Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease

Abstract

Aging is a major global challenge, and there is growing demand for new strategies to address the burden of aging. The intensive search for antiaging agents has led to the discovery of a variety of drugs that promote the extension of healthspan and/or life. Metformin is a safe, effective, and globally affordable antihyperglycemic agent that has gained much attention in recent years as a potential antiaging treatment. Metformin has been shown to significantly delay the onset of age-related diseases and increase lifespan in several model organisms. In this paper, we reviewed aging hallmarks and the role of metformin in countering these hallmarks. We examined the beneficial effects of metformin on several age-related diseases and the feasibility of metformin as an agent to extend lifespan and healthspan. Finally, we discussed new research directions to better understand the translational potential of metformin in humans.

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

“…Acarbose is an inhibitor of alpha-glucosidases, a class of intestinal enzymes necessary to digest carbohydrates [27]. Acarbose exerts anti-inflammatory effects on human monocytic THP-1 cells [28], and Sadagurski et al [29] suggested that acarbose may prolong lifespan in mice by inhibiting age-related hypothalamic inflammation. Metformin appears to exert antiaging actions via multiple mechanisms, including nutrient sensing, DNA repair, oxidative stress, telomere attrition, inflammation, cellular senescence, stem cell decline, and autophagy [30].…”

Modulation of tumor plasticity by senescent cells: Deciphering basic mechanisms and survival pathways to unravel therapeutic options

“…Its inhibitors (e.g. metformin) could sensitize SnCs while also acting as senomorphics, another class of senotherapeutics capable of altering the composition of the SASP through the modulation of intracellular pathways ( Cheng et al, 2022 ). Molecules with senomorphic properties have become increasingly relevant since signaling mediated by some proteins encoded by oncogenes can also modulate the production of SASP.…”

Insights into the Role of Histone Methylation in Brain Aging and Potential Therapeutic Interventions

“…The neuroprotective effects of metformin have been associated with its ability to induce autophagy [72]. This mechanism involves the activation of 5 AMP-activated protein kinase (AMPK) and the suppression of mTOR signaling, leading to enhanced autophagic processes and facilitating the lysosomal degradation of Aβ [73]. As a result, metformin significantly reduces Aβ levels in the brain.…”