Abstract
BackgroundPreclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.Methodology/Principal FindingsCommunity-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R2 = 0.78; Q2 = 0.61) as well as gait speed (R2 = 0.81; Q2 = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).Conclusions/SignificanceData from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.
Highlights
IntroductionThe 75+ years age group has been the most rapidly expanding segment of the population in Western countries [1]
Over the past decades, the 75+ years age group has been the most rapidly expanding segment of the population in Western countries [1]
Preclinical studies have implicated apoptosis in skeletal myocytes as a mechanism contributing to sarcopenia
Summary
The 75+ years age group has been the most rapidly expanding segment of the population in Western countries [1] This group is the most susceptible to developing functional impairments and disability [2]. The biological determinants of muscle aging remain elusive; several lines of evidence suggest that acceleration of apoptosis in skeletal myocytes during aging may represent a converging mechanism through which sarcopenia and physical function decline ensue (reviewed in [7]). The genetic characterization of interleukin 10-deficient mice, a rodent model of frailty, unveiled up-regulation of several skeletal muscle apoptosis-related genes [23], further supporting the involvement of accelerated myocyte apoptosis in the pathogenesis of sarcopenia and physical frailty in late life. We investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons
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