestinal function, eye disease or eye function, lung disease or lung function, bone disease or bone function, skin disease or skin function, and immune disease or immune function. 【0033】

[0033] In one embodiment, the method can treat, prevent, or delay the onset of liver diseases or related conditions, including fatty liver, cirrhosis, age-related decrease in liver volume and blood flow, and / or hepatic fibrosis. 【0034】

[0034] In another embodiment, the method can treat, prevent, or delay the onset of heart disease or related conditions, including cardiac hypertrophy, cardiac hypertrophy, myocardial hypertrophy, ventricular hypertrophy, and / or hypertension. 【0035】

[0035] In another embodiment, the method can treat, prevent, or delay the onset of muscle diseases or related conditions, including skeletal muscle loss, loss of strength, sarcopenia, frailty, decreased or reduced mobility, and / or muscle atrophy. 【0036】

[0036] In another embodiment, the method can treat, prevent, or delay the onset of brain diseases or related conditions, including aging of the brain, memory loss or decline, learning ability loss or decline, executive function loss or decline, balance and motor coordination loss or decline, and / or sensory function loss or decline. 【0037】

[0037] In another embodiment, the method can treat, prevent, or delay the onset of kidney disease or related conditions, including chronic kidney disease, renal failure, decreased functional glomeruli due to increased prevalence of nephrosclerosis, arteriosclerosis, glomerulosclerosis, tubular atrophy with interstitial fibrosis, decreased cortical volume, renal cysts, decreased glomerular filtration rate, and / or decreased or impaired renal reserve. 【0038】

[0038] In another embodiment, the method can treat, prevent, or delay the onset of gastrointestinal diseases or related conditions, including gastric ulcers or inflammation, duodenal ulcers or inflammation, jejunal ulcers, irritable bowel disorder (IBD), constipation, hemorrhoids, colitis, colon polyps, gastroesophageal reflux disease (GERD), diarrhea, gastroenteritis, leaky gut syndrome, conditions associated with leaky gut syndrome (anxiety, depression, chronic diarrhea, constipation, or bloating, malnutrition, fatigue, headache, confusion, difficulty concentrating, skin problems (such as acne, rash, or eczema), arthralgia, inflammation), and / or bloating and excessive gas. 【0039】

[0039] In another embodiment, the method can treat, prevent, or delay the onset of eye diseases or related conditions, including cataracts, decreased or impaired retinal function, and / or amblyopia. 【0040】

[0040] In another embodiment, the method can treat, prevent, or delay the onset of lung diseases or related conditions, including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung infections, decreased or reduced lung reserve, decreased or reduced coughing ability, decreased or reduced lung muscle function, and / or decreased or reduced lung immune function. 【0041】

[0041] In another embodiment, the method can treat, prevent, or delay the onset of immune disorders or related conditions, including decreased or reduced immune function and / or immunosenescence and / or decreased or reduced vaccine response. 【0042】

[0042] In another embodiment, the method can treat, prevent, or delay the onset of bone diseases or related conditions, including bone density, bone strength, and / or osteoporosis. 【0043】

[0043] In another embodiment, the method can treat, prevent, or delay the onset of skin diseases or related conditions, including wrinkles, loss of elasticity, sagging, rough appearance, blemishes, lesions, and dry skin. 【0044】

[0044] While feeding during the calorie reduction and calorie maintenance periods as described may be sufficient, the method also includes embodiments in which the feeding pattern is repeated for at least two cycles, several cycles, as long as the animal benefits from the feeding pattern (e.g., treating or preventing liver disease), or for the lifetime of the animal. 【0045】

[0045] This method is intended for use over any time cycle, such as 5, 7, 10, or 14 days. Within a cycle, if the ratio of individual maintenance periods to restriction periods is 4:3, the calorie maintenance period may be approximately 4 days and the calorie reduction period may be approximately 3 days. Furthermore, individual feedings / days can be carried out in a discontinuous manner throughout the entire cycle (e.g., a weekly cycle with 2 days of maintenance followed by 2 days of restriction, then 2 days of maintenance, then 1 day of restriction), but generally, individual periods can be continuous (e.g., a weekly cycle with 4 days of maintenance followed by 3 days of restriction). Thus, in one embodiment, the 4 days and 3 days may be continuous, and in another embodiment, the 4 days and 3 days may be discontinuous. 【0046】

[0046] While feeding during calorie reduction periods and discretionary feeding periods as described may be sufficient, the method also includes embodiments in which the feeding pattern is repeated for at least two cycles, several cycles, as long as the animal benefits from the feeding pattern (e.g., treating or preventing liver disease), or for the lifetime of the animal. 【0047】

[0047] The method is intended for use over any time cycle, such as 5, 7, 10, or 14 days, but within a cycle, if the ratio of individual discretionary periods to restricted periods is 4:3, the discretionary period may be approximately 4 days and the calorie reduction period may be approximately 3 days. Furthermore, individual feedings / days may unfold discontinuously throughout the entire cycle (e.g., a weekly cycle with 2 days of discretion, then 2 days of restriction, then 2 days of discretion, then 1 day of restriction), but generally, individual periods may be continuous (e.g., a weekly cycle with 4 days of discretion, then 3 days of restriction). Thus, in one embodiment, the 4 days and 3 days may be continuous, and in another embodiment, the 4 days and 3 days may be discontinuous. 【0048】

[0048] As discussed herein, the intermittent feeding of the present invention may be for any duration and any number of cycles, and in one embodiment, the feeding of a calorie maintenance period and the feeding of a calorie reduction period are repeated over a combined period of at least one month. In one embodiment, the feeding of a calorie maintenance period and the feeding of a calorie reduction period may be repeated over a period of at least six months. In another embodiment, the feeding of a calorie maintenance period and the feeding of a calorie reduction period may be repeated over a period of at least one year, two years, five years, ten years, or even over the remainder of the animal's life. 【0049】

[0049] As discussed herein, the intermittent feeding of the present invention may be of any duration and any number of cycles, and in one embodiment, the feeding of discretionary periods and the feeding of calorie reduction periods are repeated over a combined period of at least one month. In one embodiment, the feeding of discretionary periods and the feeding of calorie reduction periods may be repeated over a period of at least six months. In other embodiments, the feeding of discretionary periods and the feeding of calorie reduction periods may be repeated over a period of at least one year, two years, five years, ten years, or even over the remainder of the animal's life. 【0050】

[0050] In one embodiment, the method of the present invention is carried out in conjunction with the administration of a therapeutic agent or any other active substance that provides a health benefit. Any such active substance that fits the feeding pattern of the present invention can be used in the present invention. In various embodiments, the active ingredients may be carnitine, isoflavones, pirubate, fish oil, ω-3 polyunsaturated fatty acids, ω-6 polyunsaturated fatty acids, monounsaturated fatty acids (ω-7 and ω-9 fatty acids), fiber, calcium, indigestible starch, medium-chain triglycerides, green tea leaf extract, phentermine, diethylpropion, orlistat, sibutramine, megestrol, resveratrol, plant polyphenols, phenylpropanolamine, acarbose, amylase and / or α-glucosidase inhibitors such as Phase 2 (white bean extract) and Reduce® (mulberry leaf extract), lipase inhibitors such as orlistat, oxandrolone, and oleoylethanolamide, probiotics, ephedra, conjugated linoleic acid, glucomannan, and mixtures thereof. 【0051】

[0051] The methods described herein may be useful for reducing the biological age of an animal or an organ of an animal, and for treating, preventing, or delaying the onset of any organ disease or organ dysfunction or related condition in any animal. In one embodiment, such methods may be applied to companion animals, including those whose diet is controlled by an owner or caretaker. In one particular embodiment, the animal may be a dog and / or a cat. In one embodiment, the animal may be an adult animal. In another embodiment, the animal may be an elderly animal. In yet another embodiment, the animal may be an aged animal. 【0052】

[0052] In a further embodiment, the present invention provides a kit suitable for carrying out the method of the present invention. The kit includes, in a separate container in a single package or in a separate container in a virtual package as appropriate to the kit components, (1) a complete and balanced first food composition containing calories to meet the maintenance energy requirements of an animal; (2) a complete and balanced second food composition containing calories not to meet the maintenance energy requirements of an animal; and (3) instructions for using the food composition for at least one of reducing the biological age of an animal or an organ of an animal, or treating, preventing or delaying the onset of an organ disease or organ dysfunction or a related condition by feeding the animal the first food composition during a first period and the second food composition during a second period. In certain embodiments, the kit further includes one or more health-enhancing or therapeutic agents. 【0053】

[0053] If the kit includes a virtual package, the kit is limited to instructions in a virtual environment combined with one or more physical kit components. Generally, the kit contains a sufficient amount of food composition and other physical components to carry out the method of the present invention, and the virtual package includes instructions relating to carrying out the method of the present invention using the physical components. 【0054】

[0054] In another embodiment, the present invention provides means for communicating information or instructions for treating, preventing, or delaying the onset of organ disease or organ dysfunction or related conditions by reducing the biological age of an animal or an organ, or by feeding an animal a calorie-maintaining diet containing calories that meet the animal's maintenance energy requirements during a calorie-maintaining period, or by feeding an animal a calorie-reducing diet containing calories that do not meet the animal's maintenance energy requirements during a calorie-reducing period, or optionally by administering therapeutic agents or other health-enhancing agents. The means include documents, digital recording media, optical recording media, audio presentations, or visual displays containing information or instructions. In particular embodiments, the means of communication are displayed websites, visual displays, brochures, product labels, accompanying documents, advertisements, handouts, notices, audio tapes, video tapes, DVDs, CD-ROMs, computer-readable chips, computer-readable cards, computer-readable disks, computer memory, or combinations thereof containing such information or instructions. 【0055】

[0055] Useful information may include one or more of the following: (1) recommended feeding plans for animals based in particular on the animal species and physical condition (e.g., liver disease); (2) therapeutic agents or health supplements recommended for administration in conjunction with the use of the recommended feeding patterns; and (3) contact information for the animals or their owners for use in case of any questions regarding the present invention and its use. 【0056】 [Examples]

[0056] The present invention can be further illustrated by the following embodiments, but these embodiments are given for illustrative purposes only and should be understood not to limit the scope of the present invention unless otherwise stated. 【0057】 Example 1 - Rat Organ Test

[0057] Male rats were fed a high-fat diet (HFD, 45% fat) for 14 weeks after weaning to induce overweight. After this weight-gaining diet period, the rats were randomized to the following groups, each containing 12 rats for 6 months: Control group: Rats fed the AIN-93M diet (control) continued to receive 100% MER daily for 6 months. Long-term restriction (CR) group: Rats were fed a 25% diet daily, 25% less than MER, due to reduced dietary carbohydrate intake. Intermittent calorie restriction (ICR) group: Rats were fed a 50% diet three days a week, 50% less than MER, due to reduced dietary carbohydrate intake, and the remaining four days a week were fed the 100% MER control diet. The diet composition is shown in Table 1. 【0058】 [Table 1] 【0059】

[0058] During the 6-month feeding trial, rats in all test groups ingested the same amounts of protein, fat, vitamins, and minerals as rats in the control group. The reduction in calories was solely due to the reduction in carbohydrate intake from the special diet shown in Table 1. 【0060】

[0059] At the end of the study, when tissue samples were collected, the rats were approximately 11 months old. Liver samples were collected and subjected to an epigenetic biological clock assay to determine the biological age of the livers of the groups provided in Table 2. 【0061】 [Table 2] 【0062】

[0060] The results showed that the biological age and chronological age of the livers of control rats were identical. The previously reported 25% CR as an anti-aging intervention reduced the biological age of rat livers by 15.53%. Surprisingly, the ICR regimen, despite having less calorie restriction (21.4%) compared to CR (25%), had the strongest effect on the biological age of rat livers, reducing it by 23.04%. To reiterate, rats on the ICR regimen of the present invention had younger livers than rats on the CR diet, even when consuming more calories, which was completely unexpected. 【0063】

[0061] It should be understood that various changes and modifications to the current preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the spirit and scope of the subject matter and without impairing the intended advantages. Accordingly, such changes and modifications are intended to be covered by the appended claims.

Claims

[Claim 1] A method for treating, preventing, or delaying the onset of age-related decreases in liver volume and hepatic blood flow in non-human animals, During the calorie maintenance period, the non-human animals are fed a calorie-maintaining diet containing calories that meet the energy requirements of the non-human animals. This includes feeding the non-human animal a calorie-reduced diet containing approximately 40% to 60% of the calories contained in the calorie-maintaining diet during the calorie reduction period, The aforementioned calorie-reduced diet is a diet in which the amount of carbohydrates is reduced from the aforementioned calorie-maintaining diet. The ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. A method comprising repeating at least two cycles of 7 days or 14 days, wherein the ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. [Claim 2] The method according to claim 1, wherein the duration of the cycle is 7 days, the calorie maintenance period is 4 days, and the calorie reduction period is 3 days. [Claim 3] The method according to claim 2, wherein the four days and the three days are consecutive. [Claim 4] The method according to claim 2, wherein the four days and the three days are discontinuous. [Claim 5] The method according to any one of claims 1 to 4, wherein the feeding during the calorie maintenance period and the feeding during the calorie reduction period are repeated for a period of at least one month. [Claim 6] The method according to any one of claims 1 to 4, wherein the feeding during the calorie maintenance period and the feeding during the calorie reduction period are repeated for a period of at least six months. [Claim 7] The method according to any one of claims 1 to 6, wherein the calorie-reduced diet contains about 50% of the calories necessary to meet the daily energy maintenance requirements of the non-human animal. [Claim 8] A kit comprising a calorie-maintaining diet and a calorie-reducing diet for use in a method for treating, preventing, or delaying the onset of age-related decrease in liver volume and hepatic blood flow in animals, wherein the method is During the calorie maintenance period, the animal is fed a calorie-maintaining diet containing calories that meet the animal's maintenance energy requirements. This includes feeding the animal a calorie-reduced diet containing approximately 40% to 60% of the calories contained in the calorie-maintaining diet during the calorie-reducing period, The aforementioned calorie-reduced diet is a diet in which the amount of carbohydrates is reduced from the aforementioned calorie-maintaining diet. The ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. A kit comprising a method of repeating at least two cycles of 7 or 14 days, in which the ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. [Claim 9] A method for reducing the biological age of the liver in non-human adult animals, During the calorie maintenance period, the non-human adult animals are fed a calorie maintenance diet containing calories that meet their required energy needs. This includes feeding the non-human adult animals a calorie-reduced diet containing approximately 40% to 60% of the calories contained in the calorie-maintaining diet during the calorie reduction period, The aforementioned calorie-reduced diet is a diet in which the amount of carbohydrates is reduced from the aforementioned calorie-maintaining diet. The ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. A method comprising repeating at least two cycles of 7 days or 14 days, wherein the ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. [Claim 10] The method according to claim 9, wherein the duration of the cycle is 7 days, the calorie maintenance period is 4 days, and the calorie reduction period is 3 days. [Claim 11] The method according to claim 9 or 10, wherein the calorie maintenance period and the calorie reduction period are continuous in the cycle. [Claim 12] The method according to any one of claims 9 to 11, wherein the feeding during the calorie maintenance period and the feeding during the calorie reduction period are repeated for a period of at least one month. [Claim 13] The method according to any one of claims 9 to 11, wherein the feeding during the calorie maintenance period and the feeding during the calorie reduction period are repeated for a period of at least six months. [Claim 14] The method according to any one of claims 9 to 13, wherein the calorie-reduced diet contains about 50% of the calories necessary to meet the daily energy maintenance requirements of the non-human adult animal. [Claim 15] The method according to any one of claims 9 to 14, wherein the non-human adult animal is an elderly animal. [Claim 16] A kit comprising a calorie-maintaining diet and a calorie-reducing diet for use in a method for reducing the biological age of the liver in adult animals, wherein the method is During the calorie maintenance period, the adult animals are fed a calorie-maintaining diet containing calories that meet their required energy needs. This includes feeding the adult animals a calorie-reduced diet containing approximately 40% to 60% of the calories contained in the calorie-maintaining diet during the calorie-reducing period, The aforementioned calorie-reduced diet is a diet in which the amount of carbohydrates is reduced from the aforementioned calorie-maintaining diet. The ratio of the calorie maintenance period to the calorie reduction period is approximately 4:

3. A kit comprising a method of repeating at least two cycles of 7 or 14 days, in which the ratio of the calorie maintenance period to the calorie reduction period is approximately 4:3.

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