Summary: New research shows that healthy lifestyle choices can reduce the risk of stroke, dementia, and depression, even in people with biologically shortened telomeres. Telomeres are protective DNA caps that naturally shrink with age and environmental stress, increasing vulnerability to age-related brain diseases.
In a study of over 356,000 individuals, those with shorter telomeres but healthier behaviors had no elevated risk compared to peers with longer telomeres. These findings highlight the power of lifestyle interventions in promoting brain health, even amid signs of accelerated cellular aging.
Key Facts:
- Telomere Risk: Short telomeres are linked to increased risk of stroke, dementia, and late-life depression.
- Lifestyle Buffer: A high brain health score—reflecting good sleep, diet, activity, and low alcohol use—may neutralize the effects of telomere shortening.
- Actionable Insight: Even people with biological aging markers can benefit from lifestyle improvements.
Source: Mass General
Scientists from Mass General Brigham explored the associations between telomere length—which decreases as a person ages or is exposed to unhealthy environments—and the risk for age-related brain diseases.
The research team found evidence suggesting that healthier lifestyle choices could mitigate telomere length-associated risks.
Their results are 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, a founding member of the Mass General Brigham healthcare system. “In short, it is never too late to start taking better care of your brain.”
The risk of stroke, dementia, and late-life depression (LLD) increases for people as they get older. Likewise, telomeres, which are protective caps on chromosomes, naturally shorten with age, or exposure to adverse environmental conditions, like stress and pollution, increasing the risk for DNA damage.
This study sought to determine the association between these age-related brain diseases and leukocyte telomere length (LTL), and whether LTL was a direct causal factor or merely a predictive marker for brain diseases.
To investigate this relationship, the research team analyzed data from 356,173 participants in the UK Biobank. They also used the McCance Brain Care Score (BCS), which accounts for factors like blood pressure, blood sugar levels, cholesterol, and lifestyle behaviors, and social-emotional aspects that influence risk factor profiles.
Their findings showed that individuals with shorter LTLs and lower BCSs, reflecting less optimal lifestyle choices, were at greater risk for these brain diseases. Notably, those with shorter LTLs but healthier lifestyle scores (high BCS) did not show a significantly increased risk, suggesting that a high BCS may mitigate the effects of short telomeres.
One notable limitation of the study was that LTL was only measured at the initial visit, and so telomere shortening could not be tracked over time. Additionally, the study only included individuals of European descent, which limits its generalizability.
Nevertheless, reducing risk factors appears to mitigate the negative effects of shorter telomeres on cerebral health, which sets the stage for future studies to explore whether lifestyle interventions can in fact slow aging’s effects on the brain.
Authorship: In addition to Kimball, Mass General Brigham authors include Savvina Prapiadou, Reinier WP Tack, Benjamin YQ Tan, Jasper R. Senff, Chrisna Kourkoulis, Sanjula D. Singh, Jonathan Rosand, Christopher D. Anderson.
Disclosures: None.
Funding: This study was funded in part by the National Institutes of Health (T32 Fellowship NS100663-06A1, R01NS103924, and U01NS069673), the American Heart Association (18SFRN34250007), the American Heart Association (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 age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors.
The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.
Methods
We analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL’s associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification.
Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.
Results
The study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of 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).
Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07–1.16) and individually for stroke (HR 1.10; 95% CI 1.02–1.19), dementia (HR 1.17; 95% CI 1.08–1.28), and LLD (HR 1.13; 95% CI 1.07–1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal relationships between LTL and these outcomes.
Discussion
Individuals with shorter LTL are at increased risk of stroke, dementia, and LLD. Improved modifiable risk factor profiles seem to mitigate the impact of LTL on these diseases. Future research should explore the effectiveness of lifestyle interventions in mitigating adverse biological aging effects on brain health.
