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Determining the feasibility of characterising cellular senescence in human skeletal muscle and exploring associations with muscle morphology and physical function at different ages: findings from the MASS_Lifecourse Study

Lookup NU author(s): Leena Habiballa, Dr Antoneta Granic, Dr Richard DoddsORCiD, Susan HillmanORCiD, Diana Jurk, Dr Joao Passos, Professor Avan SayerORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2023, The Author(s).Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47–84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = − 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = − 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.


Publication metadata

Author(s): Habiballa L, Hruby A, Granic A, Dodds RM, Hillman SJ, Jurk D, Passos JF, Sayer AA

Publication type: Article

Publication status: Published

Journal: GeroScience

Year: 2023

Volume: 46

Pages: 1141–1158

Online publication date: 11/07/2023

Acceptance date: 05/07/2023

Date deposited: 06/07/2023

ISSN (print): 2509-2715

ISSN (electronic): 2509-2723

Publisher: Springer Science and Business Media Deutschland GmbH

URL: https://doi.org/10.1007/s11357-023-00869-4

DOI: 10.1007/s11357-023-00869-4

PubMed id: 37434081


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Funding

Funder referenceFunder name
Glenn Foundation for Medical Research
NIHR Newcastle BRC
NIH
P01 AG062413
R01 AG068182-01
R01AG068048-01
Ted Nash long life foundation
UG3CA268103-01

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