A neuromuscular perspective of sarcopenia pathogenesis: deciphering the signaling pathways involved

Moreira‐Pais, Alexandra; Ferreira, Rita; Oliveira, Paula A.; Duarte, José Alberto

doi:10.1007/s11357-021-00510-2

Cited by 28 publications

(21 citation statements)

References 125 publications

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“…With aging, however, this process of NMJ remodeling occurs at a more rapid rate and with a more pronounced severity. resulting in first partial, and then total, denervation of the affected myofiber, ultimately leading to its death, i.e., “sarcopenia” [ 115 , 116 ]. Some but not all of these newly abandoned, or denervated, myofibers will be re-innervated by neighboring motor neurons, although the requisite terminal sprouting is limited with aging [ 117 , 118 ].…”

Section: Effects Of Aging On the Nmjmentioning

confidence: 99%

Adaptive Remodeling of the Neuromuscular Junction with Aging

Deschenes

Flannery

Hawbaker

et al. 2022

Cells

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Aging is associated with gradual degeneration, in mass and function, of the neuromuscular system. This process, referred to as “sarcopenia”, is considered a disease by itself, and it has been linked to a number of other serious maladies such as type II diabetes, osteoporosis, arthritis, cardiovascular disease, and even dementia. While the molecular causes of sarcopenia remain to be fully elucidated, recent findings have implicated the neuromuscular junction (NMJ) as being an important locus in the development and progression of that malady. This synapse, which connects motor neurons to the muscle fibers that they innervate, has been found to degenerate with age, contributing both to senescent-related declines in muscle mass and function. The NMJ also shows plasticity in response to a number of neuromuscular diseases such as amyotrophic lateral sclerosis (ALS) and Lambert-Eaton myasthenic syndrome (LEMS). Here, the structural and functional degradation of the NMJ associated with aging and disease is described, along with the measures that might be taken to effectively mitigate, if not fully prevent, that degeneration.

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Section: Effects Of Aging On the Nmjmentioning

confidence: 99%

Adaptive Remodeling of the Neuromuscular Junction with Aging

Deschenes

Flannery

Hawbaker

et al. 2022

Cells

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“…However, both NfL and CAF concentrations were markedly higher than those of a young reference population analysed in our laboratory ( Figure 3), highlighting that, in older individuals, sarcopenia is associated with NMJ instability 5 and axonal damage 9,10 …”

Section: Discussionmentioning

confidence: 71%

“…Hence, we cannot exclude the possibility that, by testing a larger sample, NfL concentration in sarcopenic elderly would increase significantly over time. In fact, on larger cohorts, NfL blood concentration has been shown to augment with age in neurological disease‐free individuals 9,10 to different rates and up to 4.3% per year, potentially due to motoneuronal loss (especially fast‐twitch fibre innervating motoneurons) 5 . Thus, up to about 10% of the total NfL increment observed in HALE might be explained by the pure ageing process.…”

Section: Discussionmentioning

confidence: 99%

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

Monti

Tagliaferri

Zampieri

et al. 2023

J cachexia sarcopenia muscle

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Background Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. Methods Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. Results At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (À8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. Conclusions The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

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“…Agrin is released by motor neurons ( 19 ). Action potentials can be correctly transmitted from nerve endings to muscle through the agrin-muscle specific kinase (MuSk)-lipoprotein receptor-related protein 4 (Lrp4) signaling pathway, which is essential for maintaining normal neuromuscular function ( 20 ).…”

Section: Neuromuscular Junction Lesionmentioning

confidence: 99%

Sarcopenia: Molecular regulatory network for loss of muscle mass and function

Ding²,

Wu³

et al. 2023

Front. Nutr.

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Skeletal muscle is the foundation of human function and plays a key role in producing exercise, bone protection, and energy metabolism. Sarcopenia is a systemic disease, which is characterized by degenerative changes in skeletal muscle mass, strength, and function. Therefore, sarcopenia often causes weakness, prolonged hospitalization, falls and other adverse consequences that reduce the quality of life, and even lead to death. In recent years, sarcopenia has become the focus of in-depth research. Researchers have suggested some molecular mechanisms for sarcopenia according to different muscle physiology. These mechanisms cover neuromuscular junction lesion, imbalance of protein synthesis and breakdown, satellite cells dysfunction, etc. We summarize the latest research progress on the molecular mechanism of sarcopenia in this review in order to provide new ideas for future researchers to find valuable therapeutic targets and develop relevant prevention strategies.

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A neuromuscular perspective of sarcopenia pathogenesis: deciphering the signaling pathways involved

Cited by 28 publications

References 125 publications

Adaptive Remodeling of the Neuromuscular Junction with Aging

Adaptive Remodeling of the Neuromuscular Junction with Aging

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

Sarcopenia: Molecular regulatory network for loss of muscle mass and function

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