Metformin, aging and cancer
Abstract
Many cancers are associated with aging [1]. Metformin, a widely used antidiabetic drug, has been linked to a reduced cancer incidence in some retrospective, hypothesis-generating studies [2]. Since cancer and aging may share certain molecular processes, it is plausible that metformin may prevent cancer by acting on the aging process. Consistent with this idea, several studies report a life span extension in animal models after treatment with metformin [3].
What is the mechanism by which aging may increase cancer incidence? Although many molecular changes correlate with aging, the presence of senescent cells capable of secreting inflammatory cytokines may be involved. This senescence associated secretory phenotype (SASP) consists of multiple cytokines, chemokines, growth factors and extracellular matrix degrading enzymes that can potentially affect normal tissue structure [4]. The SASP probably evolved as a gene expression program to assist the senescent tumor suppression response and tissue repair after damage and should be viewed as an initial adaptive response [5]. However, like acute inflammation, the SASP should be turned off to avoid maladaptive consequences. In some contexts, senescent cells are cleared by professional phagocytic cells [6] and this mechanism avoids any further complications. On the other hand, if senescent cells escape clearance, mechanisms that prevent the SASP should operate to avoid chronic inflammation and tissue disruption. Such endogenous…
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