The impact of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men

Abstract

BackgroundThe exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre‐frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men.MethodsRecreationally active young adult (20–30 yo; YA); active (ACT) and sedentary (SED) middle‐age (50–65 yo; MA‐ACT and MA‐SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre‐frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type‐specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type‐specific lipid content (by quantifying the Oil Red O stain intensity).ResultsOnly 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA‐SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre‐frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects.ConclusionsTaken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre‐frailty was observed.

Skeletal muscle wasting in chronic heart failure

“…47 The prevalence of sarcopenia in CHF patients is higher at 20% compared with control subjects of the same age. 50,51 In CHF, divergent anti-oxidative and metabolic but similar catabolic responses, i.e. 49 This particularly high incidence may be due to mitochondrial dysfunction combined with an abnormal energy metabolism and a transition of type I to type II myofibres.…”

Contemporary publication patterns in the Journal of Cachexia, Sarcopenia and Muscle by type and sub‐speciality: facts and numbers

“…[12][13][14][15][16][17] In the area of translational studies in the mechanisms of cachexia, studies were published on expression of spliced skeletal muscle genes, 18 along with scientific evaluations of skeletal muscle physiology, 19,20 growth, wasting, 21-23 preservation, 24,25 and regeneration. For the first time, the journal was seeing Cochrane reviews of the evidence base for interventions in cachexia and related fields coming through.…”

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Introduction

The Journal of Cachexia, Sarcopenia and Muscle (JCSM) has progressed significantly in the past three years, not only both in terms of its number of submitted and published articles but also in terms of greater impact, reaching an Impact Factor of over 12 in the most recently published analyses by Clarivate Analytics. [12][13][14][15][16][17] In the area of translational studies in the mechanisms of cachexia, studies were published on expression of spliced skeletal muscle genes, 18 along with scientific evaluations of skeletal muscle physiology, 19,20 growth, wasting, 21-23 preservation, 24,25 and regeneration. We conducted an analysis of the types of publications in the respective medical sub-specialities that this major cachexia focussed journal, JCSM, has published in the last three calendar years and analysed trends within each sub-discipline.

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Mitochondrial respiratory chain deficiency in older men and its relationship with muscle mass and performance

“…Brierley et al similarly found a positive correlation between age and the presence of COX -fibres in VL biopsies from a sample of 49 participants aged 21-95 years, including no evidence of negative fibres in those aged under 64 years [11]. The overall activity of SDH on histochemistry has also been found to decline across adulthood, although maintenance of regular physical activity may prevent this decline [15].There has been less investigation of whether respiratory chain deficiency is more common in muscle in people with sarcopenia, as recently defined by the EWGSOP. However, a previous case series of nine patients at mean age 71 demonstrated that mitochondrial myopathy can present later in life, with biopsy findings showing a characteristic COX -/ SDH ++ pattern that was not seen in controls [16].…”