scholarly journals Mitochondrial Impairment in Sarcopenia

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
Francesco Bellanti ◽  
Aurelio Lo Buglio ◽  
Gianluigi Vendemiale
Keyword(s):  
Skeletal Muscle ◽  
Muscle Quality ◽  
Protein Homeostasis ◽  
Related Condition ◽  
Selective Autophagy ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Alterations ◽  
Mitochondrial Impairment ◽  
Age Related ◽  
And Function

Sarcopenia is defined by the age-related loss of skeletal muscle quality, which relies on mitochondrial homeostasis. During aging, several mitochondrial features such as bioenergetics, dynamics, biogenesis, and selective autophagy (mitophagy) are altered and impinge on protein homeostasis, resulting in loss of muscle mass and function. Thus, mitochondrial dysfunction contributes significantly to the complex pathogenesis of sarcopenia, and mitochondria are indicated as potential targets to prevent and treat this age-related condition. After a concise presentation of the age-related modifications in skeletal muscle quality and mitochondrial homeostasis, the present review summarizes the most relevant findings related to mitochondrial alterations in sarcopenia.

scholarly journals Nutrition and microRNAs: Novel Insights to Fight Sarcopenia

Antioxidants ◽  
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.

scholarly journals Superoxide Anion Production and Bioenergetic Profile in Young and Elderly Human Primary Myoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Mariangela Marrone ◽  
Rita Maria Laura La Rovere ◽  
Simone Guarnieri ◽  
Ester Sara Di Filippo ◽  
Giovanni Monaco ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Energy Demand ◽  
The Elderly ◽  
Compensatory Mechanisms ◽  
Superoxide Anion Production ◽  
Age Related ◽  
Primary Myoblasts ◽  
Production Variability ◽  
And Function

Sarcopenia is the age-related loss of skeletal muscle mass, strength, and function. It is associated with regenerative difficulties by satellite cells, adult muscle stem cells, and alteration of oxidative management, mainly the increase in superoxide anions (O2•−). We aimed to investigate the relation between regenerative deficit in elderly and increase in O2•− production along with mitochondrial alterations. Myoblasts and myotubes from skeletal muscle of young and elderly healthy subjects (27.8 ± 6 and 72.4 ± 6.5 years old) were measured: (1) superoxide dismutase activity and protein content, (2) mitochondrial O2•− production levels, (3) O2•− production variability, and (4) mitochondrial bioenergetic profile. Compared to young myoblasts, elderly myoblasts displayed decreased SOD2 protein expression, elevated mitochondrial O2•− baseline levels, and decreased oxidative phosphorylation and glycolysis. Additionally, elderly versus young myotubes showed elevated mitochondrial O2•− levels when stressed with N-acetyl cysteine or high glucose and higher glycolysis despite showing comparable oxidative phosphorylation levels. Altogether, the elderly may have less metabolic plasticity due to the impaired mitochondrial function caused by O2•−. However, the increased energy demand related to the differentiation process appears to activate compensatory mechanisms for the partial mitochondrial dysfunction.

scholarly journals NEUROMUSCULAR CHANGES WITH AGING AND SARCOPENIA

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.

scholarly journals Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

2020 ◽  
Vol 21 (15) ◽  
pp. 5236 ◽  
Author(s):  
Evelyn Ferri ◽  
Emanuele Marzetti ◽  
Riccardo Calvani ◽  
Anna Picca ◽  
Matteo Cesari ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cellular Senescence ◽  
Significant Loss ◽  
Muscle Aging ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Health Quality ◽  
Skeletal Muscle Aging ◽  
And Function

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

Skeletal Muscle Mass Regulation in Critical Illness

2014 ◽  
Author(s):  
Zudin Puthucheary ◽  
Hugh Montgomery ◽  
Nicholas Hart ◽  
Stephen Harridge
Keyword(s):  
Skeletal Muscle ◽  
Critical Illness ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Bed Rest ◽  
Protein Homeostasis ◽  
Highly Sensitive ◽  
And Function ◽  
Inadequate Nutrition

Muscle is a dynamic, plastic, and malleable tissue that is highly sensitive to mechanical and metabolic signals. Muscle mass is regulated by protein homeostasis, with protein being continually turned over, reflecting a balance between synthesis and breakdown. This chapter discusses the effect of critical illness on skeletal muscle mass, protein homeostasis, and the intracellular signalling driving anabolism and catabolism. The focus will be on the unique challenges to which the skeletal muscle are exposed, such as inflammation, sepsis, sedation, and inadequate nutrition, which, in combination with the disuse signals of immobilization and bed rest, engender dramatic changes in muscle structure and function. The mechanisms regulating muscle loss during critical illness are being unravelled, but many questions remain unanswered. Detailed understanding of these mechanisms will help drive strategies to minimize or prevent intensive care-acquired muscle weakness and the long-term consequences experienced by ICU survivors.

Effects of Ageing on the Motor Unit: A Brief Review

1993 ◽  
Vol 18 (4) ◽  
pp. 331-358 ◽  
Author(s):  
Timothy J. Doherty ◽  
Anthony A. Vandervoort ◽  
William F. Brown
Keyword(s):  
Skeletal Muscle ◽  
Relaxation Times ◽  
Motor Units ◽  
The Elderly ◽  
Key Words Skeletal Muscle ◽  
Current State ◽  
Age Related ◽  
Human Motor ◽  
Muscle Groups ◽  
And Function

This review briefly summarizes the current state of knowledge regarding age related changes in skeletal muscle, followed by a more in-depth review of ageing effects on animal and human motor units (MUs). Ageing in humans is generally associated with reductions in muscle mass (atrophy), leading to reduced voluntary and electrically evoked contractile strength by the 7th decade for most muscle groups studied. As well, contraction and one-half relaxation times are typically prolonged in muscles of the elderly. Evidence from animal and human studies points toward age associated MU loss as the primary mechanism for muscle atrophy, and such losses may be greatest among the largest and fastest MUs. However, based on studies in animals and humans, it appears that at least some of the surviving MUs are able to partially compensate for MU losses, as indicated by an increase in the average MU size with age. The fact that muscles in the elderly have fewer, but on average larger and slower, MUs has important implications for motor control and function in this population. Key words: skeletal muscle, motor neuron, motor axon, contractile properties, adaptation

scholarly journals Troponin Variants as Markers of Skeletal Muscle Health and Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Monica Rasmussen ◽  
Jian-Ping Jin
Keyword(s):  
Skeletal Muscle ◽  
Troponin I ◽  
Striated Muscle ◽  
Troponin T ◽  
Muscle Quality ◽  
Striated Muscles ◽  
Thin Filaments ◽  
Age Related ◽  
Development And Aging ◽  
Regulation Of Muscle Contraction

Ca2+-regulated contractility is a key determinant of the quality of muscles. The sarcomeric myofilament proteins are essential players in the contraction of striated muscles. The troponin complex in the actin thin filaments plays a central role in the Ca2+-regulation of muscle contraction and relaxation. Among the three subunits of troponin, the Ca2+-binding subunit troponin C (TnC) is a member of the calmodulin super family whereas troponin I (TnI, the inhibitory subunit) and troponin T (TnT, the tropomyosin-binding and thin filament anchoring subunit) are striated muscle-specific regulatory proteins. Muscle type-specific isoforms of troponin subunits are expressed in fast and slow twitch fibers and are regulated during development and aging, and in adaptation to exercise or disuse. TnT also evolved with various alternative splice forms as an added capacity of muscle functional diversity. Mutations of troponin subunits cause myopathies. Owing to their physiological and pathological importance, troponin variants can be used as specific markers to define muscle quality. In this focused review, we will explore the use of troponin variants as markers for the fiber contents, developmental and differentiation states, contractile functions, and physiological or pathophysiological adaptations of skeletal muscle. As protein structure defines function, profile of troponin variants illustrates how changes at the myofilament level confer functional qualities at the fiber level. Moreover, understanding of the role of troponin modifications and mutants in determining muscle contractility in age-related decline of muscle function and in myopathies informs an approach to improve human health.

scholarly journals SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Ramu Manjula ◽  
Kumari Anuja ◽  
Francisco J. Alcain
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Histone Deacetylases ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Life Extension ◽  
Protein Homeostasis ◽  
Brain Functions ◽  
Age Related ◽  
And Function

Sirtuins are NAD+ dependent histone deacetylases (HDAC) that play a pivotal role in neuroprotection and cellular senescence. SIRT1-7 are different homologs from sirtuins. They play a prominent role in many aspects of physiology and regulate crucial proteins. Modulation of sirtuins can thus be utilized as a therapeutic target for metabolic disorders. Neurological diseases have distinct clinical manifestations but are mainly age-associated and due to loss of protein homeostasis. Sirtuins mediate several life extension pathways and brain functions that may allow therapeutic intervention for age-related diseases. There is compelling evidence to support the fact that SIRT1 and SIRT2 are shuttled between the nucleus and cytoplasm and perform context-dependent functions in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). In this review, we highlight the regulation of SIRT1 and SIRT2 in various neurological diseases. This study explores the various modulators that regulate the activity of SIRT1 and SIRT2, which may further assist in the treatment of neurodegenerative disease. Moreover, we analyze the structure and function of various small molecules that have potential significance in modulating sirtuins, as well as the technologies that advance the targeted therapy of neurodegenerative disease.

scholarly journals An investigation of p53 in skeletal muscle aging

2019 ◽  
Vol 127 (4) ◽  
pp. 1075-1084 ◽  
Author(s):  
Scott M. Ebert ◽  
Jason M. Dierdorff ◽  
David K. Meyerholz ◽  
Steven A. Bullard ◽  
Asma Al-Zougbi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Fibers ◽  
Skeletal Muscle Atrophy ◽  
P53 Expression ◽  
Skeletal Muscle Fibers ◽  
Age Related ◽  
Skeletal Muscle Aging ◽  
And Function

Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53 may play a central, causative role in skeletal muscle aging, whereas other, apparently contradictory lines of evidence have suggested that p53 may be critical for normal skeletal muscle function. To help address these issues, we performed an aging study in male muscle-specific p53-knockout mice (p53 mKO mice), which have a lifelong absence of p53 expression in skeletal muscle fibers. We found that the absence of p53 expression in skeletal muscle fibers had no apparent deleterious or beneficial effects on skeletal muscle mass or function under basal conditions up to 6 mo of age, when mice are fully grown and exhibit peak muscle mass and function. Furthermore, at 22 and 25 mo of age, when age-related muscle weakness and atrophy are clearly evident in mice, p53 mKO mice demonstrated no improvement or worsening of skeletal muscle mass or function relative to littermate control mice. At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice. In light of these results, we conclude that p53 expression in skeletal muscle fibers has minimal if any direct, cell autonomous effect on basal or age-related changes in skeletal muscle mass and function up to at least 22 mo of age. NEW & NOTEWORTHY Previous studies implicated the transcriptional regulator p53 as a potential mediator of age-related skeletal muscle weakness and atrophy. We tested this hypothesis by investigating the effect of aging in muscle-specific p53-knockout mice. Our results strongly suggest that p53 activity within skeletal muscle fibers is not required for age-related skeletal muscle atrophy or weakness.

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