Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling

The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematodeCaenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor genedaf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. InC. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enablesC. elegans to endure harsh environments through morphological adaptation, improved cellular repair, and slowed metabolism. Considerable progress has been made uncovering mechanisms that are affected byC. elegans rIIS. However, from the beginning it has remained unclear to what extent rIIS extendsC. elegans lifespan by mobilizing dauer-associated mechanisms in adults. As we discuss, recent work has shed light on this question by determining that rIIS can extendC. elegans lifespan comparably through downstream processes that are either dauer-related or -independent. Importantly, these two lifespan extension programs can be distinguished genetically. It will now be critical to tease apart these programs, because each may involve different longevity-promoting mechanisms that may be relevant to higher organisms. A recent analysis of organismal “healthspan” has questioned the value ofC. elegans rIIS as a paradigm for understanding healthy aging, as op...

Source: Gerontology - October 25, 2017 Category: Geriatrics Source Type: research