TY - JOUR
T1 - Determining the feasibility of characterising cellular senescence in human skeletal muscle and exploring associations with muscle morphology and physical function at different ages
T2 - findings from the MASS_Lifecourse Study
AU - Habiballa, Leena
AU - Hruby, Adam
AU - Granic, Antoneta
AU - Dodds, Richard M.
AU - Hillman, Susan J.
AU - Jurk, Diana
AU - Passos, João F.
AU - Sayer, Avan A.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2024/2
Y1 - 2024/2
N2 - 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.
AB - 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.
KW - Cellular senescence
KW - Human skeletal muscle ageing
KW - Muscle morphology
KW - Physical function
KW - Sarcopenia
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U2 - 10.1007/s11357-023-00869-4
DO - 10.1007/s11357-023-00869-4
M3 - Article
C2 - 37434081
AN - SCOPUS:85164484986
SN - 2509-2715
VL - 46
SP - 1141
EP - 1158
JO - GeroScience
JF - GeroScience
IS - 1
ER -