Higher biological age acceleration was associated with increased risks of incident CVD and premature mortality, with more pronounced associations observed in males.
Key Findings
Results
Biological age acceleration measured by KDM-BA was associated with increased risk of incident CVD.
Study included 122,133 participants free of CVD at baseline from the UK Biobank, recruited 2006–2010 and followed until Dec 20, 2022
Mean (SD) age was 56.0 (8.1) years; 65,442 (53.6%) were women
Compared with the lowest quartile of KDM-BA acceleration, the HR for incident CVD in quartile 4 was 1.32 (95% CI 1.27–1.37)
24,281 incident CVD cases were reported over the follow-up period
Restricted cubic splines showed progressively increasing risks of incident CVD with higher BA acceleration
Results
Biological age acceleration measured by KDM-BA was associated with increased risk of premature mortality.
Premature mortality was defined as death before age 70
3,614 premature deaths were reported over the follow-up period
Compared with the lowest quartile of KDM-BA acceleration, the HR for premature mortality in quartile 4 was 1.10 (95% CI 1.05–1.21)
Restricted cubic splines showed progressively increasing risks of premature mortality with higher BA acceleration
Results
Biological age acceleration measured by PhenoAge was associated with increased risks of both incident CVD and premature mortality.
For PhenoAge acceleration, the HR for incident CVD in quartile 4 compared with quartile 1 was 1.23 (95% CI 1.19–1.28)
For PhenoAge acceleration, the HR for premature mortality in quartile 4 compared with quartile 1 was 1.21 (95% CI 1.10–1.33)
Both KDM-BA and PhenoAge algorithms were used to calculate biological age from clinical biomarkers
Biological age acceleration was defined as the residual from regressing BA on chronological age
Results
The associations between biological age acceleration and CVD and premature mortality were more pronounced in male participants.
Sex differences in the associations were statistically significant (P-interaction < 0.05)
The interaction analysis was performed for both KDM-BA and PhenoAge acceleration measures
The study included 65,442 women (53.6%) and the remainder were men
Authors concluded that sex-specific strategies may be needed to improve health outcomes
Methods
The study used a prospective cohort design with multivariable-adjusted Cox proportional hazards models to assess associations between biological age acceleration and health outcomes.
Participants were aged 39 to 71 years at recruitment from the UK Biobank study
Recruitment occurred between 2006 and 2010, with follow-up until December 20, 2022
Incident CVD and premature mortality were identified using ICD-9 and ICD-10 codes
Hazard ratios and 95% confidence intervals were estimated across biological age acceleration quartiles
Biological age was calculated using both the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms derived from clinical biomarkers
What This Means
This research suggests that people whose bodies age faster biologically than expected for their actual age are at greater risk of developing heart disease and dying before age 70. The study followed over 122,000 middle-aged adults from the UK Biobank for up to about 16 years. It measured 'biological age' using two different scientific methods based on clinical lab results, and found that people in the highest quarter of biological age acceleration — meaning their bodies appeared biologically older than their birth age would predict — had roughly 23–32% higher risk of developing cardiovascular disease and up to 21% higher risk of premature death compared to those in the lowest quarter.
One notable finding was that these risks were stronger in men than in women, with statistically significant differences between sexes. This suggests that biological aging may affect men's cardiovascular health and longevity more sharply, and that health interventions might need to be tailored differently by sex. The relationship between biological age acceleration and these health risks was also dose-dependent — the faster the biological aging, the higher the risk — rather than showing a simple threshold effect.
This research suggests that measuring biological age acceleration using routine clinical biomarkers could be a useful tool for identifying people at higher risk of heart disease and early death. Because biological aging may be influenced by lifestyle and other modifiable factors, the authors propose that biological age acceleration could serve as a target for interventions aimed at reducing cardiovascular risk, particularly with attention to differences between men and women.
Yang Y, Yin S, Li D, Wan H, He J, Yuan L, et al.. (2026). Association of biological age acceleration with cardiovascular disease and premature mortality: a population-based prospective cohort study.. Frontiers in public health. https://doi.org/10.3389/fpubh.2026.1816971