Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasi...Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasis and maintain physiological health during exercise stim-ulation.This article comprehensively examines the mechanisms and regulatory networks for governing ferroptosis and summarizes the impact of exercise and exerkines on ferroptosis under varying load intensities and disease contexts.Notably,despite its significant efficacy and minimal side effects, the therapeutic and prognostic potential of exercise in ferroptosis-related diseases remains largely unexplored.This article,by summarizing recent progresses in the regulation of exerkines-mediated ferroptosis,could further uncover the preventive or alleviative mecha-nisms of some diseases upon exercise interventions,which will be beneficial to design exercise interventional strategies for alleviating disease progression through the regulation of ferroptosis.展开更多
Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.T...Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.展开更多
Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secret...Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.展开更多
Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains...Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains unclear.Additionally,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase.We examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these associations.Methods:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included.IF1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year visit.Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations.Mediation analyses were conducted to examine whether apoA-I mediated these associations.Mixedeffect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA.Results:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly mediates this association.Additionally,this study finds that baseline concentrations of IF1 can predict future changes in PA.However,further research is needed to fully understand the mechanisms underlying these observations.展开更多
Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a ...Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.展开更多
Background:Angiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects.Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs(miRNAs)afte...Background:Angiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects.Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs(miRNAs)after exercise and found that some of them act as exerkines.However,whether these extracellular vesicle miRNAs mediate the exercise-induced angiogenesis remains unknown.Methods:A 9-day treadmill training was used as an exercise model in C57BL/6 mice.Liver-specific adeno-associated virus 8 was used to knock down microRNA-122-5p(miR-122-5p).Human umbilical vein endothelial cells were used in vitro.Results:Among these differentially expressed extracellular vesicle miRNAs,miR-122-5p was identified as a potent pro-angiogenic factor that activated vascular endothelial growth factor signaling and promoted angiogenesis both in vivo and in vitro.Exercise increased circulating levels of miR-122-5p,which was produced mainly by the liver and shuttled by extracellular vesicles in mice.Inhibition of circulating miR-122-5p or liver-specific knockdown of miR-122-5p significantly abolished the exercise-induced pro-angiogenic effect in skeletal muscles,and exerciseimproved muscle performance in mice.Mechanistically,miR-122-5p promoted angiogenesis through shifting substrate preference to fatty acids in endothelial cells,and miR-122-5p upregulated endothelial cell fatty-acid utilization by targeting 1-acyl-sn-glycerol-3-phosphate acyltransferase(AGPAT1).In addition,miR-122-5p increased capillary density in perilesional skin tissues and accelerated wound healing in mice.Conclusion:These findings demonstrated that exercise promotes angiogenesis through upregulation of liver-derived extracellular vesicle miR-122-5p,which enhances fatty acid utilization by targeting AGPAT1 in endothelial cells,highlighting the therapeutic potential of miR-122-5p in tissue repair.展开更多
Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors,including aging,malnutrition,denervation,and cardiovascular diseases,manifesting as the decline of...Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors,including aging,malnutrition,denervation,and cardiovascular diseases,manifesting as the decline of skeletal muscle mass and function.Both exercise and nutrition produce beneficial effects on skeletal muscle growth and are viewed as feasible strategies to prevent sarcopenia.Mechanisms involve regulating blood flow,oxidative stress,inflammation,apoptosis,protein synthesis and degradation,and satellite cell activation through exerkines and gut microbiomes.In this review,we summarized and discussed the latest progress and future development of the above mechanisms for providing a theoretical basis and ideas for the prevention and treatment of sarcopenia.展开更多
基金supported by the National Natural Science Foundation of China(No.32471186,No.32071176)the 14th Five-Year-Plan Advantageous and Characteristic Disci-plines(Groups)of Colleges and Universities in Hubei Prov-ince for Exercise and Brain Science from Hubei Provincial Department of Educationthe Leading Talent Program and Innovative Start-Up Foundation from Wuhan Sports University to NC.All figures were created by Figdraw(www.figdraw.com).
文摘Ferroptosis is a programmed cell death,and its mechanism involves multiple metabolic pathways,such as iron and lipid metabolism,and redox homeostasis.Exerkines are important mediators that optimize cellular homeostasis and maintain physiological health during exercise stim-ulation.This article comprehensively examines the mechanisms and regulatory networks for governing ferroptosis and summarizes the impact of exercise and exerkines on ferroptosis under varying load intensities and disease contexts.Notably,despite its significant efficacy and minimal side effects, the therapeutic and prognostic potential of exercise in ferroptosis-related diseases remains largely unexplored.This article,by summarizing recent progresses in the regulation of exerkines-mediated ferroptosis,could further uncover the preventive or alleviative mecha-nisms of some diseases upon exercise interventions,which will be beneficial to design exercise interventional strategies for alleviating disease progression through the regulation of ferroptosis.
基金the National Natural Science Foundation of China,No.82071372(to AL)the Natural Science Foundation of Guangdong Province of China,No.2021A1515011231(to AL)+1 种基金Outstanding Scholar Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory)of China,No.2018GZR110102002(to KFS and AL)Science and Technology Program of Guangzhou of China,No.202007030012(to KFS and AL).
文摘Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.
基金the Biochemical Imaging Center at UmeåUniversity and the National Microscopy Infrastructure(VR-RFI 2019-00217),for providing assistance in microscopy.
文摘Background Regular exercise training provides significant health benefits among cancer survivors and is associated with lower breast cancer mortality and reduced risk of recurrence.Both exercise-induced factors secreted into circulation(exerkines)and bioactive molecules contained in skeletal muscle secretome have been proposed to affect the tumor microenvironment and mediate some of the anti-carcinogenic effects of exercise.This study utilized exercise-conditioned human serum obtained from breast cancer patients during chemotherapy and skeletal myotubes’secretome after mechanical loading to investigate their effects on breast cancer cells in vitro.Methods Breast cancer patients participated in a 12-week exercise training program during their chemotherapy,and blood serum was collected immediately before and after an exercise session in the 2nd and 12th weeks of training.Skeletal myoblasts were differentiated into myotubes and subjected to mechanical stretching to collect their secretome(stretch medium(SM)).Hormone-sensitive Michigan Cancer Foundation-7(MCF-7)and triple-negative M.D.Anderson-Metastatic Breast-231(MDA-MB-231)breast cancer cells were treated with either human serum or with the skeletal myotubes’secretome to examine their metabolic activity,migration,cytotoxicity levels and apoptosis regulation.Results The exercise-conditioned serum obtained from breast cancer patients who were subjected to the 12-week training during chemotherapy resulted in reduced metabolic activity(p<0.001)and increased lactate dehydrogenase activity(cytotoxicity)(p<0.001)in both MCF-7 and MDA-MB-231 breast cancer cells when compared with the control condition.Moreover,incubation of breast cancer cells with the post-exercise serum induced apoptosis in MCF-7 and MDA-MB-231 cells,as indicated by increase in DNA damage and the percentage of necrotic cells(p<0.05)when compared to pre-exercise condition.Similarly,a significant decrease(p<0.001)was observed in the metabolic activity of MCF-7 cells treated with the SM,along with increased cytotoxicity(p<0.05),compared to the cells cultured with the regular growth media.Comparable though not as profound effects were observed in MDA-MB-231 cells when treated with the SM secretome.Furthermore,the expression of apoptosis-inducing Caspase-7(p<0.001)and Caspase-8(p<0.01)proteins was increased,whereas cell survival-regulating factors interleukin-8(IL-8)(p<0.001),superoxide dismutase-2(p<0.05),Fas cell surface death receptor(p<0.05),and vascular endothelial growth factor(p<0.01)were downregulated in the SM-treated MCF-7 cells.In addition,the migrating behavior of MCF-7 cells was diminished,and higher levels of DNA damage were observed in cells treated with either SM or non-stretch media.Conclusion Both exercise-conditioned serum of breast cancer patients and skeletal myotubes secretome after mechanical loading can reduce the metabolic activity,promote cell toxicity and DNA damage,modulate the protein expression of crucial cell survival-regulating factors,and lead to apoptosis in breast cancer cells.These findings suggest that even after cancer diagnosis,exercise may exert beneficial effects additive to chemotherapy against breast cancer prognosis.
基金supported by grants from the Region Occitanie/Pyrénées-Méditerranée(Grant No.1901175)the European Regional Development Fund(ERDF)(Grant No.MP0022856)+4 种基金This study received funding from la Fédération Française de Cardiologie”(FFC,Dotation Recherche),Alzheimer Prevention in Occitania and Catalonia(APOC Chair of Excellence-Inspire Program)Saint Louis University.The MAPT study was supported by grants from the Gérontopôle of Toulouse,the French Ministry of Health(PHRC 2008,2009)Pierre Fabre Research Institute(manufacturer of the omega-3 supplement)ExonHit Therapeutics SA,and Avid Radiopharmaceuticals,Inc.The promotion of this study was supported by the University Hospital Center of ToulouseThe data-sharing activity was supported by the Association Monegasque pour la Recherche sur la Maladie d'Alzheimer(AMPA)and the INSERM-University of Toulouse III UMR 1295(CERPOP)Research Unit.
文摘Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy metabolism.IF1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains unclear.Additionally,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP synthase.We examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these associations.Methods:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were included.IF1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year visit.Multiple linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 concentrations.Mediation analyses were conducted to examine whether apoA-I mediated these associations.Mixedeffect linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in PA.Results:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly mediates this association.Additionally,this study finds that baseline concentrations of IF1 can predict future changes in PA.However,further research is needed to fully understand the mechanisms underlying these observations.
基金supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (No. RGPIN 435807-13) to JPLthe ANZ-MASON foundation (to DB)supported by a Canadian Institutes of Health Research (CIHR) New Investigator Award (No. MSH-141980)
文摘Background: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training(HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6(IL-6), and recently identified myokines fibronectin type III domain-containing protein 5(FNDC5)(irisin) and meteorin-like protein(METRNL).Methods: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males(20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise(HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples(vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.Results: Before training, a single bout of HIIE increased IL-6(p < 0.05) and METRNL(p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest(both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training(p < 0.05), and there was an overall increase in FNDC5 mRNA post-training(main effect of training, p < 0.05).Conclusion: In human skeletal muscle(1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT;(2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and(3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.
基金supported by the National Key Basic Research Program of China(2019YFF0301600 and 2020YFC2002900)National Natural Science Foundation of China(31930055,31871146,32071169,81870273,and 32071108)Major Basic Science Program of Shaanxi Provincial Natural Science Foundation of China(2016ZDJC-17).
文摘Background:Angiogenesis constitutes a major mechanism responsible for exercise-induced beneficial effects.Our previous study identified a cluster of differentially expressed extracellular vesicle microRNAs(miRNAs)after exercise and found that some of them act as exerkines.However,whether these extracellular vesicle miRNAs mediate the exercise-induced angiogenesis remains unknown.Methods:A 9-day treadmill training was used as an exercise model in C57BL/6 mice.Liver-specific adeno-associated virus 8 was used to knock down microRNA-122-5p(miR-122-5p).Human umbilical vein endothelial cells were used in vitro.Results:Among these differentially expressed extracellular vesicle miRNAs,miR-122-5p was identified as a potent pro-angiogenic factor that activated vascular endothelial growth factor signaling and promoted angiogenesis both in vivo and in vitro.Exercise increased circulating levels of miR-122-5p,which was produced mainly by the liver and shuttled by extracellular vesicles in mice.Inhibition of circulating miR-122-5p or liver-specific knockdown of miR-122-5p significantly abolished the exercise-induced pro-angiogenic effect in skeletal muscles,and exerciseimproved muscle performance in mice.Mechanistically,miR-122-5p promoted angiogenesis through shifting substrate preference to fatty acids in endothelial cells,and miR-122-5p upregulated endothelial cell fatty-acid utilization by targeting 1-acyl-sn-glycerol-3-phosphate acyltransferase(AGPAT1).In addition,miR-122-5p increased capillary density in perilesional skin tissues and accelerated wound healing in mice.Conclusion:These findings demonstrated that exercise promotes angiogenesis through upregulation of liver-derived extracellular vesicle miR-122-5p,which enhances fatty acid utilization by targeting AGPAT1 in endothelial cells,highlighting the therapeutic potential of miR-122-5p in tissue repair.
基金funded by National Natural Science Foundation of China,grant number“32171128”.
文摘Sarcopenia is a progressive systemic skeletal muscle disease induced by various physiological and pathological factors,including aging,malnutrition,denervation,and cardiovascular diseases,manifesting as the decline of skeletal muscle mass and function.Both exercise and nutrition produce beneficial effects on skeletal muscle growth and are viewed as feasible strategies to prevent sarcopenia.Mechanisms involve regulating blood flow,oxidative stress,inflammation,apoptosis,protein synthesis and degradation,and satellite cell activation through exerkines and gut microbiomes.In this review,we summarized and discussed the latest progress and future development of the above mechanisms for providing a theoretical basis and ideas for the prevention and treatment of sarcopenia.
