Life Sciences Research for Lifelong Health

Ageing

Ageing is probably the biggest challenge to healthcare systems in the first world, and the focus of major scientific initiatives. Ageing is normally viewed as a slow, inevitable decline in fitness, but the reality is more complex. It remains unclear why closely related organisms age at different rates, and why diet and lifestyle have such potent effects on longevity. The identification of mutations which extend healthy lifespan in a variety of organisms shows that there is a strong genetic component to ageing, but the interplay between genetic and environmental factors which appears to govern ageing remains mysterious.

Yeast is a widely used model system for ageing; this experimentally tractable model organism has an ageing process with remarkable similarities to higher eukaryotes.

We are using yeast to define genetic and environments contributions to ageing, and the transcriptional and phenotypic outcomes of these contributions.

We have refined existing methods to purify and characterise ageing cells and are constructing reference transcriptomes and epigenomes during ageing.

Our preliminary data suggests that ageing even in simple unicellular eukaryotes is a far more complex process than currently believed, encompassing a mixture of regulated and unavoidable changes.

Detangling this mixture of pathways is a critical aim, and understanding how the individual pathways can be modulated by diet and drugs is of particular interest.
We are also trying to understand how ageing affects microorganisms. This esoteric-sounding question is important as many of the biochemical pathways known to influence longevity evolved in our unicellular ancestors. We suspect that ageing does not cause an inevitable decline in fitness of microorganisms as it does in higher eukaryotes.

If so, then these ancient biochemical pathways evolved to control ageing for other purposes, and to understand how to manipulate the complex networks underlying ageing, it would be very helpful to understand what these pathways evolved to do.

We have found that ageing actually enhances the ability of yeast to capitalise on environmental changes, showing that pathways which alter the rate of ageing will also impact the robustness of an organism to environmental fluctuation. This idea is encapsulated in out ACTIVE hypothesis of ageing (Ageing Cells Thrive In Variable Environments).

This hypothesis provides a framework for understanding how individual cells respond to ageing, based on the assumption that ageing in higher eukaryotes represents the sum of many different changes occurring in different cell types and cannot necessarily be addressed as a single process.