MskAge—An Epigenetic Biomarker of Musculoskeletal Age Derived From a Genetic Algorithm Islands Model

Green, DC, Reynard, LN, Henstock, JR, Reppe, S ORCID: 0000-0002-4330-5379, Gautvik, K, Peffers, MJ ORCID: 0000-0001-6979-0440, Shanley, DP, Clegg, PD and Canty-Laird, EG ORCID: 0000-0001-5041-1316 (2025) MskAge—An Epigenetic Biomarker of Musculoskeletal Age Derived From a Genetic Algorithm Islands Model Aging Cell, 24 (9). e70149-. ISSN 1474-9718, 1474-9726

Access the full-text of this item by clicking on the Open Access link.

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	ageing, biomarker, epigenetics, genetic algorithm, musculoskeletal system
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	30 Jun 2025 10:14
Last Modified:	28 Feb 2026 17:27
DOI:	10.1111/acel.70149
Open Access URL:	https://doi.org/10.1111/acel.70149
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3193375
Disclaimer:	The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate.