Improvements in health, not survival, by late-onset metformin treatment. Mus musculus

The biguanide metformin improves health and survival in male mice; however, it is unclear whether metformin will confer health and lifespan benefits to mice when started late in life. Two year-old mice fed on standard chow were treated with 1% metformin every-other week (EOW) or two consecutive weeks per month (2WM). EOW mice displayed improvements in healthspan reminiscent of mice on caloric restriction. The age-associated histopathological changes in liver and kidney were significantly reduced in EOW compared to 2WM or control mice. Some of the affected gene transcripts and metabolites were found to be risk predictors of metabolic disorder. Neither EOW nor 2WM mice exhibited extension in mean or maximum lifespan compared with control animals. Thus, metformin supplementation had a strong impact on reversing some of the deleterious effects of aging and resulted in an improvement of health in old male mice in the absence of an extension of lifespan. Overall design: Two-year old mice were fed a standard diet (SD, n=4 biological replicates for microarray), SD+1% metformin, either every other week (EOW, n=5 biological replicates for microarray) or two consecutive weeks per month (2WM, n=4 biological replicates for microarray) for 17 weeks.