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The effect of inter-individual variability in stress responses during ageing

Reference	BBS/E/B/000Z0046
Principal Investigator / Supervisor	Dr Maria Casanueva
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	47,189
Status	Current
Type	Institute Project
Start date	01/11/2013
End date	31/10/2017
Duration	48 months

Abstract

Ageing was once regarded as a random and progressive decline, until ground-breaking work in the nematode Caenorhabditis elegans demonstrated that a number of pathways control longevity, including insulin signaling pathway. Despite been genetically controlled, life expectancy is variable in many organisms, including laboratory strains of C. elegans, that lack genetic variability. The ageing process is exquisitely sensitive to protein folding homeostasis in the cell and molecular chaperones, key targets of insulin signaling pathway, are pivotal to this process by refolding proteins misfolded by genetic and/or environmental stressors. Despite its essentiality, it has been shown that chaperone’s transcription is highly stochastic across species. Moreover, we have previously demonstrated that inter-individual variation in chaperone expression in C. elegans is a good predictor of both stress resistance and mutation penetrance. We think that part of the mechanism that leads to lifespan variability is related to the inter-individual variability of chaperones and other genes that modulate longevity. We are interested in understanding what are the causes underlying inter-individual variability in the longevity pathways. A clue comes from the observation that the level of chaperone expression is passed through at least one generation. Because trans-generational memory in adaptation is usually associated with epigenetic mechanisms, these new findings suggest that at least part of the variability is related to chromatin modifications. In addition, we are interested in using sophisticated statistical tools to develop early biomarkers that can perform as predictors of lifespan as well as health-span. We think that the questions that we are addressing will get us closer to understanding what makes us different as individuals and how these differences influence the way we age.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Ageing
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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