Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in drosophila

Slack, Cathy, Foley, Andrea and Partridge, Linda (2012). Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in drosophila. PLoS ONE, 7 (10),

Abstract

The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1. We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster. We show here that while feeding metformin to adult Drosophila resulted in a robust activation of AMPK and reduced lipid stores, it did not increase lifespan in either male or female flies. In fact, we found that when administered at high concentrations, metformin is toxic to flies. Furthermore, no decreases in female fecundity were observed except at the most toxic dose. Analysis of intestinal physiology after metformin treatment suggests that these deleterious effects may result from disruptions to intestinal fluid homeostasis. Thus, metformin appears to have evolutionarily conserved effects on metabolism but not on fecundity or lifespan.

Publication DOI: https://doi.org/10.1371/journal.pone.0047699
Divisions: Life & Health Sciences
Additional Information: © Slack 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.
Uncontrolled Keywords: Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
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Related URLs: http://www.scopus.com/inward/record.url?scp=84867621125&partnerID=8YFLogxK (Scopus URL)
Published Date: 2012-10-16
Authors: Slack, Cathy ( 0000-0002-7949-4079)
Foley, Andrea
Partridge, Linda

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