Muscle Adaptation Research Articles

Physical exercise ameliorates age-related deterioration of skeletal muscle and mortality by activating Pten-related pathways in Drosophila on a high-salt diet.

The phosphatase and tensin congeners (Pten) gene affects cell growth, cell proliferation, and rearrangement of connections, and it is closely related to cellular senescence, but it remains unclear the role of muscle-Pten gene in exercise against age-related deterioration in skeletal muscle and mortality induced by a high-salt diet (HSD). In here, overexpression and knockdown of muscle Pten gene were constructed by building MhcGAL4 /PtenUAS-overexpression and MhcGAL4 /PtenUAS-RNAi system in flies, and flies were given exercise training and a HSD for 2 weeks. The results showed that muscle Pten knockdown significantly reduced the climbing speed, climbing endurance, GPX activity, and the expression of Pten, Sirt1, PGC-1α genes, and it significantly increased the expression of Akt and ROS level, and impaired myofibril and mitochondria of aged skeletal muscle. Pten knockdown prevented exercise from countering the HSD-induced age-related deterioration of skeletal muscle. Pten overexpression has the opposite effect on skeletal muscle aging when compared to it knockdown, and it promoted exercise against HSD-induced age-related deterioration of skeletal muscle. Pten overexpression significantly increased lifespan, but its knockdown significantly decreased lifespan of flies. Thus, current results confirmed that differential expression of muscle Pten gene played an important role in regulating skeletal muscle aging and lifespan, and it also affected the adaptability of aging skeletal muscle to physical exercise since it determined the activity of muscle Pten/Akt pathway and Pten/Sirt1/PGC-1α pathway.

Stuart has got the PoWeR! Skeletal muscle adaptations to a novel heavy progressive weighted wheel running exercise model in C57BL/6 mice.

Murine exercise models are developed to study the molecular and cellular mechanisms regulating muscle mass. A progressive weighted wheel running model, named 'PoWeR', was previously developed to serve as a more translatable alternative to involuntary resistance-type exercise models in rodents, such as synergist ablation. However, mice still run great distances despite the added resistance as evidenced by a large glycolytic-to-oxidative shift in muscle fibre type. Thus, PoWeR reflects a blended resistance/endurance model. In an attempt to bias PoWeR further towards resistance-type exercise, we developed a novel heavy PoWeR model (hPoWeR) utilizing higher wheel loads (max of 12.5g vs 6g). Adult male C57BL/6 mice voluntarily performed an 8-week progressive loading protocol (PoWeR or hPoWeR). Running distance peaked at ∼5-6kmday-1 in both treatments and was maintained by PoWeR mice, but declined in the hPoWeR mice as load increased beyond 7.5g. Peak isometric force of the gastrocnemius-soleus-plantaris complex tended to increase in wheel running treatments. Soleus mass increased by 19% and 24% in PoWeR and hPoWeR treatments, respectively, and plantaris fibre cross-sectional area was greater in hPoWeR, compared to PoWeR. There were fewer glycolytic and more oxidative fibres in the soleus and plantaris muscles in the PoWeR treatment, but not hPoWeR. Collectively, these data suggest hPoWeR may modestly alter skeletal muscle supporting the aim of better reflecting typical resistance training adaptations, in line with decreased running volume and exposure to higher resistance. Regardless, PoWeR remains an effective hypertrophic concurrent training model in mice.

Genetic and Physiological Predictors of Bioenergetic Adaptation Skeletal Muscles in Athletes of Cyclic Sports

When performing maximum loads, an important criterion for assessing prospects is the achievement of the best result with the least metabolic changes in the body of athletes, which indicates the possibility of further increasing physical performance. The study of the mechanisms of energy supply and the reaction of body systems when testing performance under special conditions is one of the important conditions for the development of additional biochemical criteria for assessing the prospects of athletes. Purpose: To study genetic and physiological predictors of bioenergetic adaptation of skeletal muscles in athletes of cyclic sports. Methods: 76 athletes of cyclic sports (speed skating, running disciplines in track-and-field) of European origin who lived in the Southern Urals region took part in the study. The average age of the study participants was 22.1 ± 2.5 y.o. Experience in sports was at least 5 years. We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. The study of bio-energetic indicators of athletes' physical performance was carried out using the bicycle ergometry method (test with maximum load). Biochemical studies were carried out using a Lactate Scout Plus lactometer. Results: Significant differences were found in the ΔLa (%) indicator: in athletes with a dominant homozygous genotype R/R, lactate clearance during a 10-minute rest after performing a bicycle ergometer load is statistically significantly higher than in athletes with a recessive homozygous genotype X/X (20.14±12.74%, versus 11.11±3.12%; p<0.05). The major allele C (R) was associated with moderate and high lactate clearance (OR = 2.25 [95% CI: 0.99 – 5.11] and OR = 2.24 [95% CI: 0.91 – 5.51], respectively). At the same time, a statistically significant association was identified between the minor allele T(X) and the homozygous genotype TT (XX) with low lactate clearance (OR = 12.14 [95% CI: 1.30 – 13.55]). High values of lactate clearance indicate the utilization of lactate from peripheral blood and more efficient recovery processes in carriers of the major allele C (R). Conclusions: lactate clearance during a 10-minute rest period after a bicycle ergometer test with maximum load and DNA profiling of the ACTN3 gene rs1815739 can be recommended as significant physiological and genetic predictors of bioenergetic adaptation of skeletal muscles in cyclical sports athletes of Caucasian origin in the Southern Urals.

Coordinated Regulation of Myonuclear DNA Methylation, mRNA, and miRNA Levels Associates With the Metabolic Response to Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy in Female Mice.

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth.

The effect of prolonged walking on leg muscle activity patterns and vulnerability to perturbations

Understanding the consequences and ecological relevance of muscle fatigue is important to guide the development of strategies to preserve independence. However, few studies have examined walking-related fatigue and the effects on walking instability. Our purpose was to investigate the effects of prolonged walking on leg muscle activity and vulnerability to balance perturbations. Eighteen healthy young adults completed a 30-min walking trial at their preferred walking speed while leg muscle activities were recorded. Before and after the 30-min walk, participants responded to five 5% body weight lateral force perturbations. Time-frequency analysis with wavelet transformation and principal component analyses assessed neuromuscular adaptations of muscles to prolonged walking. Following prolonged walking, we observed a time-dependent increase in EMG intensities at slower frequencies for the soleus and tibialis anterior and a decrease in mean amplitudes for the soleus, lateral gastrocnemius, and semitendinosus. Mean mediolateral CoM displacement following perturbations averaged 21% larger after the 30-min walk. Our results suggest that walking for 30 min at a comfortable speed elicits complex neuromuscular adaptations indicative of local muscle fatigue and an increased vulnerability to walking balance perturbations. These findings could inform fatigue monitoring systems or walking assistive devices aimed at reducing walking-related fatigue and maintaining independent mobility.

Mouse skeletal muscle adaptations to different durations of treadmill exercise after the cessation of FOLFOX chemotherapy.

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is a treatment for colorectal cancer that can induce persistent fatigue and metabolic dysfunction. Regular exercise after chemotherapy cessation is widely recommended for cancer patients and has been shown to improve fatigue resistance in mice. However, gaps remain in understanding whether the early systemic and skeletal muscle adaptations to regular exercise are altered by prior FOLFOX chemotherapy treatment. Furthermore, the effects of exercise duration on early metabolic and skeletal muscle transcriptional adaptations are not fully established. Purpose: Investigate the effects of prior FOLFOX chemotherapy treatment on the early adaptations to repeated short- or long-duration treadmill exercise, including the fasting regulation of circulating metabolic regulators, skeletal muscle COXIV activity and myokine/exerkine gene expression in male mice. Methods: Male C57BL6/J mice completed 4 cycles of FOLFOX or PBS and were allowed to recover for 4-weeks. Subsets of mice performed 14 sessions (6d/wk, 18m/min, 5% grade) of short- (10min/d) or long-duration (55min/d) treadmill exercise. Blood plasma and muscle tissues were collected 48-72h after the last exercise bout for biochemical analyses. Results: Long-duration exercise increased fasting plasma osteocalcin, LIF, and IL-6 in healthy PBS mice, and these changes were ablated by prior FOLFOX treatment. Slow-oxidative soleus muscle COXIV activity increased in response to long-duration exercise in PBS mice, which was blocked by prior FOLFOX treatment. Fast-glycolytic plantaris muscle COXIV activity increased with short-duration exercise independent of FOLFOX administration. There was a main effect for long-duration exercise to increase fasting muscle IL-6 and COXIV mRNA expression independent of FOLFOX. FOLFOX administration reduced muscle IL-6, LIF, and BDNF mRNA expression irrespective of long-duration exercise. Interestingly, short-duration exercise suppressed the FOLXOX induction of muscle myostatin mRNA expression. Conclusion: FOLFOX attenuated early exercise adaptations related to fasting circulating osteocalcin, LIF, and IL-6. However, prior FOLFOX treatment did not alter the exercise adaptations of plantaris muscle COXIV activity and plasma adiponectin. An improved understanding of mechanisms underlying exercise adaptations after chemotherapy will provide the basis for successfully treating fatigue and metabolic dysfunction in cancer survivors.

Crossroads of Nitric Oxide and Mitochondrial Metabolism: Implications for Skeletal Muscle Adaptations to Exercise

Crossroads of Nitric Oxide and Mitochondrial Metabolism: Implications for Skeletal Muscle Adaptations to Exercise

Cardiac and intramuscular adaptations following short-term exercise prehabilitation in unfit patients scheduled to undergo hepatic or pancreatic surgery: study protocol of a multinuclear MRI study

IntroductionShort-term exercise prehabilitation programmes have demonstrated promising results in improving aerobic capacity of unfit patients prior to major abdominal surgery. However, little is known about the cardiac and skeletal muscle...

Sex-Specific Effect of CARM1 in Skeletal Muscle Adaptations to Exercise.

The purpose of this study was to determine how the intersection of coactivator-associated arginine methyltransferase 1 (CARM1) and biological sex affects skeletal muscle adaptations to chronic physical activity. Twelve-week-old female (F) and male (M) wild-type (WT) and CARM1 skeletal muscle-specific knockout (mKO) mice were randomly assigned to sedentary (SED) or voluntary wheel running (VWR) experimental groups. For 8 wk, the animals in the VWR cohort had volitional access to running wheels. Subsequently, we performed whole-body functional tests, and 48 h later muscles were harvested for molecular analysis. Western blotting, enzyme activity assays, as well as confocal and transmission electron microscopy were used to examine skeletal muscle biology. Our data reveal a sex-dependent reduction in VWR volume caused by muscle-specific ablation of CARM1, as F CARM1 mKO mice performed less chronic, volitional exercise than their WT counterparts. Regardless of VWR output, exercise-induced adaptations in physiological function were similar between experimental groups. A broad panel of protein arginine methyltransferase (PRMT) biology measurements, including markers of arginine methyltransferase expression and activity, were unaffected by VWR, except for CARM1 and PRMT7 protein levels, which decreased and increased with VWR, respectively. Changes in myofiber morphology and mitochondrial protein content showed similar trends among animals. However, a closer examination of transmission electron microscopy images revealed contrasting responses to VWR in CARM1 mKO mice compared with WT littermates, particularly in mitochondrial size and fractional area. The present findings demonstrate that CARM1 mKO reduces daily running volume in F mice, as well as exercise-evoked skeletal muscle mitochondrial plasticity, which indicates that this enzyme plays an essential role in sex-dependent differences in exercise performance and mitochondrial health.

Inhibition of p53-MDM2 binding reduces senescent cell abundance and improves the adaptive responses of skeletal muscle from aged mice.

Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice. The goal of this study was to determine if a novel pharmaceutical agent (BI01), which functions by upregulating p53 through inhibition of binding to MDM2, the primary p53 regulatory protein, improves muscle regeneration and hypertrophy in old mice. BI01 effectively reduced the number of senescent cells in vitro but had no effect on MPC survival or proliferation at a comparable dose. Following repeated oral gavage with 2mg/kg of BI01 (OS) or vehicle (OV), old mice (24months) underwent unilateral BaCl2 injury in the tibialis anterior (TA) muscle, with PBS injections serving as controls. After 7days, satellite cell number was higher in the TA of OS compared to OV mice, as was the expression of genes involved in ATP production. By 35days, old mice treated with BI01 displayed reduced senescent cell burden, enhanced regeneration (higher muscle mass and fiber cross-sectional area) and restoration of muscle function relative to OV mice. To examine the impact of 2mg/kg BI01 on muscle hypertrophy, the plantaris muscle was subjected to 28days of mechanical overload (MOV) in OS and OV mice. In response to MOV, OS mice had larger plantaris muscles and muscle fibers than OV mice, particularly type 2b + x fibers, associated with reduced senescent cells. Together our data show that BI01 is an effective senolytic agent that may also augment muscle metabolism to enhance muscle regeneration and hypertrophy in old mice.

Transcriptome Analysis Revealed Potential Genes of Skeletal Muscle Thermogenesis in Mashen Pigs and Large White Pigs under Cold Stress.

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a four-day cold (4 °C) or normal temperature (25 °C) environment. We recorded phenotypic changes and collected blood and longissimus dorsi muscle for transcriptome sequencing. Finally, the PRSS8 gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency, were observed. However, the MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. The LW pigs primarily responded to cold stress by regulating their heat production and glycolipid energy metabolism. The MS pigs exhibited a distinct response to cold stress, involving the regulation of heat production, energy metabolism pathways, and robust mitochondrial activity, as well as a stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed that it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.

The Role of p53 in Skeletal Muscle Adaptation During Exercise: A Literature Review

Introduction: Due to its natural relationship with physiological health, skeletal muscle has been studied in a variety of contexts. Most commonly, it is analyzed during exercise to determine the adaptations caused by specific homeostatic imbalances. These imbalances pushed for more research in p53, a tumour suppressor known for regulating cellular stability. Methods: This literature review will be a narrative review using primary studies to determine the role of p53 in hypertrophy, mitochondrial biogenesis, and angiogenesis of skeletal muscles during exercise. Results: Differences in gene expression related to hypertrophy, mitochondrial biogenesis, and angiogenesis were observed during skeletal muscle adaptations dependent on p53 content and activity during and after exercise. Discussion: p53 content level was shown to contribute to skeletal muscle atrophy immediately following exercise, while having minimal effect on mitochondrial biogenesis. Rather, p53 activity was seen to be a more likely effector of mitochondrial levels. Moreover, through indirect pathways, p53 appears to negatively correlate with increases of angiogenesis in skeletal muscle. Conclusion: Research on p53 continues to express the importance of the protein beyond its role as a tumour suppressor. This review highlights alternative roles of p53 by analyzing its interactions in relation to exercise-induced adaptations of skeletal muscle.

Adaptability to eccentric exercise training is diminished with age in female mice.

The ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the fifth bout to identify common and differentially regulated genes. When torques post eccentric contractions were compared after the first and fifth bouts, young muscle exhibited a robust ability to adapt, increasing isometric torque 20%-36%, whereas isometric torque of older muscle decreased up to 18% (P ≤ 0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles.NEW & NOTEWORTHY The ability to adapt to exercise training may help prevent and combat sarcopenia. Here, we demonstrate young mouse muscles get stronger whereas older mouse muscles become weaker after repeated bouts of eccentric contractions, and that numerous genes were differentially expressed between age groups following training. These results highlight that molecular and functional plasticity is not fixed in skeletal muscle with advancing age, and the ability to handle or cope with physical stress may be impaired.

The effects of environmental enrichment on voluntary physical activity and muscle mass gain in growing rats.

Introduction: Environmental enrichment (EE) for rodents involves housing conditions that facilitate enhanced sensory, cognitive, and motor stimulation relative to standard housing conditions. A recent study suggested that EE induces muscle hypertrophy. However, it remains unclear whether muscle hypertrophy in EE is associated with voluntary physical activity, and the characteristics of muscle adaptation to EE remain unclarified. Therefore, this study investigated whether muscle adaptation to EE is associated with voluntary physical activity, and assessed the changes in the muscle fiber-type distribution and fiber-type-specific cross-sectional area in response to EE. Methods: Wistar rats (6weeks of age) were randomly assigned to either the standard environment group (n = 10) or the EE group (n = 10). The voluntary physical activity of rats housed in EE conditions was measured using a recently developed three-axis accelerometer. After exposure to the standard or enriched environment for 30days, the tibialis anterior, extensor digitorum longus, soleus, plantaris, and gastrocnemius muscles were removed and weighed. Immunohistochemistry analysis was performed on the surface (anterior) and deep (posterior) areas of the tibialis anterior and soleus muscles. Results and discussion: The EE group showed increased voluntary physical activity during the dark period compared with the standard environment group (p = 0.005). EE induced muscle mass gain in the soleus muscle (p = 0.002) and increased the slow-twitch muscle fiber cross-sectional area of the soleus muscle (p = 0.025). EE also increased the distribution of high-oxidative type IIa fibers of the surface area (p = 0.001) and type I fibers of the deep area (p = 0.037) of the tibialis anterior muscle. These findings suggest that EE is an effective approach to induce slow-twitch muscle fiber hypertrophy through increased daily voluntary physical activity.

Changes in the functional state of the skeletal muscles of badminton players during the formation of the mechanism of adaptation to motor activity

Objective. Determination of the nature of adaptation of skeletal muscles when performing special exercises in badminton.Materials and methods. The study involved 6 students, aged 18 - 20, of Gomel State Medical University practicing badminton. Testing of the functional state of skeletal muscles was carried out by myometrics method using myometer “MYOTON-3” and software “Myoton”.Results. The results of the study showed that the application of special exercises during 8-week microcycles promotes the formation of skeletal muscle adaptation to the performance of special competitive exercises of high intensity, expressed in the frequency of oscillation in a relaxed state in the range of 11-15 Hz. The processes of adaptation of muscular activity have an impact on improving the trajectory of the athlete’s body links, there is a decrease in the load on the articular joints of the upper limbs, expressed in terms of the muscle decrement index of at least 0.6 c.u., and the stiffness index of at least 0.45 N/m.Conclusions. Changes in the functional state of skeletal muscles as a result of a targeted impact contribute to an increase in strength potential, which leads to an increase in the performance of game activity.

RAD140 (Testolone) negatively impacts skeletal muscle adaptation, frailty status and mortality risk in female mice.

RAD140 is a selective androgen receptor modulator that produces anabolic effects within skeletal muscle. Thus, RAD140 may be effective at treating sarcopenia. No long-term studies have investigated how RAD140 influences strength in ageing muscle. This study aimed to determine how 10 weeks of RAD140 supplementation impacts strength, recovery from exercise, and overall health in ageing mice. Young and adult females were assigned to receive RAD140 (5 mg/kg) or a control solution. Dorsiflexor muscles were exposed to repeated bouts of eccentric contractions, and torque was measured before and after each bout. Adaptive potential and strength gains were calculated to assess the efficacy of RAD140 in muscle, while frailty status and mortality risk were used to measure health span. Supplementation of RAD140 increased frailty status and mortality risk in the young and adult treated groups compared to the controls (p ≤ 0.042). RAD140 decreased adaptive potential in young (p = 0.040) but not adult mice (p = 0.688). Torque did not differ between groups after 2-3 weeks of recovery (p ≥ 0.135). In conclusion, long-term RAD140 supplementation reduced indices of overall health and failed to improve strength in female mice, suggesting that RAD140 (at a 5mg/kg dosage) may be more detrimental than beneficial in delaying or preventing sarcopenia.

Hormonal, immune, and oxidative stress responses to blood flow-restricted exercise.

Heavy-load free-flow resistance exercise (HL-FFRE) is a widely used training modality. Recently, low-load blood-flow restricted resistance exercise (LL-BFRRE) has gained attention in both athletic and clinical settings as an alternative when conventional HL-FFRE is contraindicated or not tolerated. LL-BFRRE has been shown to result in physiological adaptations in muscle and connective tissue that are comparable to those induced by HL-FFRE. The underlying mechanisms remain unclear; however, evidence suggests that LL-BFRRE involves elevated metabolic stress compared to conventional free-flow resistance exercise (FFRE). The aim was to evaluate the initial (<10 min post-exercise), intermediate (10-20 min), and late (>30 min) hormonal, immune, and oxidative stress responses observed following acute sessions of LL-BFRRE compared to FFRE in healthy adults. A systematic literature search of randomized and non-randomized studies was conducted in PubMed, Embase, Cochrane Central, CINAHL, and SPORTDiscus. The Cochrane Risk of Bias (RoB2, ROBINS-1) and TESTEX were used to evaluate risk of bias and study quality. Data extractions were based on mean change within groups. A total of 12525 hits were identified, of which 29 articles were included. LL-BFRRE demonstrated greater acute increases in growth hormone responses when compared to overall FFRE at intermediate (SMD 2.04; 95% CI 0.87, 3.22) and late (SMD 2.64; 95% CI 1.13, 4.16) post-exercise phases. LL-BFRRE also demonstrated greater increase in testosterone responses compared to late LL-FFRE. These results indicate that LL-BFRRE can induce increased or similar hormone and immune responses compared to LL-FFRE and HL-FFRE along with attenuated oxidative stress responses compared to HL-FFRE.

Redox control of signalling responses to contractile activity and aging in skeletal muscle

During aging loss of skeletal muscle mass and function has a significant effect of an individual’s quality of life and ability to maintain independence. Both loss of muscle fibres and atrophy of the remaining fibres play a role in the muscle decline and this is associated with loss of motor units and a reduction in the number of motor neurons. Increased oxidative damage has long been claimed to be associated with aging and many studies have reported increased amounts of oxidative damage markers are found in tissues from old organisms. Reactive oxygen species (ROS) are recognised to play a major role in cell signalling and in muscle ROS generated during contractile play an important role in signalling adaptations to contractile activity. These ’redox-regulated’ pathways are beneficial adaptations which are attenuated during aging. This review will briefly cover what is currently known about the mechanisms underlying these muscle adaptations to exercise, how they are affected by aging and assess the importance of these pathways in age-related loss of skeletal muscle mass and function.

Skeletal muscle adaptations in patients with lung cancer: Longitudinal observations from the whole body to cellular level.

Cancer and its treatment can adversely affect skeletal muscle, impacting physical function, treatment response and survival. No studies, however, have comprehensively characterized these muscle adaptations longitudinally in human patients at the cellular level. We examined skeletal muscle size and function from the whole body to the sub-cellular level in 11 patients with non-small cell lung cancer (NSCLC; 6 male/5 female, mean age 58±3years) studied over a 2-month observation period starting during their first cycle of standard of care cancer treatment and in 11 age- and sex-matched healthy controls (HC) without a current or past history of cancer. Biopsies of the vastus lateralis were performed to assess muscle fibre size, contractility and mitochondrial content, along with assessments of physical function, whole muscle size and function, and circulating cytokines. Body weight, composition and thigh muscle area and density were unaltered over time in patients with NSCLC, while muscle density was lower in patients with NSCLC versus HC (P=0.03). Skeletal muscle fibre size decreased by 18% over time in patients (all P=0.02) and was lower than HC (P=0.02). Mitochondrial fractional area and density did not change over time in patients, but fractional area was lower in patients with NSCLC compared with HC (subsarcolemmal, P=0.04; intermyofibrillar, P=0.03). Patients with NSCLC had higher plasma concentrations of IL-6 (HC 1.40±0.50; NSCLC 4.71±4.22; P<0.01), GDF-15 (HC 569±166; NSCLC 2071±1168; P<0.01) and IL-8/CXCL8 (HC 4.9±1.8; NSCLC 10.1±6.0; P=0.02) compared with HC, but there were no changes in inflammatory markers in patients with NSCLC over time. No changes were observed in markers of satellite cell activation or DNA damage in patients and no group differences were noted with HC. Whole-muscle strength was preserved over time in patients with NSCLC coincident with improved single fibre contractility. This study is the first to comprehensively examine longitudinal alterations in skeletal muscle fibre size and function in patients with NSCLC and suggests that muscle fibre atrophy occurs during cancer treatment despite weight stability and no changes in conventional clinical measurements of whole body or thigh muscle size over this period.

Complex regulatory processes control exercise adaptations of skeletal muscle.

Complex regulatory processes control exercise adaptations of skeletal muscle.