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. 2024 Dec;43(12):3615-3623.
doi: 10.1007/s10067-024-07167-0. Epub 2024 Oct 5.

Associations of accelerated biological aging and metabolic heterogeneity of obesity with rheumatoid arthritis: a prospective cohort study

Chan-Na Zhao  1   2 , Ling-Qiong Jiang  3 , Harry Asena Musonye  1   2 , Shi-Yin Meng  1   2 , Yi-Sheng He  1   2 , Peng Wang  4 , Jing Ni  5   6 , Hai-Feng Pan  7   8
Affiliations

Associations of accelerated biological aging and metabolic heterogeneity of obesity with rheumatoid arthritis: a prospective cohort study

Chan-Na Zhao et al. Clin Rheumatol. 2024 Dec.

Abstract

Objective: To evaluate the associations between biological aging, metabolic heterogeneity of obesity, and rheumatoid arthritis (RA).

Methods: This prospective cohort study analyzed 268,184 individuals from the UK Biobank. Biological age was estimated using phenotypic age (PhenoAge), Klemera-Doubal methods (KDM-BA), and telomere length. We calculated KDM-BA acceleration and PhenoAge acceleration after subtracting the effect of chronological age by regression residual. The metabolic heterogeneity of obesity can be evaluated by four BMI metabolic phenotypes, namely metabolically unhealthy normal weight (MUNW), metabolically healthy normal weight (MHNW), metabolically unhealthy overweight/obesity (MUOO), and metabolically healthy overweight/obesity (MHOO). Cox models were employed to estimate the associations between biological aging, metabolic heterogeneity of obesity, and RA risk.

Results: A total of 2842 patients experienced RA during a mean follow-up time of 12.21 years. A standard deviation (SD) increase in KDM-BA acceleration and PhenoAge acceleration was associated with an increased risk of RA by 13% (hazard ratio = 1.13; 95% CI, 1.09-1.17) and 39% (HR = 1.39; 95% CI, 1.34-1.44), respectively. A SD increase in telomere length was associated with a reduced risk of RA by 5% (HR = 0.95; 95% CI, 0.91-0.98). Compared to the MHNW group, the MUOO group was associated with a 51% increase in the risk of incident RA. In the joint effect analysis, compared to the MHNW + KDM-BA younger subgroup, the HR (95% CI) for RA was 1.68 (1.48, 1.90) in the MUOO + KDM-BA older subgroup.

Conclusion: Accelerated biological aging may heighten the susceptibility to RA, particularly in individuals with obesity or metabolic dysfunction. Key Points •Accelerated biological aging increases the risk of developing RA. •Overweight/obese people with a healthy metabolism have a higher risk of RA than those with normal weight and healthy metabolism. •The BMI metabolic phenotype has a strong modifying effect on the association between KDM-BA/PhenoAge and RA risk.

Keywords: Biological aging; Metabolic status; Obesity; Rheumatoid arthritis.

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Conflict of interest statement

Declarations. Ethics approval: All individuals involved provided written approval, and the North West-Haydock Research Ethics Committee approved the study (16/NW/0274). Disclosures: None.

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