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Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila
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Roman, Gregg, 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). e47699. doi:10.1371/journal.pone.0047699 ISSN 1932-6203.
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Official URL: http://doi.org/10.1371/journal.pone.0047699
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.
Item Type: | Journal Article | ||||||
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Subjects: | Q Science > QL Zoology Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Library of Congress Subject Headings (LCSH): | Drosophila melanogaster, Protein kinases, Metformin , Longevity, Longevity -- Nutritional aspects | ||||||
Journal or Publication Title: | PLoS One | ||||||
Publisher: | Public Library of Science | ||||||
ISSN: | 1932-6203 | ||||||
Official Date: | 16 October 2012 | ||||||
Dates: |
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Volume: | 7 | ||||||
Number: | 10 | ||||||
Article Number: | e47699 | ||||||
DOI: | 10.1371/journal.pone.0047699 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 18 May 2023 | ||||||
Date of first compliant Open Access: | 18 May 2023 | ||||||
RIOXX Funder/Project Grant: |
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