activation and inhibition are proposed as anti-aging-oriented therapeutic targets for type 2 diabetes and its complications.
Evidence
This review synthesizes mechanistic and intervention evidence linking type 2 diabetes, aging hallmarks, AMPK, mTORC1, nutritional interventions, antidiabetic drugs, and senolytics.
Caveat
The abstract presents a mechanistic rationale rather than direct clinical trial evidence that these strategies slow aging in people with type 2 diabetes.
Simplified
Aging is a complicated biological process that induces a decline in the human organs' structure and function and elevates the risks of aging-related diseases such as Alzheimer's disease (AD) and type 2 diabetes. Type 2 diabetes accelerates all clinical manifestations of aging. Metabolic disorders in type 2 diabetes are unfavorably associated with all hallmarks of aging, such as inflammation and mitochondrial dysfunction. Adenosine monophosphate-activated protein kinase () and the mammalian target of rapamycin complex 1 () are key players in cellular metabolism, and AMPK activation and mTORC1 inhibition improve all hallmarks of aging. AMPK activation and mTORC1 inhibition are favorably associated with diabetic complications. Nutritional interventions, such as caloric restriction, resveratrol, and astaxanthin, have AMPK-activating and mTORC1-inhibitory effects and improve metabolic abnormalities in type 2 diabetes. Anti-diabetic drugs, metformin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide 1 receptor agonists have been reported to have AMPK-activating and mTORC1-inhibiting effects and show prevention of aging-related diseases such as cardiovascular disease. The therapeutic interventions that activate AMPK and inhibit mTORC1 may be optimal treatments for type 2 diabetes from the perspective of anti-aging medicine. Furthermore, senolytics may be a promising, direct anti-aging therapeutic strategy specifically for type 2 diabetes and its complications.
Key numbers
-6.33 kg
Caloric Restriction Weight Loss
Mean difference in body weight after 6 months of caloric restriction.
-13.34 mg/dL
Resveratrol Fasting Blood Glucose Improvement
Mean difference in fasting blood glucose from a meta-analysis of 17 RCTs.
14%
SGLT2 Inhibitors 3-Point MACE Reduction
Reduction in incidence of 3-point MACE compared to placebo.
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