This study examined whether having an accelerated biological age in midlife is associated with greater long-term risk of cardiovascular disease, dementia, and all-cause mortality. Researchers used data from the Framingham Offspring Study cohorts and restricted analyses to participants with the clinical biomarker data needed to estimate biological age. The report notes that biological age reflects cellular or physiological aging and may differ from chronological age.
Investigators calculated an estimated biological age using available clinical biomarkers. They included measures such as total blood cholesterol, blood glucose, and Mini‑Mental State Exam scores among other biomarkers, and adjusted for covariates including diabetes, antihypertensive medication use, and smoking status. The team evaluated three principal outcomes: incident cardiovascular disease, incident dementia, and all‑cause mortality.
Median follow-up times were long: 26 years for dementia and mortality analyses and 23 years for cardiovascular disease analyses. During follow-up the cohort experienced 713 cardiovascular events, 265 dementia diagnoses, and 1,105 deaths.
Participants were classified into three biological‑age categories: accelerated, concordant, or decelerated. Concordant biological age denotes that estimated biological age roughly matched chronological age. Among those with accelerated biological age, the average biological age exceeded chronological age by about 4 years for men and 2.5 years for women. Most participants were middle‑aged and fell into the concordant category.
Compared with participants in the decelerated biological‑age group, those with accelerated biological age had higher risks of cardiovascular disease and death. Specifically, accelerated biological age was associated with roughly a 1.6‑fold greater cardiovascular disease risk for men and a 1.8‑fold greater risk for women. For all‑cause mortality, accelerated biological age corresponded to about a 2‑fold higher risk for both men and women relative to the decelerated group.
These associations indicate that estimated biological age tracked long‑term cardiometabolic and survival outcomes in this sample.
The relationship between accelerated biological age and dementia differed by sex. For men, accelerated biological age did not show a statistically significant increase in dementia risk. For women, accelerated biological age was associated with an increased dementia risk. Sensitivity analyses further indicated that women with accelerated biological age — and, to a lesser extent, those with concordant biological age — had higher dementia risk than women with decelerated biological age.
The authors and commentators emphasized several important limitations. The study is observational and cannot establish causation; residual confounding is possible. Biological age in this study is an estimated, proxy measure derived from a subset of clinical biomarkers. The authors acknowledge lacking data on additional biomarkers that could be relevant to the aging process, and they note there is no universally accepted standard method to calculate biological age, which limits comparability across studies.
Generalisability is also limited because many Framingham Offspring participants were white and of European descent. The report cites these factors as constraining how broadly the results can be applied.
External experts commented on the findings and their practical meaning. One cardiologist pointed out that adding biological age to a model already containing chronological age and established risk factors (smoking, blood pressure, diabetes, lipids, BMI) produced only a marginal improvement in prediction — a change in the c‑statistic on the order of 0.01. This suggests biological age tracks risk but may not add substantial independent discriminative power beyond standard risk factors.
Another clinician noted that biological age could be useful as a conversational or motivational framing tool in clinical care (for example, communicating that a patient’s body appears older than their years) but cautioned there is currently no specific therapy for accelerated aging itself; management targets remain the established modifiable risk factors.
The study does not immediately mandate changes to clinical practice. Authors and outside experts suggest potential roles for biological age estimation in identifying individuals at higher risk of adverse outcomes not captured by single biomarkers, and as a way to foster patient engagement on risk‑factor modification. However, before clinical implementation, research is needed to: standardize and validate methods to calculate biological age; investigate which biomarkers and exposures most meaningfully reflect biological aging; examine contributors to accelerated biological aging (for example, socioeconomic factors, education, substance use, environmental exposures); and clarify the mechanisms behind the observed sex difference in dementia risk.
In this long‑term observational analysis of Framingham Offspring participants, accelerated estimated biological age in midlife was associated with higher risks of cardiovascular disease and mortality for both sexes, and with increased dementia risk in women only. The findings highlight potential value in studying biological age as an integrative risk signal but also underline methodological limitations, limited added predictive discrimination beyond established risk factors, and the need for further research before routine clinical adoption.