Partial-body cryostimulation does not impact peripheral microvascular responsiveness but reduces muscular metabolic O2 consumption (mV˙O2) at rest.

This study aimed to investigate the effect of partial-body cryostimulation (PBC) on microvascular responsiveness and muscular metabolic O2 consumption rate (mV˙O2). Twenty healthy young adults (ten males and ten females) underwent a post-occlusive reactive hyperemia (PORH) test at the flexor digitorum superficialis area before and after a 3-min PBC session and a 3-min control session. Using near-infrared spectroscopy, occlusion and reperfusion slopes were calculated: oxyhemoglobin ([HbO2]) decrease rate ([HbO2] slope 1), deoxyhaemoglobin ([HHb]) increase rate ([HHb] slope 1), [HbO2] increase rate ([HbO2] slope 2), and [HHb] increase rate ([HHb] slope 2. Using HbO2 kinetics during the occlusion, mV˙O2 was also calculated to characterize myocytes' metabolic O2 consumption. HbO2 slope 1 value was lower after PBC than before PBC (-0.15 ± 0.08 vs -0.24 ± 0.11 s-1; respectively; P < 0.05) in male participants only. A lower [HHb] slope 1 was also observed after PBC compared to before PBC (0.18 ± 0.10 vs 0.24 ± 0.16 s-1; P < 0.05) with no interaction for sex categories. mV˙O2 was significantly lower after PBC than before (pre values 14.75 ± 3.94 vs 18.47 ± 5.73 µMO2Hb.s-1; respectively; P < 0.01) with no interaction between sex categories. No changes in the calculated slope 2 were observed. These findings suggest that a single session of PBC reduces the muscular metabolic O2 needs at rest; however, it does not alter the vascular ability to provide O2 to the myocytes.

Glucose 6-P Dehydrogenase Overexpression Improves Aging-Induced Endothelial Dysfunction in Aorta from Mice: Role of Arginase II.

The increase of vascular arginase activity during aging causes endothelial dysfunction. This enzyme competes with the endothelial nitric oxide synthase (eNOS) for L-arginine substrate. Our hypothesis is that glucose 6-P dehydrogenase (G6PD) overexpression could improve the endothelial function modulating the arginase pathway in aorta from mice. For this study, three groups of male mice were used: young wild type (WT) (6-9 months), old WT (21-22 months) and old G6PD-Tg (21-22 months) mice. Vascular reactivity results showed a reduced acetylcholine-dependent relaxation in the old WT but not old G6PD-Tg group. Endothelial dysfunction was reverted by nor-NOHA, an arginase inhibitor. Mice overexpressing G6PD underexpressed arginase II and also displayed a lower activity of this enzyme. Moreover, histological analyses demonstrated that age causes a thickness of aortic walls, but this did not occur in G6PD-Tg mice. We conclude that the overexpressing G6PD mouse is a model to improve vascular health via the arginase pathway.

Physical Activity Levels and Psychological Well-Being during COVID-19 Lockdown among University Students and Employees.

During the lockdown for the coronavirus disease 2019 (COVID-19), entire populations were instructed to live in home confinement. We investigated the effects of the COVID-19 lockdown on the physical activity (PA) and mental health of students and employees in a Colombian University. A cross-sectional study was conducted through an online survey during the first isolation. A total of 431 respondents (192 males) aged 18-60 years old (28.1 ± 11.1 years) participated. The international Physical Activity Questionnaire (IPAQ) and the short version of the Psychological General Well-Being Index (PGWBI-S) were used. The lockdown had a negative effect on PA levels, with students exhibiting the greatest decrease (~34%; p ˂ 0.001) compared to employees (~24%; p ˂ 0.01). The analysis showed a greater change in PA behavior before and during the lockdown in highly active student participants (5750 vs. 5141 MET min/week; p < 0.05). Additionally, the psychological assessment revealed a lower score in students compared to employees in the male (70.1 vs. 82.6) and female groups (60.2 vs. 79.6). Moreover, the results revealed an influence of sex, with only the female students exhibiting a state of distress. Self-reported PA and psychological well-being were compromised during the COVID-19 lockdown in the academic community, with students and females being more affected.

Glucose 6-P dehydrogenase delays the onset of frailty by protecting against muscle damage.

BACKGROUND: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. METHODS: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigated. RESULTS: The percentage of frail mice was significantly lower in the G6PD-Tg than in the WT genotype, especially in 26-month-old mice where 50% of the WT were frail vs. only 13% of the Tg ones (P < 0.001). Skeletal muscle transcriptomic analysis showed an up-regulation of respiratory chain and oxidative phosphorylation (P = 0.009) as well as glutathione metabolism (P = 0.035) pathways in the G6PD-Tg mice. Accordingly, the Tg animals exhibited an increase in reduced glutathione (34.5%, P < 0.01) and a decrease on its oxidized form (-69%, P < 0.05) and in lipid peroxidation (4-HNE: -20.5%, P < 0.05). The G6PD-Tg mice also showed reduced apoptosis (BAX/Bcl2: -25.5%, P < 0.05; and Bcl-xL: -20.5%, P < 0.05), lower levels of the intramuscular adipocyte marker FABP4 (-54.7%, P < 0.05), and increased markers of mitochondrial content (COX IV: 89.7%, P < 0.05; Grp75: 37.8%, P < 0.05) and mitochondrial OXPHOS complexes (CII: 81.25%, P < 0.01; CIII: 52.5%, P < 0.01; and CV: 37.2%, P < 0.05). Energy expenditure (-4.29%, P < 0.001) and the respiratory exchange ratio were lower (-13.4%, P < 0.0001) while the locomotor activity was higher (43.4%, P < 0.0001) in the 20-month-old Tg, indicating a major energetic advantage in these mice. Short-term exercise training in young C57BL76J mice induced a robust activation of G6PD in skeletal muscle (203.4%, P < 0.05), similar to that achieved in the G6PD-Tg mice (142.3%, P < 0.01). CONCLUSIONS: Glucose 6-P dehydrogenase deficiency can be an underestimated risk factor for several human pathologies and even frailty. By overexpressing G6PD, we provide the first molecular model of robustness. Because G6PD is regulated by pharmacological and physiological interventions like exercise, our results provide molecular bases for interventions that by increasing G6PD will delay the onset of frailty.

Physical exercise in the prevention and treatment of Alzheimer's disease.

Dementia is one of the greatest global challenges for health and social care in the 21st century. Alzheimer's disease (AD), the most common type of dementia, is by no means an inevitable consequence of growing old. Several lifestyle factors may increase, or reduce, an individual's risk of developing AD. Much has been written over the ages about the benefits of exercise and physical activity. Among the risk factors associated with AD is a low level of physical activity. The relationship between physical and mental health was established several years ago. In this review, we discuss the role of exercise (aerobic and resistance) training as a therapeutic strategy for the treatment and prevention of AD. Older adults who exercise are more likely to maintain cognition. We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies. We will pay especial attention to the potential role of exercise in the modulation of amyloid ß turnover, inflammation, synthesis and release of neurotrophins, and improvements in cerebral blood flow. Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide. Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.

Evaluation of an Antioxidant and Anti-inflammatory Cocktail Against Human Hypoactivity-Induced Skeletal Muscle Deconditioning.

Understanding the molecular pathways involved in the loss of skeletal muscle mass and function induced by muscle disuse is a crucial issue in the context of spaceflight as well as in the clinical field, and development of efficient countermeasures is needed. Recent studies have reported the importance of redox balance dysregulation as a major mechanism leading to muscle wasting. Our study aimed to evaluate the effects of an antioxidant/anti-inflammatory cocktail (741 mg of polyphenols, 138 mg of vitamin E, 80 µg of selenium, and 2.1 g of omega-3) in the prevention of muscle deconditioning induced by long-term inactivity. The study consisted of 60 days of hypoactivity using the head-down bed rest (HDBR) model. Twenty healthy men were recruited; half of them received a daily antioxidant/anti-inflammatory supplementation, whereas the other half received a placebo. Muscle biopsies were collected from the vastus lateralis muscles before and after bedrest and 10 days after remobilization. After 2 months of HDBR, all subjects presented muscle deconditioning characterized by a loss of muscle strength and an atrophy of muscle fibers, which was not prevented by cocktail supplementation. Our results regarding muscle oxidative damage, mitochondrial content, and protein balance actors refuted the potential protection of the cocktail during long-term inactivity and showed a disturbance of essential signaling pathways (protein balance and mitochondriogenesis) during the remobilization period. This study demonstrated the ineffectiveness of our cocktail supplementation and underlines the complexity of redox balance mechanisms. It raises interrogations regarding the appropriate nutritional intervention to fight against muscle deconditioning.

Modulating Oxidant Levels to Promote Healthy Aging.

Significance: Free radicals although originally thought of as damaging molecules, inevitable side effects of the utilization of oxygen by cells, are now considered as signals that by modifying, among others, the thiol-disulfide balance regulate many cell processes from metabolism to cell cycle. Recent Advances: This review discusses the importance of the modulation of the oxidant levels through physiological strategies such as physical exercise or genetic manipulations such as the overexpression of antioxidant enzymes, in the promotion of healthy aging. Critical Issues: We have divided the review into five different sections. In the first two sections of the article "Oxidants are signals" and "Exercise training is an antioxidant," we discuss the main sources of free radicals during muscle contraction and their role, as hormetic substances, in the regulation of two main muscle adaptations to exercise in skeletal muscle; that is, mitochondrial biogenesis and the endogenous antioxidant defense. In the third section of the review, we deal with "the energy collapse in aging." The increased rate of reactive oxygen species (ROS) production and the low rate of mitochondria biosynthesis in the old cells are examined. Finally, in the fourth and fifth sections entitled "Overexpression of antioxidants enzymes in healthy aging" and "Exercise, longevity, and frailty," we consider the importance of the potentiation of the cellular defenses in health span and in life span. Future Directions: A correct manipulation of the ROS generation, directing these species to their physiological signaling role and preventing their deleterious effects, would allow the promotion of healthy aging. Antioxid. Redox Signal. 33, 570-579.

Muscle Resting and TGF-ß Inhibitor Treatment Prevent Fatty Infiltration Following Skeletal Muscle Injury.

BACKGROUND/AIMS: Skeletal muscle injuries are the most common type of injury occurring in sports, and investigating skeletal muscle regeneration as well as understanding the related processes is an important aspect of the sports medicine field. The process of regeneration appears to be complex and precisely orchestrated, involving fibro-adipogenic progenitors (FAPs) which are a muscle-resident stem cell population that appears to play a major role in abnormal development of fibrotic tissue or intermuscular adipose tissue (IMAT). Our present study aims to investigate whether muscle resting or endurance exercise following muscle injury may change the behavior of FAPs and subsequently impact the development of fatty infiltrations and fibrosis, two hallmarks of regeneration failure. METHODS: We used the validated glycerol muscle injury model to mimic abnormal muscle regenerative conditions in mice. We challenged this specific regeneration model with hindlimb unloading or endurance exercise and, in a second set of experiments, we treated mice with decorin, a TGF-ß inhibitor. RESULTS: In this study, we demonstrated that: i) muscle resting just after injury leads to inhibition of IMAT development, ii) TNF-α mediated FAP apoptosis might be perturbed in this specific glycerol model of muscle injury, leading to IMAT development, and iii) treatment with the TGF-ß inhibitor decorin decreases IMAT development and might restores FAP apoptosis. CONCLUSION: In addition to the potential clinical relevance of decorin treatment in situations involving muscle plasticity and regeneration, this study also demonstrates that a period of muscle resting is necessary following muscle injury to achieve efficient muscle regeneration which is associated with a reduction in fatty infiltration. Unreasonably early resumption of exercise brings no gain to regeneration, further highlighting that this resting period is necessary.

Short-term disuse promotes fatty acid infiltration into skeletal muscle.

BACKGROUND: Many physiological and/or pathological conditions lead to muscle deconditioning, a well-described phenomenon characterized by a loss of strength and muscle power mainly due to the loss of muscle mass. Fatty infiltrations, or intermuscular adipose tissue (IMAT), are currently well-recognized components of muscle deconditioning. Despite the fact that IMAT is present in healthy human skeletal muscle, its increase and accumulation are linked to muscle dysfunction. Although IMAT development has been largely attributable to inactivity, the precise mechanisms of its establishment are still poorly understood. Because the sedentary lifestyle that accompanies age-related sarcopenia may favour IMAT development, deciphering the early processes of muscle disuse is of great importance before implementing strategies to limit IMAT deposition. METHODS: In our study, we took advantage of the dry immersion (DI) model of severe muscle inactivity to induce rapid muscle deconditioning during a short period. During the DI, healthy adult men (n = 12; age: 32 ± 5) remained strictly immersed, in a supine position, in a controlled thermo-neutral water bath. Skeletal muscle biopsies were obtained from the vastus lateralis before and after 3 days of DI. RESULTS: We showed that DI for only 3 days was able to decrease myofiber cross-sectional areas (-10.6%). Moreover, protein expression levels of two key markers commonly used to assess IMAT, perilipin, and fatty acid binding protein 4, were upregulated. We also observed an increase in the C/EBPα and PPARγ protein expression levels, indicating an increase in late adipogenic processes leading to IMAT development. While many stem cells in the muscle environment can adopt the capacity to differentiate into adipocytes, fibro-adipogenic progenitors (FAPs) represent the population that appears to play a major role in IMAT development. In our study, we showed an increase in the protein expression of PDGFRα, the specific cell surface marker of FAPs, in response to 3 days of DI. It is well recognized that an unfavourable muscle environment drives FAPs to ectopic adiposity and/or fibrosis. CONCLUSIONS: This study is the first to emphasize that during a short period of severe inactivity, muscle deconditioning is associated with IMAT development. Our study also reveals that FAPs could be the main resident muscle stem cell population implicated in ectopic adiposity development in human skeletal muscle.