Sarcopenia: Aging-Related Loss of Muscle Mass and Function

Larsson, Lars; Degens, Hans; Li, Meishan; Salviati, Leonardo; Lee, Youngil; Thompson, Wesley J.; Kirkland, James L.; Sandri, Marco

doi:10.1152/physrev.00061.2017

Cited by 959 publications

(873 citation statements)

References 961 publications

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“…Indeed, it is well documented that the deterioration of gait speed related to sarcopenia during aging is due to quantitative and qualitative changes in muscle structure and function. 1 We also found that the lower the gait speed, the greater dependency, which is in accord with the literature on this topic, 6,33 in which a lower gait speed is related to more problems in ADL. Accordingly, physical activity focused on counteracting the decline in gait speed could prevent functional dependency.…”

Section: Discussionsupporting

confidence: 90%

“…Sarcopenia is an age‐related loss of muscle mass and function in older adults and may favour the appearance of cardiovascular complications or neurodegenerative disorders. While its prevalence is variable depending on its localization and the method of evaluation, it is estimated that 29% of older persons in community‐dwelling populations and 14–33% in long‐term care populations are affected by sarcopenia .…”

Section: Introductionmentioning

confidence: 99%

“…As a locomotor capacity, gait speed is representative of neuromuscular quality (morphological and neuronal) and a critical determining factor for healthy aging. Indeed, the European Working Group on Sarcopenia in Older People has developed an algorithm including gait speed measurement as the easiest and most reliable way to determine sarcopenia in clinical practice, and also this has been used to diagnose functional disability and dependence in older adults .…”

Section: Introductionmentioning

confidence: 99%

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Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living

Pérez-Sousa

Venegas-Sanabria

Chavarro-Carvajal

et al. 2019

J cachexia sarcopenia muscle

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Background Sarcopenia in older adults is strongly associated with an increase in dependency in activities of daily living (ADL) and with a decline in gait speed. Interestingly, gait speed has been shown to independently predict mortality. In this context, our study aimed to explore the mediator role of gait speed on the relationship between sarcopenia and dependency in ADL. Methods A cross‐sectional study was conducted in Colombia, 19 705 older adults with a mean age of 70 years, 55.6% women, 16.1% with sarcopenia, and 14.7% mild, moderate, or severe dependency in ADL, according to ‘SABE Survey 2015’. Sarcopenia was assessed by calf circumference and ADL dependence through the Barthel Index. Gait speed was measured over a distance of 3 m. The association between sarcopenia condition and gait speed and dependency level was analysed by linear regression adjusted by covariates. To examine whether gait speed mediated the association between sarcopenia and dependence components of physical function, simple mediation models were generated using ordinary least squares with the macro PROCESS version 3.2, adjusted for age, sex, and body mass index (BMI). Results Significant differences (P < 0.05) were found in gait speed and dependency in ADL between the sarcopenia and non‐sarcopenia groups after adjusting for age, sex, and BMI. BMI was significantly higher in the non‐sarcopenia group whereas dependency was significantly higher in the sarcopenia group (19.6% vs. 13.8%). Results from mediation model regression analysis indicated a significant and direct detrimental effect of sarcopenia on dependency in ADL (β = −0.05; P < 0.001), and a significant indirect effect of gait speed on the direct effect (−0.009 to −0.004). Conclusions The negative effect of sarcopenia on functional dependence was mediated by the gait speed. Therefore, gait speed may positively influence the detrimental effect of sarcopenia for dependency, after adjusting for age, gender, and BMI. Consequently, physical exercise should be promoted and focused to circumvent the gait speed decline associated with age in older people with sarcopenia.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living

Pérez-Sousa

Venegas-Sanabria

Chavarro-Carvajal

et al. 2019

J cachexia sarcopenia muscle

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“…Skeletal muscle atrophy is a well-known consequence of the ageing process and is the result of both a reduction in muscle fibre number and selective atrophy of the remaining muscle fibres (Larsson et al 2019). It is often noted that different muscle fibre types are affected by the atrophy process to different degrees, with many studies concluding that type II fibres atrophy more than do type I fibres with ageing (Lexell et al 1988;Nilwik et al 2013;St-Jean-Pelletier et al 2017).…”

Section: Changes In Muscle Fibre Size and Proportion With Advanced Agementioning

confidence: 99%

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women

Sonjak

Jacob

Morais

et al. 2019

The Journal of Physiology

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Key points Susceptibility to age‐related muscle atrophy relates to the degree of muscle denervation and the capacity of successful reinnervation. However, the specific role of denervation as a determinant of the severity of muscle aging between populations with low versus high physical function has not been addressed. We show that prefrail/frail elderly women exhibited marked features of muscle denervation, whereas world class octogenarian female master athletes showed attenuated indices of denervation and greater reinnervation capacity. These findings suggest that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibers. Abstract Ageing muscle degeneration is a key contributor to physical frailty; however, the factors responsible for exacerbated vs. muted ageing muscle impact are largely unknown. Based upon evidence that susceptibility to neurogenic impact is an important determinant of the severity of ageing muscle degeneration, we aimed to determine the presence and extent of denervation in pre‐frail/frail elderly (FE, 77.9 ± 6.2 years) women compared to young physically inactive (YI, 24.0 ± 3.5 years) females, and contrast these findings to high‐functioning world class octogenarian female masters athletes (MA, 80.9 ± 6.6 years). Muscle biopsies from vastus lateralis muscle were obtained from all three groups to assess denervation‐related morphological and transcriptional markers. The FE group displayed marked grouping of slow fibres, accumulation of very small myofibres, a severe reduction in type IIa/I size ratio, highly variable inter‐subject accumulation of neural cell adhesion molecule (NCAM)‐positive myofibres, and an accumulation of pyknotic nuclei, indicative of recurring cycles of denervation/reinnervation and persistent denervation. The MA group exhibited a smaller decline in type IIa/I size ratio and fewer pyknotic nuclei, accompanied by a higher degree of type I fibre grouping and larger fibre group size, suggesting a greater reinnervation of denervated fibres. Consistent with this interpretation, MA had higher mRNA levels of the reinnervation‐promoting cytokine fibroblast growth factor binding protein 1 (FGFBP1) than FE. Our results indicate that the muscle of FE women has significant neurogenic atrophy, whereas MA muscle exhibit superior reinnervation capacity, suggesting that the difference in age‐related muscle impact between low‐ and high‐functioning elderly women is the robustness of the response to denervation of myofibres.

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confidence: 99%

Parkin the progression of sarcopenia

Henríquez‐Olguín

Knudsen

2019

The Journal of Physiology

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Skeletal muscle mass and function decline progressively during ageing. Since this is associated with susceptibility to chronic diseases, metabolic dysfunction, physical frailty and an overall reduction in quality of life, age-related loss of muscle function negatively affects the daily life of millions of people (Larsson et al. 2019). To battle age-related loss of muscle function, improving our understanding of the underlying cellular mechanisms is crucial.Altered mitochondrial protein homeostasis during ageing has been proposed to mediate the age-related loss of muscle function. Studies of skeletal muscle from aged rodents and humans demonstrated that these alterations were associated with the accumulation of damaged and/or dysfunctional mitochondria (Larsson et al. 2019).Old/damaged mitochondria are removed by a selective autophagy-process called mitophagy (Drake & Yan, 2017). Although no direct evidence has been published, impaired removal of damaged dysfunctional mitochondria through mitophagy has been suggested to contribute to ageing-associated pathologies in muscle. Thus, a mechanistic understanding of mitophagy might provide new drug targets to combat age-related decline in muscle function. A key initial step in mitophagy is the recognition of damaged mitochondria. In basal conditions, the mitochondrially targeted kinase PTEN-induced kinase 1 (PINK1) is degraded by mitochondrial proteases. PINK1 accumulates on the outer membrane of depolarized mitochondria. This results in recruitment and phosphorylation of the E3 ubiquitin ligase Parkin. Activated Parkin induces ubiquitination of mitochondrial outer membrane proteins. This triggers activation of the ubiquitin-proteasome system and recruitment of autophagy receptors. Subsequently, the damaged mitochondrial component(s) are engulfed by autophagosomes. A recent article in The Journal of Physiology by Leduc-Gaudet et al. (2019) evaluated the impact of Parkin overexpression on ageing-related loss of muscle mass and function. The authors hypothesized that an ageing-related impairment in mitophagy would lead to accumulation of dysfunctional mitochondria and cause sarcopenia. To test this, the authors injected adeno-associated virus (AAV) vectors encoding Parkin or green fluorescent protein (GFP; contralateral control) intramuscularly into legs of either young or old mice. Overall the authors demonstrated a number of important findings as discussed below. These warrant further research into the effect of Parkin on age-related loss of muscle function. Involvement of Parkin in age-related muscle dysfunctionFirst, the authors demonstrated that aged muscles displayed reduced Parkin expression compared to muscles from young mice (GFP-control legs). Furthermore, Parkin was markedly higher in tibialis anterior muscle from both young and old AAV-Parkin-injected legs. The changes in Parkin expression, both with ageing and with AAV-Parkin injection, were paralleled by changes in fibre size and muscle mass. Importantly, Parkin overexpression increased muscle function measu...

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Sarcopenia: Aging-Related Loss of Muscle Mass and Function

Cited by 959 publications

References 961 publications

Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living

Gait speed as a mediator of the effect of sarcopenia on dependency in activities of daily living

Fidelity of muscle fibre reinnervation modulates ageing muscle impact in elderly women

Parkin the progression of sarcopenia

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