Discovering principles of senescent pathophysiology using a simple animal model
Description: Investigations of genes that affect lifespan have yielded many insights into the regulation of ageing, but have fallen short of identifying the mechanisms of ageing themselves. We have developed a new approach to investigating ageing which uses senescent pathology instead of lifespan as a metric for ageing in Caenorhabditis elegans. This pathology-centred approach examines (i) the causes of individual pathologies, and (ii) the diseases that limit lifespan. Our findings support a new ageing paradigm: the senescent pathologies studied result not from random damage, but from pathogenic run-on of wild-type function (or hyper-function). Such run-on is promoted by pathways that control ageing, e.g. insulin/IGF-1 signaling (IIS). The proposed work will pursue new leads generated by the pathology-centred approach. We shall ask: first, how does yolk production cause late-life disease, and how does IIS promote this? Second, how do different pathways controlling lifespan act by altering different causes of mortality? Third, is extended lifespan in C. elegans attributable to reproductive strategies specific to this species? This work will identify the steps in the causal chain between genes and lifespan, with the aim of establishing general principles of senescent pathophysiology that can guide research on the origins of diseases of human ageing.
Funder: Wellcome Trust
Amount: £1,154,000
Funding type: research
Funder scheme: Investigator Award in Science
Start date: 2019-10-01
End date: 2026-09-30
Investigator: Prof David H Gems
Institution: University College London
Funded outputs count: 36
Funder award ID: 215574/Z/19/Z
OpenAlex ID: G3745556292