Award details

Signalling mechanisms that determine the rate of ageing

Reference	BBS/E/B/000C0433
Principal Investigator / Supervisor	Dr Simon Cook
Co-Investigators / Co-Supervisors	Dr Michael Coleman, Dr Oliver Florey, Dr Phillip Hawkins, Dr Nicholas Ktistakis, Dr Hayley Sharpe, Professor Len Stephens, Dr Heidi Welch
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	3,727,794
Status	Current
Type	Institute Project
Start date	01/04/2017
End date	31/03/2023
Duration	59 months

Abstract

Ageing can be driven by the accumulation of senescent cells in a tissue causing the emergence of a SASP phenotype (Senescence-Associated Secretory Phenotype) in which senescent cells drive more senescence and loss of tissue function. Ageing can also be driven by loss of cells, including those lost by specific programmed cell death mechanisms. Age related loss of axons and synapses is a major contributor to frailty in old age. Not only does it reduce neuromuscular strength but it impairs vision, memory, cognition and many other functions. Each requires functional innervation and malfunctions when axons are lost. Our work has delineated an ancient axonal survival pathway that appears to detect damage by sensing intracellular NMN levels. If NMN levels rise, something that is normally prevented by NMNAT2-mediated conversion to NAD+, a signalling pathway involving SARM1 is engaged that culminates in axon death. We have provided evidence this pathway, in which NMNAT2 acts as a survival-factor and SARM1 as death-inducer, contributes to neurone loss seen in ageing. We have data indicating neutrophils can sense nerve damage and the emergence of SASP, suggesting their accumulation could be an early biomarker and may shape the progression of these age-related problems. Recent work has indicated there is a DNA-methylation “clock” that marks human age. The Epigenetics ISP has evidence the apparent age of this “clock” in cultured cells can be reset by brief treatment with rapamycin via an unknown mechanism.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Ageing, Neuroscience and Behaviour
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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