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

Cathy Slack, Andrea Foley, Linda Partridge

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere47699
Number of pages7
JournalPLoS ONE
Volume7
Issue number10
DOIs
Publication statusPublished - 16 Oct 2012

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metformin
AMP-activated protein kinase
dietary restriction
AMP-Activated Protein Kinases
Metformin
Drosophila
Chemical activation
Diptera
Fertility
fecundity
Poisons
biguanides
Biguanides
Physiology
Medical problems
fruit flies
Fruits
Drosophila melanogaster
noninsulin-dependent diabetes mellitus
Metabolism

Bibliographical note

© 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.

Cite this

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Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in drosophila. / Slack, Cathy; Foley, Andrea; Partridge, Linda.

In: PLoS ONE, Vol. 7, No. 10, e47699, 16.10.2012.

Research output: Contribution to journalArticle

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