Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila.
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.
Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, London, United Kingdom.
Cathy
C
Slack
Andrea
A
Foley
Linda
L
Partridge
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004032:Diet; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008136:Longevity / Q000187:drug effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D010766:Phosphorylation
D029721:Drosophila Proteins; D008687:Metformin; C523914:AMPKalpha protein, Drosophila; D055372:AMP-Activated Protein Kinases