The temporal scaling of Caenorhabditis elegans ageing

A diverse range of molecular and genetic manipulations all alter lifespan distributions of Caenorhabditis elegans by an apparent stretching or shrinking of time. The secret of ageing is timing This study in the nematode Caenorhabditis elegans , well established as a model organism in ageing research, shows that a range of different interventions — mutations in the insulin/IGF-1 signalling pathway, changes in ambient temperature, and chemically induced oxidative stress — all yield lifespan distributions that can be collapsed into a universal curve simply by rescaling the time axis. This phenomenon of 'temporal scaling' identifies a novel state variable, r ( t ), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of aging, kr . Interventions that produce temporal scaling influence lifespan exclusively by altering kr . The process of ageing makes death increasingly likely, involving a random aspect that produces a wide distribution of lifespan even in homogeneous populations 1 , 2 . The study of this stochastic behaviour may link molecular mechanisms to the ageing process that determines lifespan. Here, by collecting high-precision mortality statistics from large populations, we observe that interventions as diverse as changes in diet, temperature, exposure to oxidative stress, and disruption of genes including the heat shock factor hsf-1 , the hypoxia-inducible factor hif-1 , and the insulin/IGF-1 pathway components daf-2 , age-1 , and daf-16 all alter lifespan distributions by an apparent stretching or shrinking of time. To produce such temporal scaling, each intervention must alter to the same extent throughout adult life all physiological determinants of the risk of death. Organismic ageing in Caenorhabditis elegans therefore appears to involve aspects of physiology that respond in concert to a diverse set of interventions. In this way, temporal scaling identifies a novel state variable, r ( t ), that governs the risk of death and whose average decay dynamics involves a single effective rate constant of ageing, k r . Interventions that produce temporal scaling influence lifespan exclusively by altering k r . Such interventions, when applied transiently even in early adulthood, temporarily alter k r with an attendant transient increase or decrease in the rate of change in r and a permanent effect on remaining lifespan. The existence of an organismal ageing dynamics that is invariant across genetic and