Major breakthroughs in medical care have led to a dramatic increase in human life expectancy over the last century. Unfortunately, all organisms age. Ageing leads to a decline in health with the last phase of human life being associated with morbidity and diseases. A key challenge in reducing late life morbidity lies in properly understanding why lifespan differences occur between individuals sharing the same genetic and environmental background. Put simply, although the effects of genetic and environmental factors on aging have been studied extensively, the impact of non-genetic factors are poorly understood. Towards this goal, a multidisciplinary team led Nadia Vertti-Quintero and colleagues from ETH Zürich and the University of Buffalo sought to unravel the reasons behind observed aging differences in the model organism Caenorhabditis elegans. (C. elegans) is perfectly suited for such studies since it is small, has a total lifespan of between 3 and 4 weeks and can be maintained in a genetically uniform population under controlled environmental conditions. The team studied heterogeneity in heat-shock response (HSR) - an effect in a specfic protein in C. elegans after being temporarily exposed to high temperatures - as an indicator for lifespan variability.
Novel microfluidic devices were developed to allow cross-sectional and longitudinal measurement of HSR dynamics at high throughput and with high resolution at population, sub-population and individual level. They further adapted a mathematical model of HSR to individual organisms and identified that model parameters associated with protein turnover are major drivers of variability in HSR dynamics. Based on these findings, the authors sorted and isolated sub-populations of C. elegans according to HSR capacity and showed that a higher HSR capacity in early adulthood correlates to a longer mean lifespan. They also found that even though protein turnover resets in embryos, the age of the mother nematodes affects average HSR capacity and HSR variability in embryos – presumably due differences in packaging of nutrients, mRNA and proteins from mother to egg.
Written by Prerit Mathur
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