Summary: New research indicates that healthy lifestyle choices can lower the risk of stroke, dementia, and late-life depression, even in people whose cells show signs of accelerated biological aging. Telomeres—protective DNA caps at the ends of chromosomes—shorten naturally with age and in response to environmental stressors, and shorter telomeres have been associated with greater vulnerability to age-related brain conditions.
Analyzing data from more than 356,000 participants, researchers found that people with shorter leukocyte telomere length (LTL) who maintained healthier behaviors did not have a higher risk of these brain diseases compared with peers who had longer telomeres. These results underscore the potential of lifestyle measures to protect brain health despite biomarkers of cellular aging.
Key Facts:
- Telomere risk: Shorter telomeres are associated with increased incidence of stroke, dementia, and late-life depression.
- Lifestyle buffer: A high Brain Care Score (BCS), reflecting good sleep, healthy diet, physical activity, and low alcohol use, may offset the risks linked to telomere shortening.
- Actionable insight: People who show biological markers of aging can still reduce their risk by improving modifiable factors.
Source: Mass General
Researchers from Mass General Brigham examined how leukocyte telomere length relates to the risk of age-related brain diseases, and whether lifestyle and clinical risk factors modify that relationship.
Their analysis suggests that healthier lifestyles may mitigate the risk associated with shorter telomeres. The study is published in Neurology.
“Reducing risk factors like weight and alcohol consumption as well as getting more sleep and exercise can all help reverse the risk of age-related brain diseases, even for people who are already showing signs of biological aging,” said lead author Tamara Kimball, MD, from the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital. “In short, it is never too late to start taking better care of your brain.”
Stroke, dementia, and late-life depression become more common with advancing age. Telomeres—protective caps on chromosomes—also shorten with age and when exposed to adverse environmental conditions such as chronic stress or pollution, which can increase vulnerability to DNA damage and disease.
The investigators aimed to determine whether LTL is directly causal for these brain conditions or primarily a predictive marker, and to assess whether modifiable risk factors influence that relationship.
The team analyzed 356,173 participants from the UK Biobank, using leukocyte telomere length measurements together with the McCance Brain Care Score (BCS). The BCS combines clinical measures—blood pressure, blood sugar, cholesterol—with lifestyle and social-emotional factors to create an overall profile of brain health risk.
Results showed that participants with both shorter LTL and lower BCS—indicating less optimal lifestyle and clinical risk profiles—faced higher risks of stroke, dementia, and late-life depression. Importantly, participants with shorter telomeres but higher BCSs, reflecting healthier choices, did not show a significant increase in risk for these outcomes. This pattern suggests that favorable modifiable factors can blunt the association between telomere shortening and disease.
The study does have limitations. LTL was measured only once at the baseline visit, so researchers could not track telomere shortening over time. The cohort was predominantly of European ancestry, which limits the ability to generalize findings across diverse populations. Despite these constraints, the results support the idea that addressing modifiable risk factors may reduce the negative effects of shorter telomeres on brain health and motivate future trials to test lifestyle interventions.
Authorship: In addition to Tamara Kimball, authors from Mass General Brigham include Savvina Prapiadou, Reinier WP Tack, Benjamin YQ Tan, Jasper R. Senff, Chrisna Kourkoulis, Sanjula D. Singh, Jonathan Rosand, and Christopher D. Anderson.
Disclosures: None.
Funding: This work was supported in part by the National Institutes of Health (T32 Fellowship NS100663-06A1, R01NS103924, and U01NS069673), the American Heart Association (18SFRN34250007 and 21SFRN812095), and the MGH McCance Center for Brain Health.
About this brain aging and genetics research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original Research: Closed access. “Association of Leukocyte Telomere Length with Stroke, Dementia, and Late-Life Depression: The Role of Modifiable Risk Factors” by Tamara Kimball et al., Neurology.
Abstract
Association of Leukocyte Telomere Length with Stroke, Dementia, and Late-Life Depression: The Role of Modifiable Risk Factors
Background and Objectives
Stroke, dementia, and late-life depression (LLD) are major, age-related conditions with substantial public health impact. Leukocyte telomere length (LTL) serves as a biological aging marker influenced by genetics and lifestyle. This study aimed to quantify associations between LTL and these brain diseases and to assess whether modifiable risk factors, summarized by the Brain Care Score (BCS), change those associations.
Methods
Researchers evaluated UK Biobank participants who had LTL measures and risk factor data. They examined associations between LTL and outcomes—stroke, dementia, and LLD—both separately and as a combined outcome, using continuous measures and tertile-based comparisons. Incidence was reported via cumulative incidence curves and rates per 1,000 person-years, with adjusted Cox proportional hazards models estimating risk. Participants were stratified by BCS (high BCS ≥ 15 indicating healthier profiles, low BCS ≤ 10 indicating less optimal profiles). Mendelian randomization was used to test for potential causal effects of LTL.
Results
The study included 356,173 participants (median age 56 years; 53.7% female). Shorter LTL was associated with higher incidence rates across the composite and individual outcomes. Compared with the longest LTL tertile, the shortest tertile had higher risk for the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08–1.15), stroke (HR 1.08; 95% CI 1.02–1.15), dementia (HR 1.19; 95% CI 1.12–1.26), and LLD (HR 1.14; 95% CI 1.09–1.18). Participants with both shorter LTL and low BCS experienced significantly higher risks across outcomes, while those with short LTL but high BCS did not show a significant risk increase. Mendelian randomization analyses did not support a clear causal relationship between LTL and these brain diseases.
Discussion
The findings indicate that shorter leukocyte telomere length is associated with greater risk of stroke, dementia, and late-life depression, but favorable modifiable risk profiles appear to reduce that association. These results highlight the potential value of lifestyle and clinical risk management for protecting brain health, even in people who show evidence of accelerated cellular aging. Future work should test whether targeted lifestyle interventions can slow or counteract aging-related processes that affect the brain.