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

Abstract

Background: The 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.

Methods: Recreationally 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).

Results: Only 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.

Conclusions: Taken 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.

Keywords: Atrophy; Exercise; Human muscle ageing; Lipid content; Mitochondria; Sarcopenia.

Figure 1

Effects of ageing, physical activity, and pre‐frailty on skeletal muscle fibre size. (A to F) Quantifications of the overall (A), type I (B), IIa (C), IIx (D), I/IIa (E), and IIa/IIx (F) fibre cross‐sectional area (CSA) of the vastus lateralis muscle of young adult (YA), active (Act), and sedentary (SED) middle‐aged (MA‐ACT and MA‐SED) and old (65 + yo; 65 + ACT and 65 + SED) and pre‐frail old (65 + PF) men. (G) Relationship between type I, IIa, and IIx fibre size area and the age of all of the participants. (A to F) present individual data as well as box and whisker plots. *p < 0.05 and q < 0.20.

Figure 2

Effects of ageing, physical activity, and pre‐frailty on skeletal muscle fibre type proportion. (A to F) Quantifications of the proportion of type I (A), IIa (B), IIx (C), I/IIa (D), IIa/IIx (E), and I/IIa + IIa/IIx (all hybrid fibre types) fibre of the vastus lateralis muscle of young adult (YA), active (ACT), and sedentary (SED) middle‐aged (MA‐ACT and MA‐SED) and old (65 + yo; 65 + Act and 65 + SED) and pre‐frail old (65 + PF) men. (A to F) present individual data as well as box and whisker plots. *p < 0.05 and q < 0.20.

Figure 3

Effects of ageing, physical activity, and pre‐frailty on the overall and fibre type specific mitochondrial content. (A to E) Quantifications of the overall (A), type I (B), IIa (C), IIx (D), IIa/IIx (E), succinate dehydrogenase (SDH) stain intensity of the vastus lateralis muscle of young adult (YA), active (ACT), and sedentary (SED) middle‐aged (MA‐Act and MA‐SED) and old (65 + yo; 65 + ACT and 65 + SED) and pre‐frail old (65 + PF) men. (F) Relationship between the mitochondrial content of type I, IIa, and IIx fibres and the age of all of our participants. (A to D) present individual data as well as box and whisker plots. *p < 0.05 and q < 0.20.

Figure 4

Effects of ageing, physical activity, and pre‐frailty on the overall and fibre type specific lipid content. (A to E) Quantifications of the overall (A), type I (B), IIa (C), IIx (D), IIa/IIx (E), Oil Red O stain intensity of the vastus lateralis muscle of young adult (YA), active (ACT), and sedentary (SED) middle‐aged (MA‐ACT and MA‐SED) and old (65 + yo; 65 + ACT and 65 + SED) and pre‐frail old (65 + PF) men. (F) Relationship between the lipid content of type I, IIa, and IIx fibres and the age of all of our participants. (A to D) present individual data as well as box and whisker plots. *p < 0.05 and q < 0.20.

Figure 5

Relationships between the overall mitochondrial content (SDH stain intensity) and indices of muscle function, functional capacities, and insulin sensitivity.