Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality
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Abstract
Associations of biological aging with the development and mortality of cardiometabolic multimorbidity (CMM) remain unclear. Here we conducted a multistate analysis in 341,159 adults of the UK Biobank. CMM was defined as the coexistence of two or three cardiometabolic diseases (CMDs), including type 2 diabetes, ischemic heart disease and stroke. Biological aging was measured using the Klemera-Doubal Method Biological Age and PhenoAge algorithms. Over a median follow-up of 8.84 years, biologically older participants demonstrated robust higher risks from first CMD to CMM and then to death. In particular, adjusted hazard ratios for first CMD to CMM and for CMM to death were 1.15 (95% confidence interval (CI): 1.12, 1.19) and 1.26 (95% CI: 1.17, 1.35) per 1 s.d. increase in PhenoAge acceleration, respectively. Compared with frailty, Framingham Risk Score and Systematic Coronary Risk Evaluation 2 (SCORE2), biological aging measures yielded consistent substantial associations with CMM development. Accelerated biological aging may help identify individuals with CMM risks, potentially enabling early intervention and subclinical prevention.
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Accelerated telomere shortening is proposed to arise from oxidative stress and chronic inflammation, both of which are strongly involved in cardiometabolic disease.
“In this context, accelerative TL shortening is suggested to be a result from oxidative stress and chronic inflammation, both of which are strongly implicated in the development of cardiometabolic disease (Jiang et al., 2024; Sverdlov et al., 2016).”
From Telomere trajectories from early adolescence to adulthood following early institutionalization: Protective effects of foster care in the Bucharest Early Intervention Project (2026) · cites this paper as Jiang et al., 2024
The Discussion (page unavailable) links telomere shortening in type 2 diabetes to pathological changes that could contribute to cardiometabolic multimorbidity. It does not propose that oxidative stress or chronic inflammation causes accelerated telomere shortening, or discuss those mechanisms in the cited passage. (LLM, conf=0.82)
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- Authors
- Jiang, M., Tian, S., Liu, S., Wang, Y., Guo, X., Huang, T., Lin, X., Belsky, D. W., Baccarelli, A. A., & Gao, X.
- Affiliations
- Peking University (CN)
- Harvard University (US)
- Columbia University (US)
- Corresponding author
- Gao, Xu
- ORCID
- Venue
- Nature Cardiovascular Research
- Published
- 2024-03-01
- Volume
- 3
- Issue
- 3
- Pages
- 332-342
- ISSN
- 2731-0590 (ISSN-L)
- PMC
- PMC13265155
- OpenAlex
- W4392385114
- Cited by
- 117
- References
- 41
- Citations by year
- 2026: 48 · 2025: 58 · 2024: 11
- FWCI
- 35.70
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-06-27)
- Open access
- green
- dx.doi.org
- Licence
- Locations
- Nature Cardiovascular Research (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Chinese Center for Disease Control and Prevention (2022-CKL-03)
- Peking University (BMU2021YJ044)
- Centers for Disease Control and Prevention
- National Key Research and Development Program of China (2022YFC3702704)
- National Heart, Lung, and Blood Institute (R01HL163560)
- National Human Genome Research Institute (U01HG012064)
- Topics
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- biological aging, cardiometabolic multimorbidity, PhenoAge, accelerated aging, type 2 diabetes, ischemic heart disease, stroke, mortality, frailty, cardiovascular risk prediction, multi-state models
- MeSH terms
- Multimorbidity, Cardiometabolic Risk Factors, Adult, Age Factors, Aged, Aging, Diabetes Mellitus, Type 2, Female, United Kingdom, Humans, Male, Middle Aged, Prognosis, Risk Factors, Time Factors, Myocardial Ischemia, Risk Assessment, Stroke
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