CN-122003237-A - Method for increasing longevity in mammals

Abstract

Provided herein are methods of reducing or reversing aging-induced insulin resistance and/or fatty acid elevation comprising a composition comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof. Provided herein are methods of extending longevity comprising a composition comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof, and the use of the composition in animal health.

Inventors

• Celine Leah Haliua Humboldt
• Michael. Lacroix Fraleish
• Matt Pelosi Kun
• Tina Juarez Salinas
• Karen Greenwood

Assignees

• 乐佑动物健康公司

Dates

Publication Date

20260508

Application Date

20240327

Priority Date

20230327

Claims (20)

1. 1. A method for reducing or reversing aging-induced insulin resistance in a mammal in need thereof, the method comprising administering to a companion animal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof.
2. 2. A method for reducing or reversing insulin resistance in a mammal in need thereof, the method comprising administering to a companion animal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof.
3. 3. A method for reducing or reversing aging-induced elevated circulating lipids, including fatty acids, triglycerides or cholesterol, in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof.
4. 4. A method of maintaining or restoring healthy function to adipose tissue in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof.
5. 5. The method of any one of claims 1-4, wherein the method does not reduce the glucose level of the companion animal.
6. 6. The method of any one of claims 1-5, wherein the method does not increase the glucose level of the companion animal.
7. 7. The method of any one of claims 1-6, wherein the method comprises reducing insulin levels in the companion animal.
8. 8. The method of claim 7, wherein the decrease in insulin level is at least 5% decrease.
9. 9. The method of claim 8, wherein the reduction in insulin levels is at least 10%, at least 15%, or at least 20%.
10. 10. The method of any one of claims 1 to 9, wherein the method improves insulin sensitivity.
11. 11. The method of claim 10, wherein the insulin sensitivity is measured by an oral glucose tolerance test assay.
12. 12. The method of claim 10, wherein the insulin sensitivity is measured by a hyperinsulinemic positive glucose clamp test assay.
13. 13. The method of claim 10, wherein the insulin sensitivity is measured by using fasting insulin blood levels.
14. 14. The method of any one of claims 3 or 5 to 13, wherein the lipid is aggregated free fatty acids, saturated fatty acids, palmitic acid, linoleic acid, or oleic acid, or any combination thereof.
15. 15. The method of claim 14, wherein the fatty acid is a saturated fatty acid.
16. 16. The method of claim 14, wherein the fatty acid is palmitic acid.
17. 17. The method of any one of claims 1 to 16, wherein the method reduces triglyceride levels in the mammal.
18. 18. The method of any one of claims 1 to 17, wherein the method increases adiponectin levels in the mammal.
19. 19. The method of any one of claims 1 to 17, wherein the method reduces cholesterol levels in the mammal.
20. 20. The method of any one of claims 1 to 19, wherein the mammal is a dog or cat.

Description

Method for increasing longevity in mammals Cross Reference to Related Applications The present application claims the benefit of U.S. provisional application No. 63/454,874, filed on 3/27 of 2023, which is incorporated herein by reference in its entirety. Background It is well known that chronological age is the largest risk factor for almost every major cause of death and morbidity of organisms, including humans and companion dogs. Even before the observable disease progresses, the physiology of organ systems and tissues gradually decline throughout life. Throughout the history, products and methods that promote longevity and extend life have been eagerly sought. In general, these products and methods have proven to be ineffective and/or unsafe. Thus, there remains an unmet need for safe and effective products and methods that promote longevity and extend life. Disclosure of Invention In some embodiments, provided herein is a method for reducing or reversing aging-induced insulin resistance in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, provided herein is a method for reducing or reversing insulin resistance in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, provided herein is a method for reducing or reversing aging-induced fatty acid and other lipid elevations in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, provided herein is a method of maintaining healthy function of adipose tissue in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a formulation comprising a pparγ agonist or a pharmaceutically acceptable salt or prodrug thereof. In some embodiments, the method does not reduce the glucose level of the mammal. In some embodiments, the method does not increase the glucose level of the mammal. In some embodiments, the method comprises reducing insulin levels in the mammal. In some embodiments, the decreasing insulin level is at least 5% decrease. In some embodiments, the decreasing insulin level is at least 10%, at least 15%, or at least 20%. In some embodiments, the method improves insulin sensitivity. In some embodiments, the insulin sensitivity is measured by an oral glucose tolerance test assay. In some embodiments, the insulin sensitivity is measured by using fasting insulin blood levels. In some embodiments, the insulin sensitivity is measured by a hyperinsulinemic positive glucose clamp test assay. In some embodiments, the lipid is aggregated free fatty acids, saturated fatty acids, palmitic acid, linoleic acid, or oleic acid, or any combination thereof. In some embodiments, the fatty acid is a saturated fatty acid, palmitic acid, linoleic acid, or oleic acid. In some embodiments, the fatty acid is a saturated fatty acid. In some embodiments, the fatty acid is palmitic acid. In some embodiments, the method reduces triglyceride levels in the mammal. In some embodiments, the method reduces cholesterol levels in the mammal. In some embodiments, the method increases adiponectin levels in the mammal. In some embodiments, the mammal is a dog, cat, horse, cow, pig, rabbit, rodent, sheep, non-human primate, or human. In some embodiments, the mammal is a dog or cat. In some embodiments, the mammal is a dog. In some embodiments, the mammal is a cat. In some embodiments, the rodent is a mouse or a rat. In some embodiments, the mammal is a human. In some embodiments, the mammal is at least 7 years old. In some embodiments, the mammal is at least 10 years old. In some embodiments, wherein the formulation comprises from about 3% to about 35% of the pparγ agonist. In some embodiments, wherein the formulation comprises from about 10% to about 20% of the pparγ agonist. In some embodiments, wherein the formulation comprises from about 1 mg to about 100 mg of the pparγ agonist. In some embodiments, the formulation comprises from about 4 mg to about 85 mg of the pparγ agonist. In some embodiments, the pparγ agonist is administered at 3 mg/kg/day. In some embodiments, the pparγ agonist is administered at 5 mg/kg/day. In some embodiments, the pparγ agonist is administered at 10 mg/kg/day. In some embodiments, the formulation is administered for at least about 4 weeks. In some embodiments, the formulation is administered for at least about 12 weeks. In some embodiments, the formulation is administered for at least about 6 months. The formulation is administered for at least about 1 year. In some embodim