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Lookup NU author(s): Dr Louise ReynardORCiD, Dr Daryl Shanley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.Age is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model. We developed a highly accurate epigenetic clock, MskAge, that is specific to tissues and cells of the musculoskeletal system. MskAge was built using a penalised genetic algorithm islands model that addresses multi-tissue clock bias. The final model was trained on the transformed principal components of CpGs selected by the genetic algorithm. We show that MskAge tracks epigenetic ageing ex vivo and in vitro. Epigenetic age estimates are rejuvenated with cellular reprogramming and are accelerated at a rate of 0.45 years per population doubling. MskAge explains more variance associated with in vitro ageing of fibroblasts than the purpose-developed skin and blood clock. The precision of MskAge and its ability to capture perturbations in biological ageing make it a promising research tool for musculoskeletal and ageing biologists.
Author(s): Green DC, Reynard LN, Henstock JR, Reppe S, Gautvik K, Peffers MJ, Shanley DP, Clegg PD, Canty-Laird EG
Publication type: Article
Publication status: Published
Journal: Aging Cell
Year: 2025
Pages: epub ahead of print
Online publication date: 19/06/2025
Acceptance date: 02/06/2025
Date deposited: 09/07/2025
ISSN (print): 1474-9718
ISSN (electronic): 1474-9726
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/acel.70149
DOI: 10.1111/acel.70149
Data Access Statement: The data are available from the corresponding author upon reasonable request.
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