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Research Paper|Volume 17, Issue 6|pp 1466—1483

Developing a quantitative estimate of muscle age acceleration by a novel phenotypic clock: cross-sectional study in healthy, middle-aged and older adults

Lucia Ventura1,2, Antonella Cano1, Marco Morrone1, Gianluca Martinez1, Anna Boi1, Maria Grazia Catte1, Beniamina Mercante1, Nicola Loi1, Oksana Yurchyshyn3, Giovanni Fiorito4, Giuliana Solinas1, Sara Cruciani1, Donatella Coradduzza1, Margherita Maioli1, Angelo Zinellu1, Ciriaco Carru1, Franca Deriu1,5, Andrea Manca1
  • 1Department of Biomedical Sciences, University of Sassari, Sassari, Italy
  • 2Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
  • 3Ternopil National Medical University, Ternopil, Ukraine
  • 4IRCCS Ospedale Pediatrico Giannina Gaslini, Genova, Italy
  • 5Endocrinology Unit, AOUSS, Sassari, Italy
* Equal contribution
Received: December 10, 2024Accepted: June 2, 2025Published: June 9, 2025

Copyright: © 2025 Ventura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Sarcopenia is a progressive disease characterized by reductions in muscle mass strength and physical performance. Among the initiatives launched to increase awareness, the European Working Group on Sarcopenia in Older People (EWGSOP) is considered the most influential. This cross-sectional study was planned to develop, in healthy middle-aged and older adults, a novel predictor of sarcopenia based on the motor-functional and anthropometric tests derived from EWGSOP2, which were the primary outcome measures.

Participants were tested for body composition, physical performance, blood biomarkers, and risk scores for major healthy issues. Muscle Age Acceleration (MAA) was modelled with Elastic Net regression to extract EWGSOP test mostly contributing to the musculoskeletal ageing trajectory.

Two-hundred-fifteen participants were tested (118 women, 97 men; mean age; 66.0±7.3 years). Muscle Age was correlated with chronological age (r = 0.645; p < 0.001). Parsimonious modelling extracted TUG (β = 2.93; 2.48 - to −3.51), ASMM (β = −2.23; −2.99 to −1.67) and Handgrip (β = −1.12; −1.70 to −0.42) for men, and TUG (β = 2.69; 1.96 to 4.19), Handgrip (β = −1.27; −1.56 to −0.98), and Six-MWT (β = −1.15; −1.71 to −0.53) for women. According to MAA, three trajectories were identified: accelerated agers displayed higher risk for sarcopenia (19%), as compared to normal (9%; p < 0.0001) and decelerated (2%; p < 0.0001), paralleled by significant subclinical alterations of haemato-chemical markers in accelerated agers.

MAA could validly identify accelerated agers with higher risk of sarcopenia, whereas PhenoAge detected subclinical haematochemical alterations. Longitudinal studies are needed to appraise the validity of this newly introduced predictor of sarcopenia and verify if accelerated agers are at higher risk for developing sarcopenia.