Effect of Metformin on the Lifespan and Health Span of Drosophila

Abstract

Metformin has been the most used drug to treat diabetes for nearly 70 years. It reduces the pressure on the mitochondria from over calorific foods (i.e., fast foods), which termed the Western Diet. Metformin’s ability to mildly decrease the efficiency of mitochondrial energy transformation has led to speculation that metformin may also promote healthy aging and extend longevity in non-diabetic, otherwise healthy individuals. Using the Drosophila model, we hypothesized that metformin, by decreasing mitochondrial and whole body bioenergetic efficiency, will increase lifespan in flies on the Western Diet but either decrease or have no effect in flies on a standard low-fat diet. Initial studies determined that in flight muscle mitochondria, titration of metformin (1-200 mM) or methyl-triphenylphosphonium (cation; mTPP; 0.01-0.25 mM) in vitro experiments induced a dose-dependent decrease in ADPstimulated oxygen consumption rate (JO2; normalized to complex IV activity). For in vivo studies, flies were fasted for 20 hours and then provided food containing mTPP (0-1.0 mM) with blue dye for two or four hours. Surprisingly, despite evidence of food consumption, no differences in ADP-stimulated JO2 were detected, suggesting either the flies did not consume enough food or that mTPP was not absorbed or ineffective in vivo. Results from Western Diet Studies showed no change in mitochondrial efficiencies for D. melanogaster however, for D. simulans, there was a lower mitochondrial efficiency in flies on the Western Diet that also exercised.