Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia?

Sarcopenia is characterized by the progressive loss of skeletal muscle mass and strength. In older people, malnutrition and physical inactivity are often associated with sarcopenia, and, therefore, dietary interventions and exercise must be considered to prevent, delay, or treat it. Among the pathophysiological mechanisms leading to sarcopenia, a key role is played by an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and a decrease in enzymatic antioxidant protection leading to oxidative stress. Many studies have evaluated, in addition to the effects of exercise, the effects of antioxidant dietary supplements in limiting age-related muscle mass and performance, but the data which have been reported are conflicting. In skeletal muscle, ROS/RNS have a dual function: at low levels they increase muscle force and adaptation to exercise, while at high levels they lead to a decline of muscle performance. Controversial results obtained with antioxidant supplementation in older persons could in part reflect the lack of univocal effects of ROS on muscle mass and function. The purpose of this review is to examine the molecular mechanisms underlying the dual effects of ROS in skeletal muscle function and the analysis of literature data on dietary antioxidant supplementation associated with exercise in normal and sarcopenic subjects.

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The Effects of Aging and Training on Skeletal Muscle

The American Journal of Sports Medicine ◽

10.1177/03635465980260042401 ◽

1998 ◽

Vol 26 (4) ◽

pp. 598-602 ◽

Cited By ~ 130

Author(s):

Donald T. Kirkendall ◽

William E. Garrett

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Cellular Level ◽

Type I ◽

Loss Of Function ◽

Skeletal Muscle Function ◽

Cross Sectional ◽

Age Related ◽

General Slowing

Aging results in a gradual loss of muscle function, and there are predictable age-related alterations in skeletal muscle function. The typical adult will lose muscle mass with age; the loss varies according to sex and the level of muscle activity. At the cellular level, muscles loose both cross-sectional area and fiber numbers, with type II muscle fibers being the most affected by aging. Some denervation of fibers may occur. The combination of these factors leads to an increased percentage of type I fibers in older adults. Metabolically, the glycolytic enzymes seem to be little affected by aging, but the aerobic enzymes appear to decline with age. Aged skeletal muscle produces less force and there is a general “slowing” of the mechanical characteristics of muscle. However, neither reduced muscle demand nor the subsequent loss of function is inevitable with aging. These losses can be minimized or even reversed with training. Endurance training can improve the aerobic capacity of muscle, and resistance training can improve central nervous system recruitment of muscle and increase muscle mass. Therefore, physical activity throughout life is encouraged to prevent much of the age-related impact on skeletal muscle.

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NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

Journal of Frailty & Aging ◽

10.14283/jfa.2018.35 ◽

2018 ◽

pp. 1-3

Author(s):

B.C. Clark

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

The Past ◽

Conceptual Definition ◽

Age Related ◽

Per Se ◽

Definition Of ◽

And Function

Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.

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Age-Related Changes in Bone Mineral Density, Skeletal Muscle Mass, and Muscle Function in Postmenopausal Japanese Women

Journal of Clinical Densitometry ◽

10.1016/j.jocd.2014.04.061 ◽

2014 ◽

Vol 17 (3) ◽

pp. 415

Author(s):

T. Tachiki ◽

J. Kitagawa ◽

N. Takahira ◽

M. Iki ◽

J. Tamaki ◽

...

Keyword(s):

Bone Mineral Density ◽

Skeletal Muscle ◽

Muscle Mass ◽

Bone Mineral ◽

Muscle Function ◽

Skeletal Muscle Mass ◽

Japanese Women ◽

Mineral Density ◽

Age Related ◽

Age Related Changes

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Rationale for Antioxidant Supplementation in Sarcopenia

Journal of Aging Research ◽

10.1155/2012/316943 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 25

Author(s):

Francesco Cerullo ◽

Giovanni Gambassi ◽

Matteo Cesari

Keyword(s):

Oxidative Stress ◽

Muscle Function ◽

Molecular Mechanisms ◽

Motor Units ◽

Oxygen Species ◽

Antioxidant Supplementation ◽

Present Evidence ◽

Progressive Loss ◽

Age Related ◽

Prevention And Treatment

Sarcopenia is an age-related clinical condition characterized by the progressive loss of motor units and wasting of muscle fibers resulting in decreased muscle function. The molecular mechanisms leading to sarcopenia are not completely identified, but the increased oxidative damage occurring in muscle cells during the course of aging represents one of the most accepted underlying pathways. In fact, skeletal muscle is a highly oxygenated tissue and the generation of reactive oxygen species is particularly enhanced in both contracting and at rest conditions. It has been suggested that oral antioxidant supplementation may contribute at reducing indices of oxidative stress both in animal and human models by reinforcing the natural endogenous defenses. Aim of the present paper is to discuss present evidence related to possible benefits of oral antioxidants in the prevention and treatment of sarcopenia.

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Nutrition and microRNAs: Novel Insights to Fight Sarcopenia

Antioxidants ◽

10.3390/antiox9100951 ◽

2020 ◽

Vol 9 (10) ◽

pp. 951

Author(s):

Alessandra Barbiera ◽

Laura Pelosi ◽

Gigliola Sica ◽

Bianca Maria Scicchitano

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Molecular Mechanisms ◽

Muscle Protein ◽

Low Grade ◽

Protein Homeostasis ◽

Dietary Interventions ◽

Physiological Processes ◽

Age Related ◽

And Function

Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength, which may result in increased physical frailty and a higher risk of adverse events. Low-grade systemic inflammation, loss of muscle protein homeostasis, mitochondrial dysfunction, and reduced number and function of satellite cells seem to be the key points for the induction of muscle wasting, contributing to the pathophysiological mechanisms of sarcopenia. While a range of genetic, hormonal, and environmental factors has been reported to contribute to the onset of sarcopenia, dietary interventions targeting protein or antioxidant intake may have a positive effect in increasing muscle mass and strength, regulating protein homeostasis, oxidative reaction, and cell autophagy, thus providing a cellular lifespan extension. MicroRNAs (miRNAs) are endogenous small non-coding RNAs, which control gene expression in different tissues. In skeletal muscle, a range of miRNAs, named myomiRNAs, are involved in many physiological processes, such as growth, development, and maintenance of muscle mass and function. This review aims to present and to discuss some of the most relevant molecular mechanisms related to the pathophysiological effect of sarcopenia. Besides, we explored the role of nutrition as a possible way to counteract the loss of muscle mass and function associated with ageing, with special attention paid to nutrient-dependent miRNAs regulation. This review will provide important information to better understand sarcopenia and, thus, to facilitate research and therapeutic strategies to counteract the pathophysiological effect of ageing.

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Age-related changes in isolated mouse skeletal muscle function are dependent on sex, muscle, and contractility mode

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00073.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. R296-R314

Author(s):

Cameron Hill ◽

Rob S. James ◽

Val. M. Cox ◽

Frank Seebacher ◽

Jason Tallis

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Fatigue Resistance ◽

Muscle Function ◽

Isometric Force ◽

Muscle Quality ◽

Skeletal Muscle Function ◽

Cross Sectional ◽

Mouse Skeletal Muscle ◽

Age Related

The present study aimed to simultaneously examine the age-related, muscle-specific, sex-specific, and contractile mode-specific changes in isolated mouse skeletal muscle function and morphology across multiple ages. Measurements of mammalian muscle morphology, isometric force and stress (force/cross-sectional area), absolute and normalized (power/muscle mass) work-loop power across a range of contractile velocities, fatigue resistance, and myosin heavy chain (MHC) isoform concentration were measured in 232 isolated mouse (CD-1) soleus, extensor digitorum longus (EDL), and diaphragm from male and female animals aged 3, 10, 30, 52, and 78 wk. Aging resulted in increased body mass and increased soleus and EDL muscle mass, with atrophy only present for female EDL by 78 wk despite no change in MHC isoform concentration. Absolute force and power output increased up to 52 wk and to a higher level for males. A 23–36% loss of isometric stress exceeded the 14–27% loss of power normalized to muscle mass between 10 wk and 52 wk, although the loss of normalized power between 52 and 78 wk continued without further changes in stress ( P > 0.23). Males had lower power normalized to muscle mass than females by 78 wk, with the greatest decline observed for male soleus. Aging did not cause a shift toward slower contractile characteristics, with reduced fatigue resistance observed in male EDL and female diaphragm. Our findings show that the loss of muscle quality precedes the loss of absolute performance as CD-1 mice age, with the greatest effect seen in male soleus, and in most instances without muscle atrophy or an alteration in MHC isoforms.

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Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance

AJP Cell Physiology ◽

10.1152/ajpcell.00209.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1061-C1078 ◽

Cited By ~ 9

Author(s):

Nathan Hodson ◽

Daniel W. D. West ◽

Andrew Philp ◽

Nicholas A. Burd ◽

Daniel R. Moore

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Mass ◽

Human Skeletal Muscle ◽

Molecular Mechanisms ◽

Negative Impact ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Anabolic Resistance ◽

Age Related

Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status; therefore, much research has focused on understanding the molecular mechanisms that underpin this cellular process. Furthermore, older individuals display an attenuated MPS response to anabolic stimuli, termed anabolic resistance, which has a negative impact on muscle mass and function, as well as quality of life. Therefore, an understanding of which, if any, molecular mechanisms contribute to anabolic resistance of MPS is of vital importance in formulation of therapeutic interventions for such populations. This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. This review also summarizes evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance and provides recommendations for future avenues of research that can expand our knowledge of this area.

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Ang-(1–7) protects skeletal muscle function in aged mice

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04693-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ying Li ◽

Jiao Song ◽

Yangyang Jiang ◽

Xue Yang ◽

Li Cao ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Expression ◽

Muscle Function ◽

Molecular Mechanisms ◽

C2c12 Cells ◽

Skeletal Muscle Function ◽

Protective Function ◽

Aged Mice ◽

Age Related ◽

The Impact

Abstract Background The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang-(1–7)) axis has been shown to protect against the age-associated decline in skeletal muscle function. Here, we investigated the protective effects of ACE2 in mitigating the age-associated decline of skeletal muscle function and to identify the potential underlying molecular mechanisms. Methods We measured the expression levels of Ang-(1–7) in C57BL/6J mice of different ages and correlated these levels with measures of skeletal muscle function. We also investigated the expression of myocyte enhancer factor 2 A (MEF2A) in ACE2 knockout (ACE2KO) mice and its relationship with muscle function. We then treated aged ACE2KO mice for four weeks with Ang-(1–7) and characterized the levels of MEF2A and skeletal muscle function before and after treatment. We assessed the impact of Ang-(1–7) on the growth and differentiation of C2C12 cells in vitro and assessed changes in expression of the glucose transporter type 4 (Glut4). Results Aged mice showed reduced skeletal muscle function and levels of Ang-(1–7) expression in comparison to young and middle-aged mice. In ACE2KO mice, skeletal muscle function and MEF2A protein expression were significantly lower than in age-matched wild-type (WT) mice. After one month of Ang-(1–7) treatment, skeletal muscle function in the aged ACE2KO mice improved, while MEF2A protein expression was similar to that in the untreated group. In C2C12 cells, Ang-(1–7) was shown to promote along with the upregulated expression of Glut4. Conclusions The ACE2/ Ang-(1–7) axis has a protective function in skeletal muscle and administration of exogenous Ang-(1–7) can delay the age-related decline in the function of skeletal muscle.

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High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway

10.1101/347120 ◽

2018 ◽

Author(s):

Renato Ferretti ◽

Eliezer Guimarães Moura ◽

Veridiana Carvalho dos Santos ◽

Eduardo José Caldeira ◽

Marcelo Conte ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Training ◽

Muscle Mass ◽

High Fat Diet ◽

Muscle Function ◽

Mtor Pathway ◽

Muscle Performance ◽

High Fat ◽

Negative Effects ◽

Obesity And Diabetes

AbstractHigh-fat (HF) diets in combination with sedentary lifestyle represent one of the major public health concerns predisposing to obesity and diabetes leading to skeletal muscle atrophy, decreased fiber diameter and muscle mass with accumulation of fat tissue resulting in loss of muscle strength. One strategy to overcome the maleficent effects of HF diet is resistance training, a strategy used to improve muscle mass, reverting the negative effects on obesity-related changes in skeletal muscle. Together with resistance training, supplementation with creatine monohydrate (CrM) in the diet has been used to improve muscle mass and strength. Creatine is a non-essential amino acid that is directly involved in the cross-bridge cycle providing a phosphate group to ADP during the initiation of muscle contraction. Besides its antioxidant and anti-inflammatory effects CrM also upregulates IGF-1 resulting in hyperthophy with an increase in muscle function. However, it is unknown whether CrM supplementation during resistance training would revert the negative effects of high-fat diet on the muscle performance. During 8 weeks we measured muscle performance to climb a 1.1m and 80° ladder with increasing load on trained rats that had received standard diet or high-fat diet, supplemented or not with CrM. We observed that the CrM supplementation up-regulated IGF-1 and phospho-AKT protein levels, suggesting an activation of the IGF1-PI3K-Akt/PKB-mTOR pathway. Moreover, despite the CrM supplementation, HF diet down-regulated several proteins of the IGF1-PI3K-Akt/PKB-mTOR pathway, suggesting that diet lipid content is crucial to maintain or improve muscle function during resistance training.

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