Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake

Aging Cell

Adam P. Sharples²  David C. Hughes²  Colleen S. Deane¹  Amarjit Saini⁴  Colin Selman³ 

[1] MRC/ARUK Centre of Excellence for Musculoskeletal Ageing Research, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK;Stem Cells, Ageing & Molecular Physiology Unit, Research Institute for Sport and Exercise Sciences (RISES), Exercise Metabolism and Adaptation Research Group (EMARG), Liverpool John Moores University, Tom Reilly Building, Liverpool, UK;Glasgow Ageing Research Network (GARNER), Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK;Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

关键词: AKT;    AMPK;    cachexia;    calorie restriction;    FOXO;    high‐protein diets;    IGF‐I;    IRS‐1;    lifespan;    longevity;    MAFBx;    mTOR;    MURF;    regeneration;    sarcopenia;    satellite cells;    SIRT;    SkM;    TSC;   

DOI  :  10.1111/acel.12342

来源: Wiley

【 摘 要 】

Summary

Advancing age is associated with a progressive loss of skeletal muscle (SkM) mass and function. Given the worldwide aging demographics, this is a major contributor to morbidity, escalating socio-economic costs and ultimately mortality. Previously, it has been established that a decrease in regenerative capacity in addition to SkM loss with age coincides with suppression of insulin/insulin-like growth factor signalling pathways. However, genetic or pharmacological modulations of these highly conserved pathways have been observed to significantly enhance life and healthspan in various species, including mammals. This therefore provides a controversial paradigm in which reduced regenerative capacity of skeletal muscle tissue with age potentially promotes longevity of the organism. This paradox will be assessed and considered in the light of the following: (i) the genetic knockout, overexpression and pharmacological models that induce lifespan extension (e.g. IRS-1/s6K KO, mTOR inhibition) versus the important role of these signalling pathways in SkM growth and adaptation; (ii) the role of the sirtuins (SIRTs) in longevity versus their emerging role in SkM regeneration and survival under catabolic stress; (iii) the role of dietary restriction and its impact on longevity versus skeletal muscle mass regulation; (iv) the crosstalk between cellular energy metabolism (AMPK/TSC2/SIRT1) and survival (FOXO) versus growth and repair of SkM (e.g. AMPK vs. mTOR); and (v) the impact of protein feeding in combination with dietary restriction will be discussed as a potential intervention to maintain SkM mass while increasing longevity and enabling healthy aging.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.