Metformin: Sentinel of the Epigenetic Landscapes That Underlie Cell Fate and Identity.

ABSTRACT: The biguanide metformin is the first drug to be tested as a gerotherapeutic in the clinical trial TAME (Targeting Aging with Metformin). The current consensus is that metformin exerts indirect pleiotropy on core metabolic hallmarks of aging, such as the insulin/insulin-like growth factor 1 and AMP-activated protein kinase/mammalian Target Of Rapamycin signaling pathways, downstream of its primary inhibitory effect on mitochondrial respiratory complex I. Alternatively, but not mutually exclusive, metformin can exert regulatory effects on components of the biologic machinery of aging itself such as chromatin-modifying enzymes. An integrative metabolo-epigenetic outlook supports a new model whereby metformin operates as a guardian of cell identity, capable of retarding cellular aging by preve

SUBMITTER: Menendez JA 

PROVIDER: S-EPMC7277648 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature