Proteostasis and ageing: insights from long-lived mutant mice

Sands, W. A., Page, M. M. and Selman, C. (2017) Proteostasis and ageing: insights from long-lived mutant mice. Journal of Physiology, 595(20), pp. 6383-6390. (doi: 10.1113/JP274334) (PMID:28718225) (PMCID:PMC5638872)

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The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)-induced unfolded protein response (UPR), the ubiquitin-proteasome system (UPS) and autophagy, all appear indispensable for longevity in many long-lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long-lived mouse mutants have been described, many of which carry single-gene mutations within the growth-hormone, insulin/IGF-1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long-lived mouse mutants.

Item Type:Articles
Additional Information:CS acknowledges support from the Biotechnology and Biological Sciences Research Council (BBSRC) through the award of a New Investigator Grant (BB/H012850/1), and from the College of Medical, Veterinary and Life Sciences, University of Glasgow.
Glasgow Author(s) Enlighten ID:Selman, Professor Colin and Sands, Dr William
Authors: Sands, W. A., Page, M. M., and Selman, C.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Journal of Physiology
ISSN (Online):1469-7793
Published Online:17 July 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Physiology 595(20): 6383-6390
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
638451Dissecting the mechanisms underlying lifespan extension in insulin signalling mutant miceColin SelmanBiotechnology and Biological Sciences Research Council (BBSRC)BB/H012850/2RI BIODIVERSITY ANIMAL HEALTH & COMPMED