Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals.
Insulin-like signalling is a key determinate of lifespan in diverse species including mammals but the mechanism by which this pathway influences the rate of aging is unknown. In the roundworm Caenorhabditis elegans, mutations in the insulin-like signalling pathway extend adult lifespan and are associated with up-regulation of stress response genes including those for heat shock proteins (HSPs). We tested the hypothesis that the C. elegans insulin-like signalling pathway determines longevity through modulating HSP levels. We introduced extra copies of the gene encoding HSP-16 and this conferred stress resistance and longevity both in a wildtype and a long-lived mutant strain. The DAF-16 transcription factor is essential for maximal hsp-16 expression and for lifespan extension conferred by hsp-16. This demonstrates that lifespan is determined in part by insulin-like regulation of molecular chaperones.
Walker
Glenda A
GA
The Buck Institute, 8001 Redwood Blvd., Novato, CA 94945, USA.
Lithgow
Gordon J
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature; D007328:Insulin; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D007328:Insulin; D018832:Molecular Chaperones; D014157:Transcription Factors; C108831:daf-16 protein, C elegans