scholarly journals MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Yun-Fei Yang ◽  
Wu Yang ◽  
Zhi-Yin Liao ◽  
Yong-Xin Wu ◽  
Zhen Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Calcium Uptake ◽  
Mitochondrial Calcium ◽  
Muscle Aging ◽  
Skeletal Muscle Aging ◽  
And Function ◽  
Mitochondrial Calcium Uptake

AbstractAge-related loss of skeletal muscle mass and function, termed sarcopenia, could impair the quality of life in the elderly. The mechanisms involved in skeletal muscle aging are intricate and largely unknown. However, more and more evidence demonstrated that mitochondrial dysfunction and apoptosis also play an important role in skeletal muscle aging. Recent studies have shown that mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium affects skeletal muscle mass and function by affecting mitochondrial function. During aging, we observed downregulated expression of mitochondrial calcium uptake family member3 (MICU3) in skeletal muscle, a regulator of MCU, which resulted in a significant reduction in mitochondrial calcium uptake. However, the role of MICU3 in skeletal muscle aging remains poorly understood. Therefore, we investigated the effect of MICU3 on the skeletal muscle of aged mice and senescent C2C12 cells induced by d-gal. Downregulation of MICU3 was associated with decreased myogenesis but increased oxidative stress and apoptosis. Reconstitution of MICU3 enhanced antioxidants, prevented the accumulation of mitochondrial ROS, decreased apoptosis, and increased myogenesis. These findings indicate that MICU3 might promote mitochondrial Ca2+ homeostasis and function, attenuate oxidative stress and apoptosis, and restore skeletal muscle mass and function. Therefore, MICU3 may be a potential therapeutic target in skeletal muscle aging.

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.

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.

scholarly journals Sarcopenia in women with hip fracture: A comparison of hormonal biomarkers and their relationship to skeletal muscle mass and function

2020 ◽  
Vol 6 (3) ◽  
pp. 139-145
Author(s):  
Ming Li Yee ◽  
Raphael Hau ◽  
Alison Taylor ◽  
Mark Guerra ◽  
Peter Guerra ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hip Fracture ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
And Function

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.

scholarly journals Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments

2020 ◽  
Vol 55 (10) ◽  
pp. 927-943 ◽  
Author(s):  
Giovanni Marasco ◽  
Matteo Serenari ◽  
Matteo Renzulli ◽  
Luigina Vanessa Alemanni ◽  
Benedetta Rossini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Appropriate Treatment ◽  
Risk Of Mortality ◽  
Short And Long Term ◽  
Poor Outcomes ◽  
And Function

Abstract Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

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