How do somatic mutations contribute to aging? A test using insect model systems

The cause of ageing is a long-standing mystery in biology and medicine, but a popular hypothesis is that it results from the accumulation of mutations in somatic cells.

This hypothesis predicts an inverse correlation between rates of somatic mutations and longevity among multicellular organisms.

However, this prediction is largely untested due to experimental challenges in detecting somatic mutations on a genome scale with high fidelity.

Major insights into ageing can be gained from systems where individuals with the same genetic background differ greatly in lifespan.

Here we propose to study two examples of this: 1) honeybees, in which queens live more than an order of magnitude longer than worker bees and 2) experimental evolution lines of seed beetles that differ more than twofold in longevity. Both of these systems also exhibit profound differences in lifespan between sexes.

We will optimise recently-developed protocols for detecting mutations in single cells to test whether rates of somatic mutations differ between long-lived and short-lived individuals from the two study systems. We will analyse how somatic mutation rates change as individuals age and which mutational processes are responsible.

This project will lead to a greater understanding of why we age and the factors that govern mutations in somatic tissues.