Key points The maintenance of optimal mitochondrial content and function is critical for muscle health. Mitochondrial dynamics play key roles in mitochondrial quality control; however, the exact role that mitochondrial fission plays in skeletal muscle health remains unclear. Here we report knocking down Drp1 (a protein regulating mitochondrial fission) for 4 months in adult mouse skeletal muscle resulted in severe muscle atrophy (40–50%). Drp1 knockdown also led to a reduction in ADP‐stimulated respiration, an increase in markers of impaired autophagy and increased muscle regeneration, denervation, fibrosis and oxidative stress. Our data indicate that Drp1 is crucial for the maintenance of normal mitochondrial function and that Drp1 depletion severely impairs muscle health. Abstract Mitochondria play central roles in skeletal muscle physiology, including energy supply, regulation of energy‐sensitive signalling pathways, reactive oxygen species production/signalling, calcium homeostasis and the regulation of apoptosis. The maintenance of optimal mitochondrial content and function is therefore critical for muscle cells. Mitochondria are now well known as highly dynamic organelles, able to change their morphology through fusion and fission processes. Solid experimental evidence indicates that mitochondrial dynamics play key roles in mitochondrial quality control, and alteration in the expression of proteins regulating mitochondrial dynamics have been reported in many conditions associated with muscle atrophy and wasting. However, the exact role that mitochondrial fission plays in skeletal muscle health remains unclear. To address this issue, we investigated the impact of Drp1 (a protein regulating mitochondrial fission) knockdown, introduced via intramuscular injection of adeno‐associated virus (AAV) on adult mouse skeletal muscle. Knocking down Drp1 for 4 months resulted in very severe muscle atrophy (40–50%). Drp1 knockdown also led to a reduction in ADP‐stimulated respiration and increases in markers of muscle regeneration, denervation, fibrosis, oxidative stress and impaired autophagy. Our findings indicate that Drp1 is essential for the maintenance of normal mitochondrial function and that Drp1 suppression severely impairs muscle health.

Background: To compare the effects of high-intensity interval training (HIIT) alone vs. HIIT combined with L-citrulline (CIT) supplementation on functional capacity and muscle function in dynapenic-obese elderly. Methods: A total of 56 obese (fat mass: men > 25%, women > 35%) and dynapenic (grip strength/body weight: women < 0.44, men < 0.61) subjects were recruited and divided in two groups: HIIT+CIT (n = 26; age: 6 5 ± four years) vs. HIIT+Placebo (PLA, n = 30; age: 68 ± four years). Participants followed a 12-week HIIT using an elliptical trainer. Participants took a single and isocaloric 10 g-dose of CIT or PLA every day. Body composition; functional and aerobic capacities; absolute or relative upper and lower limbs muscle strength, muscle power; and energy balance were measured pre and post intervention. Results: Both groups significantly improved functional capacity and muscle function. However, HIIT+CIT demonstrated greater improvements in fast-paced Timed Up & Go (p = 0.04) and upper limbs muscle strength (absolute and relative) (p = 0.05) than HIIT+Placebo. Conclusion: CIT supplementation when combined with HIIT seems to induce greater improvements in upper limbs muscle strength and walking speed in dynapenic-obese elderly. Further studies are needed to confirm our results, to elucidate the mechanisms underlying the beneficial effects of CIT and to define the long-term impact of CIT/HIIT.

Background Aging is associated with a progressive decline in skeletal muscle mass and strength as well as an increase in adiposity. These changes may have devastating impact on the quality of life of older adults. Mitochondrial dysfunctions have been implicated in aging-related and obesity-related deterioration of muscle function. Impairments in mitochondrial quality control processes (biogenesis, fusion, fission, and mitophagy) may underlie this accumulation of mitochondrial dysfunction. High-intensity interval training (HIIT) was shown to improve muscle and mitochondrial function in healthy young and old adults and to improve body composition in obese older adults. Recent studies also positioned citrulline (CIT) supplementation as a promising intervention to counter obesity-related and aging-related muscle dysfunction. In the present study, our objectives were to assess whether HIIT, alone or with CIT, improves muscle function, functional capacities, adipose tissue gene expression, and mitochondrial quality control processes in obese older adults. Methods Eighty-one-old and obese participants underwent a 12 week HIIT with or without CIT on an elliptical trainer [HIIT-CIT: 20 men/25 women, 67.2 ± 5.0 years; HIIT-placebo (PLA): 18 men/18 women, 68.1 ± 4.1 years]. Handgrip and quadriceps strength, lower limb muscle power, body composition, waist circumference, and functional capacities were assessed pre and post intervention. Vastus lateralis muscle biopsies were performed in a subset of participants to quantify markers of mitochondrial content (TOM20 and OXPHOS subunits), biogenesis (TFAM), fusion (MFN1&2, OPA1), fission (DRP1), and mitophagy (Parkin). Subcutaneous abdominal adipose tissue biopsies were also performed to assess the expression of genes involved in lipid metabolism. Results HIIT-PLA and HIIT-CIT displayed improvements in functional capacities (P < 0.05), total

Sarcopenia and obesity are considered a double health burden. Therefore, the implementation of effective strategies is needed to improve the quality of life of older obese individuals. The aim of this study was to compare the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on functional capacities, muscle function, body composition and blood biomarkers in obese older adults. Adipose tissue gene expression and markers of muscle mitochondrial content and quality control involved in exercise adaptations were also investigated. Sixty-eight participants performed either HIIT (n = 34) on an elliptical trainer or MICT (n = 34) on a treadmill, three times per week for 12 weeks. HIIT produced significantly higher benefits on some physical parameters (six-minute walking test (HIIT: +12.4% vs. MICT: +5.2%); step test (HIIT: +17.02% vs. MICT: +5.9%); ten-repetition chair test (HIIT: −17.04% vs. MICT: −4.7%)). Although both HIIT and MICT led to an improvement in lower limb power (HIIT: +25.2% vs. MICT: +20.4%), only MICT led to higher improvement in lower limb muscle strength (HIIT: +4.3% vs. MICT: +23.2%). HIIT was more beneficial for increasing total lean body mass (HIIT: +1.58% vs. MICT: −0.81%), while MICT was more effective for decreasing relative gynoid fat mass (HIIT: −1.09% vs. MICT: −4.20%). Regarding adipose tissue gene expression, a significant change was observed for cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in the HIIT group (A.U; HIIT at T0: 32.10 ± 39.37 vs. HIIT at T12: 48.2 ± 59.2). Mitochondrial transcription factor A (TFAM) content, a marker of mitochondrial biogenesis, increased significantly following HIIT (+36.2%) and MICT (+57.2%). A significant increase was observed in the HIIT group for Translocase of Outer Membrane 20 (TOM20; +54.1%; marker of mitochondrial content), Mitofusin-2 (MFN2; +71.6%; marker of mitochondrial fusion) and Parkin RBR E3 Ubiquitin Protein Ligase (PARKIN; +42.3%; marker of mitophagy). Overall, our results indicate that even though MICT (walking on treadmill) and HIIT (on an elliptical) are effective intervention strategies in obese older adults, HIIT appears to have slightly more beneficial effects. More specifically, HIIT led to higher improvements than MICT on functional capacities, lean mass and skeletal muscle markers of mitochondrial content, fusion, and mitophagy. Thus, MICT but also HIIT (time-efficient training) could be recommended as exercise modalities for obese older adults to maintain or improve mobility, health and quality of life.

Aging leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength [MS]/lean muscle mass [LM]). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (Age:69±7years; BMI:18-30kg.m-2) randomized into 3 groups: 1) Placebo+MPT (PLA; n=19); 2) F-PROT+MPT (n=21); 3) S-PROT+MPT (n=20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3-times/week;1h/session) combined with a supplement (30g: 10g per meal) of F-PROT (whey) or S-PROT (casein) or a Placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, and lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT per day to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above recommended daily allowance) amount of protein per day.

Background Aging is associated with declines in muscle mass, strength and quality, leading to physical impairments. An even protein distribution in daily meals has recently been proposed along with adequate total protein intake as important modulators of muscle mass. In addition, due to its short duration, high-intensity interval training (HIIT) has been highlighted as a promising intervention to prevent physical deterioration. However, the interaction between daily protein intake distribution and HIIT intervention in elderlies remain unknown. Objective To investigate muscle adaptation following HIIT in older adults according to daily protein intake distribution. Methods Thirty sedentary obese subjects who completed a 12-week elliptical HIIT program were matched [criteria: age (± 2 years), sex, BMI (± 2 kg/m 2 )] and divided a posteriori into 2 groups according to the amount of protein ingested at each meal: < 20 g in at least one meal (P20−, n = 15, 66.8 ± 3.7 years) and ≥ 20 g in each meal (P20+, n = 15, 68.1 ± 4.1 years). Body composition, functional capacity, muscle strength, muscle power, physical activity level, and nutritional intakes were measured pre-and post-intervention. A two way repeated ANOVA was used to determine the effect of the intervention (HIIT) and protein distribution (P20− vs P20+, p < 0.05). Results No difference was observed at baseline between groups. Following the HIIT intervention, we observed a significant decrease in waist and hip circumferences and improvements in functional capacities in both P20− and P20 + group (p < 0.05). However, no protein distribution effect was observed. Conclusion A 12-week HIIT program is achievable and efficient to improve functional capacities as well as body composition in obese older adults. However, consuming at least 20 g of proteins in every meal does not further enhance muscle performance in response to a 12-week HIIT intervention.

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ObjectiveTo 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. MethodA 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).ResultsThe 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.ConclusionThe 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.