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. 2025 Sep;43(5):573-584.
doi: 10.1007/s00774-025-01630-x. Epub 2025 Aug 18.

Unhealthy lifestyles accelerated aging and consequential musculoskeletal morbidity

Hao-Long Zhou  1 , Jiao-Jun Liang  2 , Jonathan K L Mak  3 , Zhang-Bo Cui  1 , Dan-Yang Ling  1 , Sara Hägg  3 , Qi Wang  4
Affiliations

Unhealthy lifestyles accelerated aging and consequential musculoskeletal morbidity

Hao-Long Zhou et al. J Bone Miner Metab. 2025 Sep.

Abstract

Introduction: Few studies assessed comprehensive effects of composite unhealthy lifestyles on aging and musculoskeletal health. This study aimed to address such issues with the UK Biobank datasets.

Materials and methods: An unhealthy lifestyle score (UHLS) was constructed based on 9 lifestyle behaviors. Aging indicators were calculated from 18 clinical traits. General linear and Cox proportional hazards regression models were used to analyze associations between UHLS, aging, and musculoskeletal morbidity. Mendelian randomization (MR) analysis was performed for causal relationship exploration.

Results: Among 396,037 participants, 54.5% and 3.3% of them were designated to the low (scored 0-2) and high UHLS (scored 6-9) groups, respectively. Increasing UHLS was associated with elevated aging acceleration (AA) based on biological age (0.343 per unit; 95% CI: 0.331, 0.355) and phenotypic age (AA_PA) (0.408 per unit; 95% CI: 0.394, 0.422), and higher morbidity of low grip strength (HR = 1.025; 95% CI: 1.001, 1.050), slow walking pace (HR = 1.134; 95% CI: 1.074, 1.198), osteoporosis (HR = 1.077; 95% CI: 1.063, 1.091), fracture (HR = 1.059; 95% CI: 1.048, 1.069) and osteoarthritis (HR = 1.036; 95% CI: 1.030, 1.042). Unhealthy lifestyles in conjunction with AA jointly increased musculoskeletal morbidity. Besides, AA mediated UHLS effects on slow walking pace, osteoporosis and fracture, with mediating proportion of 4.85%-12.79%. MR analyses revealed causal relationships between UHLS and low grip strength, osteoarthritis, and reduced femoral neck bone mineral density. In addition, AA_PA suggestively mediated the UHLS-osteoarthritis association.

Conclusions: Composite unhealthy lifestyles accelerate aging and impair musculoskeletal health. Both mediating and joint effects of AA showed unhealthy lifestyle-associated musculoskeletal morbidity.

Keywords: Aging acceleration; Composite unhealthy lifestyle; Mediation; Musculoskeletal disorders.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The UKB was approved by the North West Multi-Center Research Ethics Committee, and all the participant provided informed consent. Clinical Trial Number: Not applicable. Conflict of interest: Hao-long Zhou, Jiao-jun Liang, Jonathan K L Mak, Zhang-bo Cui, Dan-yang Ling, Sara Hägg, and Qi Wang have no potential conflict of interest.

Comment in

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