Metformin and sex: why suppression of aging may be harmful to young male mice
Year: 2010
Type: article
Abstract: © Blagosklonny et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Intriguingly, in this issue of Aging, Anisimov et al. reported that lifelong treatment with metformin (an antidiabetic drug with potentially anti-aging effects) was beneficial for female mice but shortened lifespan in males. Here I discuss why suppression of aging may be unfavorable in young males. Metformin is used for treatment of type II (adult-onset) diabetes. Also, metformin and its analog phenformin prevent cancer and increase lifespan in rodents [1-7]. Yet, effects of metformin depend on mice strains and gender. In one strain (transgenic female HER-2/neu mice), metformin slowed down aging and tumor development [3]. In another strain (female SHR mice), metformin slowed down aging without inhibiting spontaneous tumorigenesis [4]. In third strain (female 129/Sv mice), metformin decreased carcinogenesis but only marginally increased life span [8]. Unexpectedly, in male mice of the same 129/Sv strain, metformin decreased the mean life span by 13 % [8]. How can this be explained? There are 3 additional pieces to the puzzle. First, metformin via several mechanisms inhibits the mTOR pathway [9-15]. Second, inhibition of mTOR may explain the anti-aging effect of metformin [16,17]. Third, death rate was increased specifically in young males, thus decreasing their mean life span. Still, metformin did not affect lifespan of the last 10 % of survivors and maximum life span [8]. Death from “anti-aging” Growth and aging share a common molecular mechanism
Source: Aging
Author: Mikhail V. Blagosklonny
Institution: Roswell Park Comprehensive Cancer Center
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1567556960