Aging versus long life: the molecules involved

Investigators have found that the transcription factor DAF-16 controls the expression of a battery of genes, many of which have small effects on lifespan (promoting either ageing or longevity) in Caenorhabditis elegans. Consistent with earlier studies, the pro-longevity genes include some that encode antioxidant enzymes and others that encode heat-shock proteins,which can restore misfolded proteins to their active conformations. Genes that promote ageing include some that encode yolk proteins, consistent with a link between ageing and reproduction. Another pro-ageing protein is the insulin-like INS-7, which, by binding to the insulin/IGF-1 receptor (DAF-2), may repress DAF-16 on the same and other cells. This suggests the presence of a positive feedback loop that regulates DAF-2 activity. Arrows indicate activation; T-bars indicate inhibition.