Charlotte H. Pion

Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans

Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial‐mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±sd) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3‐fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)‐positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage‐dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial‐mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.—Gouspillou, G., Sgarioto, N., Kapchinsky, S., Purves‐Smith, F., Norris, B., Pion, C. H., Barbat‐Artigas, S., Lemieux, R, Taivassalo, T., Morais, J. A., Aubertin‐Leheudre, M., Hepple, R. T. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 28, 28–1621 (1633). www.fasebj.org

Exploring the Role of Muscle Mass, Obesity, and Age in the Relationship Between Muscle Quality and Physical Function

BACKGROUND Divergent conclusions emerge from the literature regarding the relationship between muscle quality (defined as muscle strength per unit of muscle mass) and physical function. These contrasted results may be due to the influence of factors such as age, obesity, and muscle mass itself. Consequently, the aim of the present study was to explore the role of these factors in the relationship between muscle quality (MQ) and physical function. METHODS Data are from 312 individuals (97 men and 215 women) aged 50 years and older. Body composition (dual energy X-ray absorptiometry) and knee extension strength of the right leg (1 repetition maximum) were assessed. Appendicular lean body mass index (AppLBMI) and MQ (knee extension strength /right leg lean mass) were calculated. A composite score of physical function was created based on the timed up-and-go, alternate step, sit-to-stand, and balance tests. RESULTS MQ was significantly associated with physical function when AppLBMI (β = 0.179; P = .004) and body mass index (BMI) (β = 0.178; P = .003), but not age (β = 0.065; P = .26), were included in regression analysis. AppLBMI (β = 0.221; P < .001), BMI (β = 0.234; P < .001), and age (β = 0.134; P = .018) significantly interacted with MQ to determine physical function. CONCLUSIONS Our results show that muscle mass, obesity, and age influence the relationship between MQ and physical function, suggesting that these factors should be taken into account when interpreting MQ. Even so, higher levels of MQ were associated with higher physical function scores. Nutritional and physical activity interventions may be designed in this regard.

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

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.

Denervation drives mitochondrial dysfunction in skeletal muscle of octogenarians

Mitochondria are frequently implicated in the ageing of skeletal muscle, although the role of denervation in modulating mitochondrial function in ageing muscle is unknown. We show that increased sensitivity to apoptosis initiation occurs prior to evidence of persistent denervation and is thus a primary mitochondrial defect in ageing muscle worthy of therapeutic targeting. However, at more advanced age, mitochondrial function changes are markedly impacted by persistent sporadic myofibre denervation, suggesting the mitochondrion may be a less viable therapeutic target.

Toward a sex-specific relationship between muscle strength and appendicular lean body mass index?

BackgroundIn spite of some dissociation between muscle mass and strength, muscle strength is often used as a proxy to identify individuals with low muscle mass (sarcopenia). Thus, the aim of the present study was to investigate the relationship between muscle strength and the appendicular lean body mass index (app LBMI).MethodsOne hundred and five individuals were recruited. Knee extension and handgrip strength were measured. Body composition was assessed by DXA. App LBMI was calculated as appendicular lean body mass divided by height squared.ResultsAt le level of the entire cohort, both handgrip (r = 0.73; p < 0.001) and knee extension strength (r = 0.57; p < 0.001) were associated with app LBMI. However, in women, knee extension strength (r = 0.32; p < 0.05) but not handgrip strength (r = 0.14; p = 0.35) was associated with app LBMI; while in men, handgrip strength (r = 0.43; p < 0.01) but not knee extension strength (r = 0.27; p = 0.09) was associated with app LBMI.ConclusionsMuscle strength appears to be associated with lean body mass; however, handgrip strength may be preferentially used in men and knee extension strength in women to detect sarcopenic individuals. Future larger studies are now needed to confirm our findings and their clinical relevance.

Is handgrip strength normalized to body weight a useful tool to identify dynapenia and functional incapacity in post-menopausal women?

ABSTRACT Objective To investigate whether handgrip strength normalized to body weight could be a useful clinical tool to identify dynapenia and assess functional capacity in post-menopausal women. Method A total of 136 postmenopausal women were recruited. Body composition (Dual Energy X-ray Absorptiometry [DEXA], Bio-electrical Impedence Analysis [BIA]), grip strength (dynamometer) and functional capacity (senior fitness tests) were evaluated. Dynapenia was established according to a handgrip strength index (handgrip strength divided by body weight (BW) in Kg/KgBW) obtained from a reference population of young women: Type I dynapenic (<0.44 kg/KgBW) and type II dynapenic (<0.35 kg/KgBW). Results The results show a positive correlation between handgrip strength index (in kg/KgBW) and alternate-step test (r=0.30, p<0.001), chair-stand test (r=0.25, p<0.005) and one-leg stance test (r=0.335, p<0.001). The results also showed a significant difference in non-dynapenic compared to type I dynapenic and type II dynapenic for the chair-stand test (Non-dynapenic: 12.0±3.0; Type I: 11.7±2.5; Type II: 10.3±3.0) (p=0.037 and p=0.005, respectively) and the one-leg stance test (Non-dynapenic: 54.2±14.2; Type I: 43.8±21.4; Type II: 35.0±21.8) (p=0.030 and p=0.004, respectively). Finally, a significant difference was observed between type II dynapenic and non-dynapenic for the chair-stand test (p=0.032), but not with type I dynapenic. Conclusion The results showed that handgrip strength was positively correlated with functional capacity. In addition, non-dynapenic women displayed a better functional status when compared to type I and type II dynapenic women. Thus, the determination of the handgrip strength thresholds could be an accessible and affordable clinical tool to identify people at risk of autonomy loss.

Muscle strength and force development in high- and low-functioning elderly men: Influence of muscular and neural factors

Background Aging leads to a loss of muscle strength and functional capacity likely resulting from a combination of neural and muscle alterations. The aim of this study was to identify possible disparities in muscle strength and force development profiles in high‐ and low‐functioning elderly men and to investigate muscular and neurophysiological factors that could explain the differences. Methods Sixty community‐dwelling men in good general health were divided in two groups based on a functional capacity (FC) z‐score derived from 6 tests of the Short Physical Performance Battery and Senior Fitness Test (Normal and fast 4 m‐walk tests, normal and fast Timed‐up and go, chair and stair tests). Extensor strength of the lower limbs (LL) was obtained for concentric (CLES) contraction and combined with lean masses of LL (LLLM) to yield concentric (CLES/LLLM) index. Similarly, extensor strength of the right Quadriceps Femoris (IKES) was obtained during maximal voluntary isometric contraction (MVC) and combined with right thigh lean mass (rTLM) to produce an isometric strength (IKES/rTLM) index. A muscular profile was obtained from: ascending and descending force slopes during the MVC; Vastus Lateralis (VL) muscle twitches parameters (amplitude, contraction and ½ relaxation times); the knee joint velocity (KV) as well as integrated EMG (iEMG) were determined for a sit‐to‐stand functional evaluation; muscle phenotype. A neurophysiological profile was established from: the spinal excitability (Hmax/Mmax ratio); motoneuron conduction velocity (CV); the completeness of muscle activation (% of force reserve), median power frequency (MPF) and mean amplitude (MA) of the VL EMG signal during MVC. Results Coincidently, age did not differ between groups. Strength and force indices, descending force slopes for MVC, KV and iEMG during the sit‐to‐stand evaluation and FC parameters were all significantly (p < 0.05) lower in the LoFC group than in the HiFC group. In contrast, no difference was observed between groups in: LLLM and rTLM, Hmax/Mmax ratio, CV, twitch parameters and muscle phenotype. Conclusion The lower concentric and isometric strengths found in the LoFC group could not be accounted for by muscular factors. Similarly, peripheral nervous systems alterations could not explain group differences. It can be suggested that modifications within the central nervous system may be responsible for the differences in the functional status of healthy elderly individuals. Finally, more complex and demanding tasks, such as those requiring greater intensity or coordination, may further clarify how healthy elderly individuals with low and high functional capacities differ. HighlightsLow‐functioning elderly men had difficulty initiating a functional movementFunctional level was unrelated to muscular factorsSlower maximal force release is associated with low functional levelCentral nervous system inhibition was greater for low‐functioning elderly men