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Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.
Pubmed ID: 32990681 RIS Download
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NIA''s ITP is a multi-institutional study investigating treatments with the potential to exte nd lifespan and delay disease and dysfunction in mice. Priority consideration will be given to the treatments that are easily obtainable, reasonably priced, and can be delivered in the diet (preferred) or water. Interventions that require labor intensive forms of administration, such as daily injections or gavage, are not feasible within the design of the ITP. Treatments currently under study include: - Pharmaceuticals - Nutraceuticals - Foods - Diets - Dietary supplements - Plant extracts - Hormones - Peptides - Amino acids - Chelators - Redox agents - Other agents or mixtures of agents Although the mice involved in this study will be housed at the University of Michigan, the Jackson Laboratories, and the University of Texas Health Sciences Center at San Antonio, the project is designed to involve collaborations with investigators at any university, institute, or other organization that has ideas about pharmacological interventions that might decelerate aging and wishes to test these in a lifespan study of mice. Sponsors: This program is supported by the National Institute of Aging.
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