Aged Skeletal Muscle Research Articles

Quality is more important than quantity: pre-operative sarcopenia is associated with poor survival in advanced ovarian cancer

BackgroundSarcopenia is prevalent among older patients with cancer and is associated with poor outcomes.ObjectiveTo explore the relationship between muscle mass, quality, and patient age with overall survival after surgery for...

Agastache rugosa Extract Combined With Voluntary Wheel Exercise Affects the Improvement of Skeletal Muscle Homeostasis in Aged C57BL/6J Mice

ObjectivesThis study aimed to investigate the beneficial effects of Agastache rugosa (AR) combined with wheel running exercise on maintaining muscle homeostasis in aged skeletal muscle.MethodsMale 38-week-old C57BL/6J mice were divided into five groups (n = 8/group): control (CON), Low-dose AR-treated (ARL, 100 mg/kg/day), High-dose AR-treated (ARH, 200 mg/kg/day), exercise (EXC), and EXC + ARH (EXH) group. After 2 weeks of acclimation period, AR-treated groups were fed AR extract by oral administration for 4 weeks. The daily voluntary wheel running (VWR) distance was recorded using a counter machine. In the gastrocnemius (GAS) muscle sample, muscle homeostasis-related genes and protein were analyzed by qPCR and western blotting, respectively.ResultsThe weight of GAS in ARH and EXH increased significantly, compared to CON (p < 0.05). qPCR analysis showed that AR and exercise affected both oxidative and glycolytic muscle fibers. mRNA levels of Myh7 and Myh1 in EXH were remarkably higher than in CON (p < 0.05). Skeletal muscle atrophy (Atrogin-1 and MuRF-1) and hypertrophy (myogenin) related genes were up-regulated in EXC compared to CON (p < 0.05). Meanwhile, EXH dramatically down-regulated Atrogin-1 and MuRF-1 and up-regulated <> (p < 0.05). Western blotting analysis indicated that the hypertrophy-related protein p70S6 showed high levels in both exercise groups, but there was no statistically significant difference. In contrast, atrophy-related protein FOXO3a and MuRF-1 levels were remarkably lower in the EXC and EXH (p < 0.05).ConclusionsTaken together, this study demonstrated that AR with VWR exercise enhanced muscle homeostasis via regulation of skeletal muscle protein synthesis and degradation markers in aged hind-limb muscles. In conclusion, AR could be a promising candidate for maintaining muscle homeostasis and further alleviating sarcopenia.Funding SourcesThis work was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (2012M3A9C4048761).

Taurine Administration Counteracts Aging-Associated Impingement of Skeletal Muscle Regeneration by Reducing Inflammation and Oxidative Stress.

Sarcopenia, which occurs during aging, is characterized by the gradual loss of skeletal muscle mass and function, resulting in a functional decline in physical abilities. Several factors contribute to the onset of sarcopenia, including reduced regenerative capacity, chronic low-grade inflammation, mitochondrial dysfunction, and increased oxidative stress, leading to the activation of catabolic pathways. Physical activity and adequate protein intake are considered effective strategies able to reduce the incidence and severity of sarcopenia by exerting beneficial effects in improving the muscular anabolic response during aging. Taurine is a non-essential amino acid that is highly expressed in mammalian tissues and, particularly, in skeletal muscle where it is involved in the regulation of biological processes and where it acts as an antioxidant and anti-inflammatory factor. Here, we evaluated whether taurine administration in old mice counteracts the physiopathological effects of aging in skeletal muscle. We showed that, in injured muscle, taurine enhances the regenerative process by downregulating the inflammatory response and preserving muscle fiber integrity. Moreover, taurine attenuates ROS production in aged muscles by maintaining a proper cellular redox balance, acting as an antioxidant molecule. Although further studies are needed to better elucidate the molecular mechanisms responsible for the beneficial effect of taurine on skeletal muscle homeostasis, these data demonstrate that taurine administration ameliorates the microenvironment allowing an efficient regenerative process and attenuation of the catabolic pathways related to the onset of sarcopenia.

CYB5R3 overexpression preserves skeletal muscle mitochondria and autophagic signaling in aged transgenic mice

Cytochrome b5 reductase 3 (CYB5R3) overexpression activates respiratory metabolism and exerts prolongevity effects in transgenic mice, mimicking some of the salutary effects of calorie restriction. The aim of our study was to understand how CYB5R3 overexpression targets key pathways that modulate the rate of aging in skeletal muscle, a postmitotic tissue with a greater contribution to resting energy expenditure. Mitochondrial function, autophagy and mitophagy markers were evaluated in mouse hind limb skeletal muscles from young-adult (7 months old) and old (24 months old) males of wild-type and CYB5R3-overexpressing genotypes. Ultrastructure of subsarcolemmal and intermyofibrillar mitochondria was studied by electron microscopy in red gastrocnemius. CYB5R3, which was efficiently overexpressed and targeted to skeletal muscle mitochondria regardless of age, increased the abundance of complexes I, II, and IV in old mice and prevented the age-related decrease of complexes I, III, IV, and V and the mitofusin MFN-2. ATP was significantly decreased by aging, which was prevented by CYB5R3 overexpression. Coenzyme Q and the mitochondrial biogenesis markers TFAM and NRF-1 were also significantly diminished by aging, but CYB5R3 overexpression did not protect against these declines. Both aging and CYB5R3 overexpression upregulated SIRT3 and the mitochondrial fission markers FIS1 and DRP-1, although with different outcomes on mitochondrial ultrastructure: old wild-type mice exhibited mitochondrial fragmentation whereas CYB5R3 overexpression increased mitochondrial size in old transgenic mice concomitant with an improvement of autophagic recycling. Interventions aimed at stimulating CYB5R3 could represent a valuable strategy to counteract the deleterious effects of aging in skeletal muscle.Graphical abstract

Neuromuscular Synapse Dynamics in Aged and Injured Skeletal Muscle

It is evident that both aged and diseased skeletal muscle exhibit interesting neuromuscular dynamics, characterized by changes in morphology and functionality of the synapse. Although they display a high regenerative capacity, skeletal muscles are still susceptible to nervous system perturbations and impacts of aging. Aged neuromuscular junctions (NMJs) demonstrate a diseased phenotype following some form of muscle atrophy, indicating the presence of paracrine signaling between myofibers and neuronal cells. In this study, we investigated differences in neuromuscular dynamics in injured and aged skeletal muscle using whole‐mount immunostaining and imaging. It has previously been shown that disruption of one component of the muscle microenvironment, such as vasculature, disrupts the structure of NMJs, however it is unclear if aged skeletal muscle experiences similar changes. We hypothesized that both aged and injured NMJs would display similar morphological dynamics, characterized by denervation and fragmentation of postsynaptic acetylcholine receptors (AChRs). We demonstrated that aged and injured NMJs exhibit fragmentation of AChRs, Wallerian degeneration of the presynaptic motor neurons, decreased overlap of pre‐ and post‐synaptic sides, and decreased area of AChR clusters. Due to the prevalence of neuromuscular disorders in the aging population, it is pertinent to understand nerve‐muscle interactions in the healthy aging state in order to hypothesize how these dynamics may be altered in the age‐induced injury states. Ultimately, this will allow us to better comprehend the molecular and cellular mechanisms that are responsible for neuromuscular degeneration in order to develop strategies to improve mobility and quality of life.

Mitochondrial calcium retention capacity correlates with markers of muscle mass, strength, power and functional capacities in young and old adults

RationaleThe aging‐related loss of muscle mass and function is a major risk factor for falls, fractures, frailty, loss of independence, institutionalization and even death. Although the underlying cellular and molecular mechanisms remain partly understood, impaired mitochondrial permeability transition pore (mPTP) function has been proposed as a potential mechanism. Indeed, altered mitochondrial calcium retention capacity (mCRC), a marker of mPTP function, has been documented with aging in both rodent and human skeletal muscles and mPTP opening was shown to cause muscle atrophy. However, studies on the impact of aging on mPTP function in humans remain scarce, and whether impaired mPTP function correlates with markers of muscle mass, performance and functional capacities remain unknown.ObjectiveThe present study aimed at investigating whether mCRC is associated with markers of muscle mass, muscle function and functional capacities in humans.MethodsTwelve young (29.4 ± 4.4y) and fourteen old (80 ± 7.4y) healthy men were enrolled in the present study. Leg lean mass (leg LM) was assessed using DEXA. Maximal isometric knee extension strength (iKES) and power were measured using a strain gauge system attached to a chair and the Nottingham Leg Extensor Power rig, respectively. To assess functional capacities, the performance at the 6‐min walk test and the step test (maximum number of steps in 20s) were evaluated. To assess mPTP function, mCRC was measured in permeabilized myofibers prepared from muscle biopsies obtained in the vastus lateralis.ResultsAs compared to young adults, old individuals displayed significantly lower leg LM (p&lt;0.01), iKES (p&lt;0.01), and power (p&lt;0.01). The performance at the 6‐min walk test (p&lt;0.01) and the step test (p&lt;0.01) were also lower in old individuals. Old individuals also displayed a significantly lower mCRC (p&lt;0.01). mCRC was significantly correlated with leg LM (r=0.34; p=0.045), iKES (r=0.35; p=0.04) and muscle power (r=0.41; p=0.02). In addition, mCRC was significantly correlated with the performance at the 6‐min walking test (r=0.42;p=0.01) and step test (r=0.46; p&lt;0.01).ConclusionsThese results indicate that mPTP function is altered with aging in humans and highlight positive associations between mPTP, muscle mass, strength, power, and functional capacities. These findings therefore strengthen the emerging view that altered mPTP function contributes to the aging‐related loss of muscle mass and function in humans.

Effect of 32-Weeks High-Intensity Interval Training and Resistance Training on Delaying Sarcopenia: Focus on Endogenous Apoptosis.

Sarcopenia caused by aging is an important factor leading to a decline in the quality of life of older people. Apoptosis in muscle atrophy accelerates the process of muscle loss in older populations. The present study aimed to investigate the effects of 32 weeks of high-intensity interval training (HIIT) and resistance training (RT) on the skeletal muscle-related indices and provide a theoretical basis for regulating the mitochondrial-mediated pathway to delay sarcopenia. We randomly selected 10 from eight-month-old male SD rats (N = 130) as the baseline group; after 1 week of adaptive feeding, the rats were sacrificed. The remaining rats were randomly assigned to one of three groups: control group (C, N = 40, natural aging for 32 weeks), HIIT group (H, N = 40, performed six loops of 3 min at 90% and 3 min at 50% VO2 max speed treadmill running, with 5 min at 70% VO2 max speed at the beginning and the end of the training, 3 times a week for 32 weeks), and resistance group (R, n = 40, 46 min per day, 3 days per week, with a 30% maximum load on a treadmill with a slope of 35°, 15 m/min). The soleus muscles were collected for analysis at baseline and every 8 weeks. Aging resulted in decreased soleus muscle mass and Bcl-2 levels in the mitochondria, while the levels of reactive oxygen species (ROS) and Bax did not change. HIIT reversed the age-associated activation of pro-apoptotic processes, but RT did not. In addition, when rats were aged from 8 to 16 months, the level of Cyt-C did not change, the Caspase-9 levels and Caspase-3 levels decreased gradually in the soleus muscles, the rats of both the HIIT and RT groups had these indices decreased at 32 weeks. The results suggest that the age-associated loss of muscle mass was reversed by training, and the effect of RT was better than that of HIIT. Both the HIIT and RT rats showed a decrease in the apoptosis of skeletal muscle cells after 32 weeks of intervention. HIIT performed better for long-term intervention regarding the pro-apoptotic factors. This study warranted further research to delineate the underlying mechanism of effects of different exercise methods on the changes of aging skeletal muscle at in vivo level.

Characterization of the Skeletal Muscle Proteome in Undernourished Old Rats.

Aging is associated with a progressive loss of skeletal muscle mass and function termed sarcopenia. Various metabolic alterations that occur with aging also increase the risk of undernutrition, which can worsen age-related sarcopenia. However, the impact of undernutrition on aged skeletal muscle remains largely under-researched. To build a deeper understanding of the cellular and molecular mechanisms underlying age-related sarcopenia, we characterized the undernutrition-induced changes in the skeletal muscle proteome in old rats. For this study, 20-month-old male rats were fed 50% or 100% of their spontaneous intake for 12 weeks, and proteomic analysis was performed on both slow- and fast-twitch muscles. Proteomic profiling of undernourished aged skeletal muscle revealed that undernutrition has profound effects on muscle proteome independently of its effect on muscle mass. Undernutrition-induced changes in muscle proteome appear to be muscle-type-specific: slow-twitch muscle showed a broad pattern of differential expression in proteins important for energy metabolism, whereas fast-twitch muscle mainly showed changes in protein turnover between undernourished and control rats. This first proteomic analysis of undernourished aged skeletal muscle provides new molecular-level insight to explain phenotypic changes in undernourished aged muscle. We anticipate this work as a starting point to define new biomarkers associated with undernutrition-induced muscle loss in the elderly.

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making “CR mimetics” of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Here we show that long-term CR and rapamycin unexpectedly display distinct gene expression profiles in geriatric mouse skeletal muscle, despite both benefiting aging muscles. Furthermore, CR improves muscle integrity in mice with nutrient-insensitive, sustained muscle mTORC1 activity and rapamycin provides additive benefits to CR in naturally aging mouse muscles. We conclude that rapamycin and CR exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging.

Development of a cell-free strategy to recover aged skeletal muscle after disuse.

Extended periods of bed rest and limb immobilization are required for healing post-injury or disease, yet disuse can result in significant muscle atrophy and decreased quality of life in older adults. Physical rehabilitation is commonly prescribed to recover these deficits, yet accumulation of reactive oxygen species and sustained rates of protein degradation persist during the rehabilitation period that can significantly delay or prevent recovery. Pericytes, considered the primary mesenchymal and vascular stromal cell in skeletal muscle, secrete beneficial factors that maintain baseline muscle mass, yet minimal information exists regarding the pericyte response to disuse and recovery. In the current study, single-cell RNA sequencing and functional assays were performed to demonstrate that pericytes in mouse skeletal muscle lose the capacity to synthesize antioxidants during disuse and recovery. This information was used to guide the design of a strategy in which healthy donor pericytes were stimulated with hydrogen peroxide (H2 O2 ) to produce small extracellular vesicles (sEVs) that effectively restored myofibre size in adult and aged muscle after disuse. Proteomic assessment detected 11 differentially regulated proteins in primed sEVs that may account for recovery of muscle, including proteins associated with extracellular matrix composition and anti-inflammatory and antioxidant processes. This study demonstrates that healthy H2 O2 -primed pericyte-derived sEVs effectively improve skeletal muscle recovery after immobilization, presenting a novel acellular approach to rebuild muscle mass in older adults after a period of disuse. KEY POINTS: Previous studies suggest that prolonged oxidative stress is a barrier to skeletal muscle recovery after a period of immobilization. In this study we demonstrate that muscle-resident perivascular stromal cells (pericytes) become dysfunctional and lack the capacity to mount an antioxidant defence after disuse in mice. Hydrogen peroxide treatment of healthy pericytes in vitro simulates the release of small extracellular vesicles (sEVs) that effectively recover skeletal muscle fibre size and extracellular matrix remodelling in young adult and aged mice after disuse. Pericyte-derived sEVs present a novel acellular strategy to recover skeletal muscle after disuse.

Therapeutic effects of recreational exercise on skeletal muscle ageing - how much is enough?

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NAD+ centric mechanisms and molecular determinants of skeletal muscle disease and aging.

The nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor, involved in various physiological and molecular processes, including energy metabolism, epigenetics, aging, and metabolic diseases. NAD+ repletion ameliorates muscular dystrophy and improves the mitochondrial and muscle stem cell function and thereby increase lifespan in mice. Accordingly, NAD+ is considered as an anti-oxidant and anti-aging molecule. NAD+ plays a central role in energy metabolismand the energy produced is used for movements, thermoregulation, and defense against foreign bodies.The dietary precursors of NAD+ synthesis is targeted to improve NAD+ biosynthesis; however, studies have revealed conflicting results regarding skeletal muscle-specific effects. Recent advances in the activation ofnicotinamide phosphoribosyltransferase in the NAD+ salvage pathway and supplementation of NAD+ precursors have led to beneficial effects in skeletal muscle pathophysiology and function during aging and associated metabolic diseases. NAD+ is also involved in the epigenetic regulation and post-translational modifications of proteins that are involved in various cellular processes to maintain tissue homeostasis. This review provides detailed insights into the roles of NAD+ along with molecular mechanisms during aging and disease conditions, such as the impacts of age-related NAD+ deficiencies on NAD+-dependent enzymes, including poly (ADP-ribose) polymerase (PARPs), CD38, and sirtuins within skeletal muscle, and the most recent studies on the potential of nutritional supplementation and distinct modes of exercise to replenish the NAD+ pool.

The Role of MicroRNAs in Proteostasis Decline and Protein Aggregation during Brain and Skeletal Muscle Aging.

Aging can be defined as the progressive deterioration of cellular, tissue, and organismal function over time. Alterations in protein homeostasis, also known as proteostasis, are a hallmark of aging that lead to proteome imbalances and protein aggregation, phenomena that also occur in age-related diseases. Among the various proteostasis regulators, microRNAs (miRNAs) have been reported to play important roles in the post-transcriptional control of genes involved in maintaining proteostasis during the lifespan in several organismal tissues. In this review, we consolidate recently published reports that demonstrate how miRNAs regulate fundamental proteostasis-related processes relevant to tissue aging, with emphasis on the two most studied tissues, brain tissue and skeletal muscle. We also explore an emerging perspective on the role of miRNA regulatory networks in age-related protein aggregation, a known hallmark of aging and age-related diseases, to elucidate potential miRNA candidates for anti-aging diagnostic and therapeutic targets.

Preserved stem cell content and innervation profile of elderly human skeletal muscle with lifelong recreational exercise

Muscle fibre denervation and declining numbers of muscle stem (satellite) cells are defining characteristics of ageing skeletal muscle. The aim of this study was to investigate the potential for lifelong recreational exercise to offset muscle fibre denervation and compromised satellite cell content and function, both at rest and under challenged conditions. Sixteen elderly lifelong recreational exercisers (LLEX) were studied alongside groups of age‐matched sedentary (SED) and young subjects. Lean body mass and maximal voluntary contraction were assessed, and a strength training bout was performed. From muscle biopsies, tissue and primary myogenic cell cultures were analysed by immunofluorescence and RT‐qPCR to assess myofibre denervation and satellite cell quantity and function. LLEX demonstrated superior muscle function under challenged conditions. When compared with SED, the muscle of LLEX was found to contain a greater content of satellite cells associated with type II myofibres specifically, along with higher mRNA levels of the beta and gamma acetylcholine receptors (AChR). No difference was observed between LLEX and SED for the proportion of denervated fibres or satellite cell function, as assessed in vitro by myogenic cell differentiation and fusion index assays. When compared with inactive counterparts, the skeletal muscle of lifelong exercisers is characterised by greater fatigue resistance under challenged conditions in vivo, together with a more youthful tissue satellite cell and AChR profile. Our data suggest a little recreational level exercise goes a long way in protecting against the emergence of classic phenotypic traits associated with the aged muscle.Key points The detrimental effects of ageing can be partially offset by lifelong self‐organized recreational exercise, as evidence by preserved type II myofibre‐associated satellite cells, a beneficial muscle innervation status and greater fatigue resistance under challenged conditions.Satellite cell function (in vitro), muscle fibre size and muscle fibre denervation determined by immunofluorescence were not affected by recreational exercise.Individuals that are recreationally active are far more abundant than master athletes, which sharply increases the translational perspective of the present study. Future studies should further investigate recreational activity in relation to muscle health, while also including female participants.

Exercise-mediated reinnervation of skeletal muscle in elderly people: An update.

Sarcopenia is defined by the loss of muscle mass and function. In aging sarcopenia is due to mild chronic inflammation but also to fiber-intrinsic defects, such as mitochondrial dysfunction. Age-related sarcopenia is associated with physical disability and lowered quality of life. In addition to skeletal muscle, the nervous tissue is also affected in elderly people. With aging, type 2 fast fibers preferentially undergo denervation and are reinnervated by slow-twitch motor neurons. They spread forming new neuro-muscular junctions with the denervated fibers: the result is an increased proportion of slow fibers that group together since they are associated in the same motor unit. Grouping and fiber type shifting are indeed major histological features of aging skeletal muscle. Exercise has been proposed as an intervention for age-related sarcopenia due to its numerous beneficial effects on muscle mechanical and biochemical features. In 2013, a precursor study in humans was published in the European Journal of Translation Myology (formerly known as Basic and Applied Myology), highlighting the occurrence of reinnervation in the musculature of aged, exercise-trained individuals as compared to the matching control. This paper, entitled «Reinnervation of Vastus lateralis is increased significantly in seniors (70-years old) with a lifelong history of high-level exercise», is now being reprinted for the second issue of the «Ejtm Seminal Paper Series». In this short review we discuss those results in the light of the most recent advances confirming the occurrence of exercise-mediated reinnervation, ultimately preserving muscle structure and function in elderly people who exercise.

Non-coding RNAs-associated ceRNA networks involved in the amelioration of skeletal muscle aging after whey protein supplementation

Whey protein has been reported to be an impactful dietary supplement to ameliorate skeletal muscle aging for a long time. However, whether whey protein could contribute to muscle aging amelioration by post-transcriptional modulation remains unclear. In this study, 19-month-old mice orally received whey protein supplementation (1.0 g/kg/bw/d, whey protein group) or deionized water (the control group) for 3 months. Differentially expressed ncRNAs and mRNAs in quadriceps were identified by RNA-seq. Construction of non-coding RNAs (ncRNAs)-associated competing endogenous RNA (ceRNA) networks as well as GO and KEGG enrichment analyses were also carried out subsequently. Meanwhile, ultrasound measurement, H&E staining, myofiber cross-sectional area measurement, western blotting and RT-qPCR were performed in the quadriceps to evaluate muscle status and verify the RNA-seq data. Whey protein supplementation for 3 months increased quadriceps-body weight ratio and improved the histological as well as ultrasonographic characteristics of aging in muscle. Moreover, the protein expression levels of Myog, Myf4, Myf5 and MyoD1 were all significantly elevated in quadriceps. The expression of 90 lncRNAs, 334 mRNAs, six circRNAs and 52 miRNAs were significantly up or down-regulated in quadriceps after whey protein supplementation. Furthermore, ncRNAs-associated networks and GO and KEGG enrichment analyses revealed whey protein may influence muscle aging process through selected ncRNAs-associated ceRNA networks. Therefore, post-transcriptional modulation could be a potential crucial way to ameliorate skeletal muscle aging after whey protein supplementation. The selected ncRNAs-associated ceRNA networks may provide new insight for the underlying mechanism and profound therapeutic target for skeletal muscle aging.

Muscle aging amelioration by yeast protein supplementation was associated with gut microbiota

• Yeast protein improved muscle histologically and ultrasonically and increased myofiber size. • Yeast protein promoted muscle protein synthesis and muscle regeneration and differentiation. • The composition and diversities of gut microbiota were altered by yeast protein. • Yeast protein-induced gut microbiota changes were closely involved in the process of muscle aging. There may be close links among yeast protein (Saccharomyces cerevisiae) supplementation, gut microbiota and skeletal muscle aging. In present study, nineteen-month-old mice received yeast protein (1.0 g/kg/d) for three months by gavage. Histological and ultrasonographical improvements in muscle as well as an increase in myofiber size were observed after yeast protein supplementation. Moreover, yeast protein activated Akt/mTOR/4E-BP1 pathway and regulated myogenic regulatory factors (Myog, Myf4, Myf5, and Myod1) to promote muscle protein synthesis and muscle regeneration and differentiation. Meanwhile, alpha and beta diversities as well as the ratio of Firmicutes and Bacteroidetes were elevated after yeast protein supplementation. Changes in the abundance of gut microbiota after yeast protein supplementation were significantly correlated with glycan biosynthesis and metabolism, amino acid metabolism and lipid metabolism, closely involved in the process of muscle aging. Hence, yeast protein supplementation could contribute to ameliorating muscle aging, which may be associated with gut microbiota.

Sex-Specific Associations Between Bone-Loading Score and Adiposity Markers in Middle-Aged and Older Adults.

The authors examined sex-specific relationships between fat mass index (FMI), android/gynoid (A/G) fat ratio, relative skeletal muscle mass index, and Bone-Specific Physical Activity Questionnaire derived bone-loading scores (BLSs) in middle-aged and older adults (men, n = 27; women, n = 33; age = 55-75years). The FMI, A/G fat ratio, and relative skeletal muscle mass index were estimated by dual-energy X-ray absorptiometry. The Bone-Specific Physical Activity Questionnaire was used to assess: (a)BLSpast (age 1 until 12months before the study visit), (b)BLScurrent (last 12months), and (c)BLStotal (average of [a] and [b]) scores. Separate multiple linear regression analysis of (a)age, FMI, and relative skeletal muscle mass index and (b)age, height, and A/G fat ratio versus BLS revealed that FMI and A/G fat ratio were negatively associated with BLSpast and BLStotal (p < .05) in women only. Adiposity and, specifically, central adiposity is negatively related to bone-loading physical activity in middle-aged and older women.

Decline of regenerative potential of old muscle stem cells: contribution to muscle aging.

Muscle stem cells (MuSCs) are required for life-long muscle regeneration. In general, aging has been linked to a decline in the numbers and the regenerative potential of MuSCs. Muscle regeneration depends on the proper functioning of MuSCs, which is itself dependent on intricate interactions with its niche components. Aging is associated with both cell-intrinsic and niche-mediated changes, which can be the result of transcriptional, posttranscriptional, or posttranslational alterations in MuSCs or in the components of their niche. The interplay between cell intrinsic alterations in MuSCs and changes in the stem cell niche environment during aging and its impact on the number and the function of MuSCs is an important emerging area of research. In this review, we discuss whether the decline in the regenerative potential of MuSCs with age is the cause or the consequence of aging skeletal muscle. Understanding the effect of aging on MuSCs and the individual components of their niche is critical to develop effective therapeutic approaches to diminish or reverse the age-related defects in muscle regeneration.

Long Non-coding RNA MALAT1 Is Depleted With Age in Skeletal Muscle in vivo and MALAT1 Silencing Increases Expression of TGF-β1 in vitro

Long non-coding RNAs (lncRNAs) are thought to function as “sponges” for microRNAs, but a role for such competing endogenous RNAs (ceRNAs) in muscle aging is not well understood. We therefore examined in skeletal muscles of young (4–6 months) and aged (22–24) male and female mice the expression of lncRNA MALAT1, which is predicted in silico to bind the senescence-associated microRNA miR-34a-5p. Results indicate a significant decrease in lncRNA MALAT1 expression in mouse skeletal muscle with age that coincides with an age-related increase in miR-34a-5p expression. In vitro studies using mouse C2C12 myoblasts demonstrate that MALAT1 silencing using siRNA increases miR-34a expression, consistent with a role for MALAT1 as an inhibitor of miR-34a-5p activity. Levels of reactive oxygen species (ROS) are known to increase in muscle with age, and so we treated C2C12 cells with hydrogen peroxide (10 and 100 μM) to examine changes in MALAT1 expression. MALAT1 expression decreased significantly with H2O2 treatment, but this effect was attenuated with p53 siRNA. Finally, miR-34a-5p is implicated in tissue fibrosis, and so we assessed the expression of TGF-β1 after MALAT1 silencing. MALAT1 siRNA significantly increased the expression of TGF-β1 in C2C12 cells. These findings suggest that age-related fibrosis and muscle atrophy mediated by ROS may result at least in part from an increase in miR-34a bioavailability resulting from a decline in miR-34a “sponging” due to ceRNA MALAT1 depletion. Crosstalk between MALAT1 and miR-34a may therefore represent a therapeutic target for improving muscle function with aging.