Human neuromuscular aging: Sex differences revealed at the myocellular level

Roberts, Brandon M.; Lavin, Kaleen M.; Many, Gina M.; Thalacker‐Mercer, Anna; Merritt, Edward; Bickel, C. Scott; Mayhew, David L.; Tuggle, S. Craig; Cross, James M.; Kosek, David J.; Petrella, John K.; Brown, Cynthia J.; Hunter, Gary R.; Windham, Samuel T.; Allman, Richard M.; Bamman, Marcas M.

doi:10.1016/j.exger.2018.02.023

Cited by 69 publications

(66 citation statements)

References 49 publications

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“…; Roberts et al . ), and Roberts et al . have previously commented that in human muscle from individuals below the age of 75 years, the abundance of MHC co‐expressing fibres is typically low (Roberts et al .…”

Section: Discussionmentioning

confidence: 89%

“…have previously commented that in human muscle from individuals below the age of 75 years, the abundance of MHC co‐expressing fibres is typically low (Roberts et al . ). To the best of our knowledge, there is only one study in very old frail individuals (75% were women), and interestingly, when MHC composition was assessed in single fibres by SDS PAGE almost 52% of all muscle fibres were seen to be co‐expressing multiple MHC isoforms, with the most abundant fibres co‐expressing MHC I/IIa (28%) and MHCIIa/IIx (22%) (Andersen et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Roberts et al . ) reported that the age‐related increase in fibre type grouping is driven by a higher number of myofibres per group (myofibre group size). This has been suggested to be indicative of a larger motor unit, and one which retains the capacity of successful reinnervation to promote maintenance of muscle mass (Piasecki et al .…”

Section: Discussionmentioning

confidence: 99%

“…This corresponded to fibres with a size ࣘ1441 µm 2 . As the ratio of type IIa to type I fibre cross-sectional area (CSA) is reduced with ageing (Roberts et al 2018), we used this measure as an index of the degree to which a given individual had been impacted by ageing (i.e. a greater reduction in type IIa/I size ratio was interpreted as a greater ageing impact).…”

Section: Image Acquisition and Analysismentioning

confidence: 99%

“…[Colour figure can be viewed at wileyonlinelibrary.com] J Physiol 597.19 that have assessed sex-dependent changes in fibre type portion and found that elderly women (63-72 years of age) have 6-10% greater abundance of type I fibres and 8-14% lower abundance of type IIx fibres compared to men (Aniansson et al 1981;Petrella et al 2006;Roberts et al 2018), and Roberts et al have previously commented that in human muscle from individuals below the age of 75 years, the abundance of MHC co-expressing fibres is typically low (Roberts et al 2018). To the best of our knowledge, there is only one study in very old frail individuals (75% were women), and interestingly, when MHC composition was assessed in single fibres by SDS PAGE almost 52% of all muscle fibres were seen to be co-expressing multiple MHC isoforms, with the most abundant fibres co-expressing MHC I/IIa (28%) and MHCIIa/IIx (22%) (Andersen et al 1999).…”

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

confidence: 99%

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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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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Image Acquisition and Analysismentioning

confidence: 99%

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

confidence: 99%

See 3 more Smart Citations

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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State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions

Lavin

Coen

Baptista

et al. 2022

Comprehensive Physiology

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Differentially co‐expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease

Chiles,

Wilson,

Tindal

et al. 2024

J cachexia sarcopenia muscle

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BackgroundSkeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.MethodsForty‐six participants with COPD were assessed for body composition, strength, endurance and pulmonary function. Skeletal muscle biopsies from the vastus lateralis were assayed for fibre‐type distribution and cross‐sectional area via immunofluorescence microscopy and RNA‐sequenced to generate transcriptome‐wide gene expression data. Sex‐stratified k‐means clustering of type I and IIx/IIax fibre proportions was used to define abnormal myofibre proportion in participants with COPD and contrasted with previously defined criteria. Single transcripts and weighted co‐expression network analysis modules were tested for correlation with the abnormal myofibre proportion phenotype.ResultsAbnormal myofibre proportion was defined in males with COPD (n = 29) as <18% type I and/or >22% type IIx/IIax fibres and in females with COPD (n = 17) as <36% type I and/or >12% type IIx/IIax fibres. Half of the participants with COPD were classified as having an abnormal myofibre proportion. Participants with COPD and an abnormal myofibre proportion had lower median handgrip strength (26.1 vs. 34.0 kg, P = 0.022), 6‐min walk distance (300 vs. 353 m, P = 0.039) and forced expiratory volume in 1 s‐to‐forced vital capacity ratio (0.42 vs. 0.48, P = 0.041) compared with participants with COPD and normal myofibre proportions. Twenty‐nine transcripts were associated with abnormal myofibre proportions in participants with COPD, with the upregulated NEB, TPM1 and TPM2 genes having the largest fold differences. Co‐expression network analysis revealed that two transcript modules were significantly positively associated with the presence of abnormal myofibre proportions. One of these co‐expression modules contained genes classically associated with muscle atrophy, as well as transcripts associated with both type I and type II myofibres, and was enriched for genetic loci associated with bone mineral density.ConclusionsOur findings indicate that there are significant transcriptional alterations associated with abnormal myofibre proportions in participants with COPD. Transcripts canonically associated with both type I and type IIa fibres were enriched in a co‐expression network associated with abnormal myofibre proportion, suggesting altered transcriptional regulation across multiple fibre types.

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Human neuromuscular aging: Sex differences revealed at the myocellular level

Cited by 69 publications

References 49 publications

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

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

State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions

Differentially co‐expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease

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