Simons Lab

Why and how all life slowly deteriorates to eventually cause death

Living longer and healthier is a key objective of medical science. Many major life threatening diseases can be considered diseases of ageing. However, the biology of ageing remains one of the most intriguing, yet mechanistically least understood, aspects of life.

In addition, from an evolutionary perspective, ageing and associated trade-offs are central to the evolution of life history and hence biodiversity. A holistic understanding of ageing can thus provide fundamental insight into biology and translational knowledge for medical science.

Ageing is a difficult phenotype, because a lot goes amiss physiologically at the same time, and probably at heterogeneous rates in different cells and tissues. Therefore, we study the ultimate consequence of this multifaceted deterioration caused by ageing: death.

The risk to die follows specific patterns that can be used to implicate specific physiology and are quantitative and therefore ideal to test theoretical models, or to summarise using meta-analysis.

Another connected focus of the lab is the connection between diet and ageing. In flies, a reduction in protein in the diet results in a rapid (within 1–2 days) drop in mortality risk. This is a highly intriguing phenotype as it suggests physiological remodelling within the fly that instantly reduces mortality risk 6 to 7-fold.

We use functional genetics in flies to study the mechanisms of dietary restriction and other ways that could instantly reduce mortality risk. Such instant control of mortality is highly translational as it has the potential to instantly increase health- and lifespan at advanced age, without the need for lifelong interventions.

A graph indicating how in flies, a reduction in protein in the diet results in a rapid (within 1–2 days) drop in mortality risk.

Funded by

Natural Environment Research Council
The University of Sheffield
Wellcome Trust