Sarcopenia – Molecular mechanisms and open questions

Wiedmer, Petra; Jung, Tobias; Castro, José Pedro; Pomatto, Laura C.D.; Sun, Patrick Y.; Davies, Kelvin J.A.; Grune, Tilman

doi:10.1016/j.arr.2020.101200

Cited by 190 publications

(101 citation statements)

References 165 publications

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“…The levels of GH and IGF-1 show a downward trend with age, leading to Decrease in muscle mass and increase in fat mass [69]. In patients with type 2 diabetes, the GH/IGF-1 axis shows an increase in GH and a decrease in IGF-1 [70]. And in this metaanalysis, age, HbA1c, osteoporosis, BMI and metformin were con rmed to be associated with sarcopenia, which was consistent to previous researches.…”

Section: (5)supporting

confidence: 90%

The Prevalence and Risk Factors of Sarcopenia in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Liu

2021

Preprint

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BackgroundSarcopenia was a frequent chronic complication in patients with type 2 diabetes mellitus (T2DM), and previous evidence showed conflicting results regarding the prevalence and risk factors of sarcopenia in T2DM. In the current study, we aimed at systematically exploring the prevalence and risk factors of sarcopenia in patients with T2DM. MethodsPubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched to identify observational studies which investigated the prevalence and risk factors of sarcopenia in patients with T2DM. The quality of individual included studies was evaluated using The Newcastle–Ottawa scale. Pooled effects regarding prevalence and associated factors were calculated using random-effects models. The potential publication bias was assessed via funnel plot and Egger test. ResultsTwenty-eight studies involving 16800 patients were included in our meta-analysis. The pooled prevalence of sarcopenia in patients with T2DM was 18% (95% CI, 0.15-0.22; I2=97.4%). The pooled results showed that elder age (OR, 4.73; 95% CI, 4.30-5.19; I2=85.6%), male gender, chronic hyperglycemia (higher HbA1c) (OR, 1.16; 95% CI,1.05-2.47; I2=99.2%) and osteoporosis (OR, 1.16; 95% CI,1.05-2.47; I2=99.2%) was predictors for sarcopenia, whereas patients with lower BMI (OR, 1.16; 95% CI,1.05-2.47; I2=99.2%) and metformin administrations (OR, 1.16; 95% CI,1.05-2.47; I2=99.2%) were not prone to get sarcopenia. The funnel plot and statistical tests showed no obvious publication bias. ConclusionsSarcopenia was frequent in T2DM patients. Elder age, male gender and chronic hyperglycemia, Osteoporosis were significant risk factors for Sarcopenia. Lower BMI and metformin administrations were associated with lower risk of sarcopenia.

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Section: (5)supporting

confidence: 90%

The Prevalence and Risk Factors of Sarcopenia in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Liu

2021

Preprint

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“…During aging, the infiltration of fat, connective tissue and scar tissue into a muscle can reduce the overall cross-sectional area devoted to contractile units while altering structural parameters of the tissue, and combined with other macro level alterations such as tendon stiffening, may reduce power and strength at the whole muscle level (Wu, 2020;Rahemi, 2015). In addition, at the cellular level, there are many deleterious changes with aging that can affect contractile velocity, power production and force generation, such as: posttranslation modifications to key contractile proteins that might inhibit or slow down cross-bridge cycling or limit the number of bound myosin heads at any given moment (such as glycosylation of actin or myosin heavy chain), a shift in the myosin light chains to slower isoforms, fiber-type shift to slower less powerful myofiber types and increased hybrid fibers, enhanced denervation of type 2 motor units with reduced rates of re-innervation, cell signaling abnormalities potentially resulting from such divergent sources as enhanced global inflammation and reduced hormonal signaling, autophagy dysregulation resulting in cellular "junk" accumulation including reduced mitophagy rates leading to a greater number of dysfunction mitochondria leaking enhanced protein/DNA/RNA damaging reactive oxygen species (ROS), and many others (Prochiewicz, 2007;Wiedmer, 2021).…”

Section: Physical Function Declines With Agingmentioning

confidence: 99%

Skeletal Muscle Transcriptome Alterations Related to Physical Function Decline in Older Mice

Graber

Maroto

Thompson³

et al. 2021

Preprint

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One inevitable consequence of aging is the gradual deterioration of physical function and exercise capacity, driven in part by the adverse effect of age on muscle tissue. Our primary purpose was to determine the relationship between patterns of gene expression in skeletal muscle and this loss of physical function. We hypothesized that some genes changing expression with age would correlate with functional decline, or conversely with preservation of function. Male C57BL/6 mice (6-months old, 6m, 24-months, 24m, and 28+-months, 28m; all n=8) were tested for physical ability using a comprehensive functional assessment battery (CFAB). CFAB is a composite scoring system comprised of five functional tests: rotarod (overall motor function), grip strength (fore-limb strength), inverted cling (4-limb strength/endurance), voluntary wheel running (activity rate/volitional exercise), and treadmill (endurance). We then extracted total RNA from the tibialis anterior muscle, analyzed with Next Generation Sequencing RNAseq to determine differential gene expression during aging, and compared these changes to physical function. Aging resulted in gene expression differences >│1.0│ log2 fold change (multiple comparison adjusted p<0.05) in 219 genes in the 24m and in 6587 genes in the 28m. Linear regression with CFAB determined 253 differentially expressed genes strongly associated (R>0.70) with functional status in the 28m, and 22 genes in the 24m. We conclude that specific age-related transcriptomic changes are associated with declines in physical function, providing mechanistic clues. Future work will establish the underlying cellular mechanisms and the physiological relevance of these genes to age-related loss of physical function.

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“…In rodents and worms (but also in humans), exercise and a range of natural compounds alleviate the effect of muscle aging [21]. Reducing the insulin/IGF1 receptor pathway, well known to promote longevity, also improves sarcopenia [22]. In animal models, mitochondrial dysfunction (fragmentation and/or decreased number) may also contribute to the onset of sarcopenia: in rodents, there is an age-dependent reduction in mitochondrial mass associated with a change in morphology; in nematodes, there is an agedependent fragmentation of mitochondria that precedes sarcomeric disorganization [23].…”

Section: Introductionmentioning

confidence: 99%

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

Mancinelli

Checcaglini

Coscia

et al. 2021

IJMS

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In the last decade, clear evidence has emerged that the cellular components of skeletal muscle are important sites for the release of proteins and peptides called “myokines”, suggesting that skeletal muscle plays the role of a secretory organ. After their secretion by muscles, these factors serve many biological functions, including the exertion of complex autocrine, paracrine and/or endocrine effects. In sum, myokines affect complex multi-organ processes, such as skeletal muscle trophism, metabolism, angiogenesis and immunological response to different physiological (physical activity, aging, etc.) or pathological states (cachexia, dysmetabolic conditions, chronic inflammation, etc.). The aim of this review is to describe in detail a number of myokines that are, to varying degrees, involved in skeletal muscle aging processes and belong to the group of proteins present in the functional environment surrounding the muscle cell known as the “Niche”. The particular myokines described are those that, acting both from within the cell and in an autocrine manner, have a defined relationship with the modulation of oxidative stress in muscle cells (mature or stem) involved in the regulatory (metabolic or regenerative) processes of muscle aging. Myostatin, IGF-1, NGF, S100 and irisin are examples of specific myokines that have peculiar features in their mechanisms of action. In particular, the potential role of one of the most recently characterized myokines—irisin, directly linked to an active lifestyle—in reducing if not reversing senescence-induced oxidative damage is discussed in terms of its possible application as an agent able to counteract the deleterious effects of muscle aging.

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Sarcopenia – Molecular mechanisms and open questions

Cited by 190 publications

References 165 publications

The Prevalence and Risk Factors of Sarcopenia in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

The Prevalence and Risk Factors of Sarcopenia in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Skeletal Muscle Transcriptome Alterations Related to Physical Function Decline in Older Mice

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

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