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Diabetes mellitus (DM) is a cause of accelerated aging that shares mechanisms with physiological aging. The increased prevalence of DM is partially due to the expansion of the elderly population. Hypoglycemia and cardiovascular disease (CVD) are more common in older patients with diabetes. Aging mainly affects beta-cell secretory function. Insulin sensitivity also decreases with age, likely related to the genetic background, deleterious lifestyle changes, and comorbidities. In patients with DM, organ and system dysfunction occurs at younger ages, especially if DM is poorly controlled. Macrovascular and microvascular alterations are the most relevant and premature manifestations of aging in DM; they also exert a significant impact on the aging process and act as determinants of the human lifespan. Oxidative stress, endothelial dysfunction, and vascular inflammation underlie the pathogenesis of vascular complications. Patients with DM are also prone to develop age-related comorbidities such as frailty, cognitive impairment, Alzheimer’s disease, bladder dysfunction, osteoporosis, visual impairment, and kidney failure, among others, indicating that DM represents a proaging state. Potential mechanisms of premature aging in DM are likely linked to hyperglycemia, which, via the accelerated accumulation of advanced glycation end products into tissues and organs, enhances the production of proinflammatory factors and stimulates oxidative stress. Telomere shortening along with senescence of the cells, tissues, and organs are the end results. Reducing the senescent cell burden and their senescence-associated secretory phenotype (SASP) might be a novel therapeutic strategy for DM and its complications. Metformin exerts effects on diverse molecular aging pathways, modulates oxidative stress, and eliminates senescent cells by unclear mechanisms. To assess whether metformin may delay the onset of age-related conditions such as cancer, CV disease, and Alzheimer’s disease, the TAME trial is now being carried out in older adults. |
