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The American Journal of Clinical... Nov 2023Sarcopenia is a common skeletal muscle disorder characterized by a loss of muscle mass and impaired muscle function that is associated with poor health outcomes.... (Review)
Review
Sarcopenia is a common skeletal muscle disorder characterized by a loss of muscle mass and impaired muscle function that is associated with poor health outcomes. Although nutrition is considered an important factor in the etiology of sarcopenia, the preventive potential of diet, specifically the extent to which differences in habitual patterns of diet and/or nutrient intakes impact risk of its development, is poorly understood. This narrative review considered research evidence on dietary patterns and nutrient intakes in mid- (<60 y) and young-older (60-70 y) adulthood to evaluate how they relate to age-related changes in muscle mass and function. A key finding was that current evidence on adult diet and sarcopenia risk in older age is limited and fragmented, with different outcomes reported across studies (for example, lean mass, strength) and few reporting links to incident diagnosed sarcopenia. As these outcomes are not interchangeable, it challenges collation of the evidence, leaving many gaps in understanding. There is also limited information about adult (<70 y) diet and few longitudinal studies with repeated dietary assessments to enable definition of cumulative exposures across adulthood. However, despite these limitations, findings from studies of dietary patterns already provide reasonably consistent messages about the benefits of diets of higher quality in earlier adulthood for later physical performance, although whole-diet intervention trials are urgently needed to understand their potential. In comparison, there is little evidence of benefits of higher intakes of individual nutrients in earlier adulthood for later muscle mass and function. Although these gaps need to be addressed in future research, there may already be sufficient data to promote messages about diet quality more widely - that healthier diets of higher quality across adulthood, with known benefits for a range of health outcomes, are also linked to the effective preservation of muscle mass and function.
Topics: Adult; Humans; Sarcopenia; Muscle Strength; Muscle, Skeletal; Nutritional Status; Diet
PubMed: 37657521
DOI: 10.1016/j.ajcnut.2023.08.015 -
Endocrine Reviews Jul 2023Mitochondria sense both biochemical and energetic input in addition to communicating signals regarding the energetic state of the cell. Increasingly, these signaling... (Review)
Review
Mitochondria sense both biochemical and energetic input in addition to communicating signals regarding the energetic state of the cell. Increasingly, these signaling organelles are recognized as key for regulating different cell functions. This review summarizes recent advances in mitochondrial communication in striated muscle, with specific focus on the processes by which mitochondria communicate with each other, other organelles, and across distant organ systems. Intermitochondrial communication in striated muscle is mediated via conduction of the mitochondrial membrane potential to adjacent mitochondria, physical interactions, mitochondrial fusion or fission, and via nanotunnels, allowing for the exchange of proteins, mitochondrial DNA, nucleotides, and peptides. Within striated muscle cells, mitochondria-organelle communication can modulate overall cell function. The various mechanisms by which mitochondria communicate mitochondrial fitness to the rest of the body suggest that extracellular mitochondrial signaling is key during health and disease. Whereas mitochondria-derived vesicles might excrete mitochondria-derived endocrine compounds, stimulation of mitochondrial stress can lead to the release of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) into the circulation to modulate whole-body physiology. Circulating mitochondrial DNA are well-known alarmins that trigger the immune system and may help to explain low-grade inflammation in various chronic diseases. Impaired mitochondrial function and communication are central in common heart and skeletal muscle pathologies, including cardiomyopathies, insulin resistance, and sarcopenia. Lastly, important new advances in research in mitochondrial endocrinology, communication, medical horizons, and translational aspects are discussed.
Topics: Humans; Mitochondria; Muscle, Skeletal
PubMed: 36725366
DOI: 10.1210/endrev/bnad004 -
Nucleic Acids Research Jul 2023Although targeting TfR1 to deliver oligonucleotides to skeletal muscle has been demonstrated in rodents, effectiveness and pharmacokinetic/pharmacodynamic (PKPD)...
Although targeting TfR1 to deliver oligonucleotides to skeletal muscle has been demonstrated in rodents, effectiveness and pharmacokinetic/pharmacodynamic (PKPD) properties remained unknown in higher species. We developed antibody-oligonucleotide conjugates (AOCs) towards mice or monkeys utilizing anti-TfR1 monoclonal antibodies (αTfR1) conjugated to various classes of oligonucleotides (siRNA, ASOs and PMOs). αTfR1 AOCs delivered oligonucleotides to muscle tissue in both species. In mice, αTfR1 AOCs achieved a > 15-fold higher concentration to muscle tissue than unconjugated siRNA. A single dose of an αTfR1 conjugated to an siRNA against Ssb mRNA produced > 75% Ssb mRNA reduction in mice and monkeys, and mRNA silencing was greatest in skeletal and cardiac (striated) muscle with minimal to no activity in other major organs. In mice the EC50 for Ssb mRNA reduction in skeletal muscle was >75-fold less than in systemic tissues. Oligonucleotides conjugated to control antibodies or cholesterol produced no mRNA reduction or were 10-fold less potent, respectively. Tissue PKPD of AOCs demonstrated mRNA silencing activity primarily driven by receptor-mediated delivery in striated muscle for siRNA oligonucleotides. In mice, we show that AOC-mediated delivery is operable across various oligonucleotide modalities. AOC PKPD properties translated to higher species, providing promise for a new class of oligonucleotide therapeutics.
Topics: Mice; Animals; Oligonucleotides; Oligonucleotides, Antisense; Antibodies; RNA, Small Interfering; RNA, Messenger; Muscle, Skeletal
PubMed: 37224533
DOI: 10.1093/nar/gkad415 -
Annals of Medicine Dec 2023Technological advances of hand-held ultrasound devices and educational programmes for their use, such as point-of-care ultrasonography (POCUS) training, have contributed... (Review)
Review
Technological advances of hand-held ultrasound devices and educational programmes for their use, such as point-of-care ultrasonography (POCUS) training, have contributed to the increasing application of these devices in clinical practice. With the greater impact of frailty and sarcopenia in aging societies, attention is being focused on the use of ultrasound for skeletal muscle assessment. In this narrative review, we discuss how ultrasound can be applied to skeletal muscle assessment, especially that of the quadriceps muscle, in clinical practice. Muscle thickness by ultrasound has been shown to have good reliability and validity for the evaluation of muscle size, and echo intensity has been used to evaluate muscle quality. Muscle ultrasound has not only been useful to diagnose sarcopenia in various settings, but has also been validated to predict health-related outcomes such as death and functional disability. Recommended methods for muscle ultrasound was published recently, and the results of future studies are expected to be comparable. Although several challenging issues with muscle ultrasound remain, if it could be incorporated into educational programmes such as POCUS training, more clinicians may be able to use ultrasound for skeletal muscle assessment in the future.KEY MESSAGESThe evolution of hand-held ultrasound devices enables physicians to perform ultrasound at the bedside as part of regular medical examinations.Muscle ultrasound is considered an effective tool for evaluating muscle size and quality, and has been studied in various settings.More clinicians may be able to evaluate skeletal muscle assessment with the development of educational programmes on muscle ultrasound in the future.
Topics: Humans; Sarcopenia; Point-of-Care Systems; Reproducibility of Results; Muscle, Skeletal; Ultrasonography
PubMed: 36538042
DOI: 10.1080/07853890.2022.2157871 -
Journal of Sport and Health Science Jan 2024The aim of this umbrella review was to determine the impact of resistance training (RT) and individual RT prescription variables on muscle mass, strength, and physical... (Review)
Review
PURPOSE
The aim of this umbrella review was to determine the impact of resistance training (RT) and individual RT prescription variables on muscle mass, strength, and physical function in healthy adults.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched and screened eligible systematic reviews reporting the effects of differing RT prescription variables on muscle mass (or its proxies), strength, and/or physical function in healthy adults aged >18 years.
RESULTS
We identified 44 systematic reviews that met our inclusion criteria. The methodological quality of these reviews was assessed using A Measurement Tool to Assess Systematic Reviews; standardized effectiveness statements were generated. We found that RT was consistently a potent stimulus for increasing skeletal muscle mass (4/4 reviews provide some or sufficient evidence), strength (4/6 reviews provided some or sufficient evidence), and physical function (1/1 review provided some evidence). RT load (6/8 reviews provided some or sufficient evidence), weekly frequency (2/4 reviews provided some or sufficient evidence), volume (3/7 reviews provided some or sufficient evidence), and exercise order (1/1 review provided some evidence) impacted RT-induced increases in muscular strength. We discovered that 2/3 reviews provided some or sufficient evidence that RT volume and contraction velocity influenced skeletal muscle mass, while 4/7 reviews provided insufficient evidence in favor of RT load impacting skeletal muscle mass. There was insufficient evidence to conclude that time of day, periodization, inter-set rest, set configuration, set end point, contraction velocity/time under tension, or exercise order (only pertaining to hypertrophy) influenced skeletal muscle adaptations. A paucity of data limited insights into the impact of RT prescription variables on physical function.
CONCLUSION
Overall, RT increased muscle mass, strength, and physical function compared to no exercise. RT intensity (load) and weekly frequency impacted RT-induced increases in muscular strength but not muscle hypertrophy. RT volume (number of sets) influenced muscular strength and hypertrophy.
Topics: Adult; Humans; Resistance Training; Exercise Therapy; Exercise; Hypertrophy; Muscle, Skeletal
PubMed: 37385345
DOI: 10.1016/j.jshs.2023.06.005 -
Cell Metabolism Feb 2024The risk associated with multiple cancers, cardiovascular disease, diabetes, and all-cause mortality is decreased in individuals who meet the current recommendations for... (Review)
Review
The risk associated with multiple cancers, cardiovascular disease, diabetes, and all-cause mortality is decreased in individuals who meet the current recommendations for physical activity. Therefore, regular exercise remains a cornerstone in the prevention and treatment of non-communicable diseases. An acute bout of exercise results in the coordinated interaction between multiple tissues to meet the increased energy demand of exercise. Over time, the associated metabolic stress of each individual exercise bout provides the basis for long-term adaptations across tissues, including the cardiovascular system, skeletal muscle, adipose tissue, liver, pancreas, gut, and brain. Therefore, regular exercise is associated with a plethora of benefits throughout the whole body, including improved cardiorespiratory fitness, physical function, and glycemic control. Overall, we summarize the exercise-induced adaptations that occur within multiple tissues and how they converge to ultimately improve cardiometabolic health.
Topics: Humans; Exercise; Muscle, Skeletal; Cardiovascular System; Cardiovascular Diseases; Adipose Tissue
PubMed: 38183980
DOI: 10.1016/j.cmet.2023.12.008 -
Aging Cell Dec 2023The lifespan extension induced by 40% caloric restriction (CR) in rodents is accompanied by postponement of disease, preservation of function, and increased stress... (Randomized Controlled Trial)
Randomized Controlled Trial
The lifespan extension induced by 40% caloric restriction (CR) in rodents is accompanied by postponement of disease, preservation of function, and increased stress resistance. Whether CR elicits the same physiological and molecular responses in humans remains mostly unexplored. In the CALERIE study, 12% CR for 2 years in healthy humans induced minor losses of muscle mass (leg lean mass) without changes of muscle strength, but mechanisms for muscle quality preservation remained unclear. We performed high-depth RNA-Seq (387-618 million paired reads) on human vastus lateralis muscle biopsies collected from the CALERIE participants at baseline, 12- and 24-month follow-up from the 90 CALERIE participants randomized to CR and "ad libitum" control. Using linear mixed effect model, we identified protein-coding genes and splicing variants whose expression was significantly changed in the CR group compared to controls, including genes related to proteostasis, circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing/splicing, FOXO3 metabolism, apoptosis, and inflammation. Changes in some of these biological pathways mediated part of the positive effect of CR on muscle quality. Differentially expressed splicing variants were associated with change in pathways shown to be affected by CR in model organisms. Two years of sustained CR in humans positively affected skeletal muscle quality, and impacted gene expression and splicing profiles of biological pathways affected by CR in model organisms, suggesting that attainable levels of CR in a lifestyle intervention can benefit muscle health in humans.
Topics: Humans; Caloric Restriction; Longevity; Muscle, Skeletal; Muscle Strength
PubMed: 37823711
DOI: 10.1111/acel.13963 -
Nature Communications Jul 2023Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber...
Skeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive gene programs and how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq and ATAC-seq atlas of mouse skeletal muscle development at multiple stages of embryonic, fetal, and postnatal life. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca channels (Cav1.1), Maf expression and myofiber maturation are impaired. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction.
Topics: Mice; Animals; Muscle Fibers, Skeletal; Muscle, Skeletal; Gene Expression Regulation; Transcription Factors; Cell Differentiation
PubMed: 37468485
DOI: 10.1038/s41467-023-40073-8 -
Journal of Cachexia, Sarcopenia and... Oct 2023DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength....
BACKGROUND
DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored.
METHODS
Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects.
RESULTS
DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo.
CONCLUSIONS
Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.
Topics: Male; Humans; Animals; Female; Mice; Aged; Muscle, Skeletal; Muscular Atrophy; Muscle Fibers, Skeletal; Muscular Disorders, Atrophic; Mitochondria
PubMed: 37469245
DOI: 10.1002/jcsm.13290 -
International Journal of Molecular... Jun 2023Skeletal muscle is continuously exposed during its activities to mechanical/oxidative damage [...].
Skeletal muscle is continuously exposed during its activities to mechanical/oxidative damage [...].
Topics: Oxidative Stress; Muscle, Skeletal
PubMed: 37373372
DOI: 10.3390/ijms241210227