Mitochondria Initiate and Regulate Sarcopenia

Alway, Stephen E.; Mohamed, Junaith S.; Myers, Matthew J.

doi:10.1249/jes.0000000000000101

Cited by 97 publications

(77 citation statements)

References 151 publications

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“…There is likely a link between mitochondrial dysfunction and aging including sarcopenia . As SIRT1 is a known regulator of PGC1α which in turn regulates mitochondria biogenesis, we next decided to investigate the effects that SIRT1 expression levels had on mitochondrial activity in the skeletal muscle of older mice.…”

Section: Resultsmentioning

confidence: 99%

“…Sarcopenia is accompanied by an increased risk for physical disabilities, fall‐induced injuries, hospitalization/institutionalization, and mortality, and it is exacerbated by obesity and metabolic disorders . Mitochondria regulate muscle metabolism and mitochondrial dysfunction may play a role in sarcopenia . Indeed, altered size and granularity have been observed in aging mitochondria, as well as in the mitochondria of subjects diagnosed with type 2 diabetes mellitus .…”

Section: Introductionmentioning

confidence: 99%

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The role of SIRT1 in skeletal muscle function and repair of older mice

Myers

Shepherd

Durr

et al. 2019

J cachexia sarcopenia muscle

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Background Sirtuin 1 (SIRT1) is a NAD+ sensitive deacetylase that has been linked to longevity and has been suggested to confer beneficial effects that counter aging‐associated deterioration. Muscle repair is dependent upon satellite cell function, which is reported to be reduced with aging; however, it is not known if this is linked to an aging‐suppression of SIRT1. This study tested the hypothesis that Sirtuin 1 (SIRT1) overexpression would increase the extent of muscle repair and muscle function in older mice. Methods We examined satellite cell dependent repair in tibialis anterior, gastrocnemius, and soleus muscles of 13 young wild‐type mice (20–30 weeks) and 49 older (80+ weeks) mice that were controls ( n = 13), overexpressed SIRT1 in skeletal muscle ( n = 14), and had a skeletal muscle SIRT1 knockout ( n = 12) or a satellite cell SIRT1 knockout ( n = 10). Acute muscle injury was induced by injection of cardiotoxin (CTX), and phosphate‐buffered saline was used as a vector control. Plantarflexor muscle force and fatigue were evaluated before or 21 days after CTX injection. Satellite cell proliferation and mitochondrial function were also evaluated in undamaged muscles. Results Maximal muscle force was significantly lower in control muscles of older satellite cell knockout SIRT1 mice compared to young adult wild‐type (YWT) mice ( P < 0.001). Mean contraction force at 40 Hz stimulation was significantly greater after recovery from CTX injury in older mice that overexpressed muscle SIRT1 than age‐matched SIRT1 knockout mice ( P < 0.05). SIRT1 muscle knockout models (P < 0.05) had greater levels of p53 (P < 0.05 MKO, P < 0.001 OE) in CTX‐damaged tissues as compared to YWT CTX mice. SIRT1 overexpression with co‐expression of p53 was associated with increased fatigue resistance and increased force potentiation during repeated contractions as compared to wild‐type or SIRT1 knockout models ( P < 0.001). Muscle structure and mitochondrial function were not different between the groups, but proliferation of satellite cells was significantly greater in older mice with SIRT1 muscle knockout ( P < 0.05), but not older SIRT1 satellite cell knockout models, in vitro , although this effect was attenuated in vivo after 21 days of recovery. Conclusions The data suggest skeletal muscle structure, function, and recovery after CTX‐induced injury are not significantly influenced by gain or loss of SIRT1 abundance alone in skeletal muscle; however, muscle function is impaired by ablation of SIRT1 in satellite cells. SIRT1 appears to interact with p53 to improve muscle fatigue resistance after repair from muscle injur...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of SIRT1 in skeletal muscle function and repair of older mice

Myers

Shepherd

Durr

et al. 2019

J cachexia sarcopenia muscle

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“…Specifically, age‐related muscle loss has been linked to increased reactive oxygen species (ROS) production, increased mitochondrial apoptotic susceptibility, decline in mitochondrial respiratory chain function, reduced transcriptional drive for mitochondrial biogenesis, and morphological changes in mitochondria; and also, most, but not all, studies state that the capacity to mobilize and/or oxidize IMCL is substantially impaired in older individuals. In congruence with this, it has recently been suggested that accumulation of dysfunctional mitochondria initiate a signalling cascade leading to motor neuron and muscle fibre death and culminating in muscle loss (Figure ) . Not all studies point in the same direction though, and a number of articles raised doubts concerning mitochondrial dysfunction as a causal factor in the development of insulin resistance and muscle atrophy .…”

Section: Determinants Of Muscle Massmentioning

confidence: 98%

Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes

2019

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Summary Insulin resistance and muscle mass loss often coincide in individuals with type 2 diabetes. Most patients with type 2 diabetes are overweight, and it is well established that obesity and derangements in lipid metabolism play an important role in the development of insulin resistance in these individuals. Specifically, increased adipose tissue mass and dysfunctional adipose tissue lead to systemic lipid overflow and to low‐grade inflammation via altered secretion of adipokines and cytokines. Furthermore, an increased flux of fatty acids from the adipose tissue may contribute to increased fat storage in the liver and in skeletal muscle, resulting in an altered secretion of hepatokines, mitochondrial dysfunction, and impaired insulin signalling in skeletal muscle. Recent studies suggest that obesity and lipid derangements in adipose tissue can also lead to the development of muscle atrophy, which would make insulin resistance and muscle atrophy two sides of the same coin. Unfortunately, the exact relationship between lipid accumulation, type 2 diabetes, and muscle atrophy remains largely unexplored. The aim of this review is to discuss the relationship between type 2 diabetes and muscle loss and to discuss some of the joint pathways through which lipid accumulation in organs may affect peripheral insulin sensitivity and muscle mass.

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“…Mitochondria play a critical role in maintaining skeletal muscle mass . Aging is associated with an increase in reactive oxygen species and mitochondrial stress, which induces mitochondrial dysfunction . When mitochondrial content is released into the cell cytosol due to mitochondrial stress, nucleus damage occurs and eventually results in the death of the entire muscle cell .…”

Section: Introductionmentioning

confidence: 99%

“…Aging is associated with an increase in reactive oxygen species and mitochondrial stress, which induces mitochondrial dysfunction . When mitochondrial content is released into the cell cytosol due to mitochondrial stress, nucleus damage occurs and eventually results in the death of the entire muscle cell . Exercise enhances mitochondrial biogenesis and may protect against the age‐associated apoptosis of muscle cells and muscle wasting .…”

Section: Introductionmentioning

confidence: 99%

Hydrangea serrata Tea Enhances Running Endurance and Skeletal Muscle Mass

Jang

Ahn

Son

et al. 2019

Molecular Nutrition Food Res

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Scope Skeletal muscle mass and quality can be negatively affected by aging, inactivity, and disease, while a loss of muscle mass is associated with chronic disease status, falls, and mortality. We investigate the effects of Hydrangea serrata on skeletal muscle mass and function, along with the underlying mechanisms. Methods and results H. serrata, identified through MyoD transcription activity screening, increases myogenic differentiation via Akt and p38. C57BL/6 mice are fed a 0.25% or 0.5% H. serrata diet for 8 weeks. H. serrata increased treadmill running distance and maximum speed, as well as skeletal muscle mass. H. serrata promotes the expression of myosin heavy chain 1 (MHC1) and MHC2A but not MHC2B. H. serrata also upregulates the protein expression of peroxisome proliferator‐activated receptor δ (PPARδ) and mitochondrial complexes, and enhances citrate synthase and mitochondrial complex І activity. Transforming growth factor‐β (TGF‐β), myostatin, and growth differentiation factor 11 (GDF11) are attenuated by H. serrata, together with associated downstream signaling factors including phospho‐Smad3 and NADPH oxidase 4 (NOX4). Conclusion H. serrata enhances exercise endurance by upregulating PPARδ and downregulating TGF‐β, myostatin, and GDF11. H. serrata is a potential candidate for the development of functional food to maintain skeletal muscle mass and function.

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Mitochondria Initiate and Regulate Sarcopenia

Cited by 97 publications

References 151 publications

The role of SIRT1 in skeletal muscle function and repair of older mice

The role of SIRT1 in skeletal muscle function and repair of older mice

Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes

Hydrangea serrata Tea Enhances Running Endurance and Skeletal Muscle Mass

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