Open AccessLongevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake
Author(s) -
Sharples Adam P.,
Hughes David C.,
Deane Colleen S.,
Saini Amarjit,
Selman Colin,
Stewart Claire E.
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12342
Subject(s) - longevity , biology , calorie restriction , skeletal muscle , ampk , mtorc1 , endocrinology , pi3k/akt/mtor pathway , mechanistic target of rapamycin , medicine , microbiology and biotechnology , genetics , signal transduction , protein kinase a , phosphorylation
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 ( SIRT s) 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 / TSC 2/ SIRT 1) 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.