Shorter telomeres are linked to higher risks of stroke, dementia, and depression, but lifestyle factors may help counteract these effects.
- Shorter telomeres, the protective caps on chromosomes, are considered a marker of accelerated biological aging and may be linked to a higher risk of stroke, dementia, and late-life depression.
- Researchers analyzed data from over 356,000 people in the United Kingdom to explore this connection.
- The study found no evidence that shorter telomeres directly cause these brain diseases but suggests they may serve as an indicator of increased risk.
- Healthy lifestyle choices may help offset the negative effects of shorter telomeres, potentially reducing the risk of age-related brain diseases.
Shorter Telomeres and Brain Health Risks
People with shorter telomeres — the protective caps at the ends of their chromosomes — may have a higher risk of developing age-related brain diseases such as stroke, dementia, and late-life depression (typically diagnosed at age 60 or older). This finding comes from a preliminary study set to be presented at the American Stroke Association’s International Stroke Conference 2025, a leading global event for stroke and brain health research, taking place in Los Angeles from February 5-7, 2025.
Telomere length in white blood cells (leukocytes), known as leukocyte telomere length, is a well-established marker of biological aging. As people age, telomeres naturally shorten, reducing their ability to protect chromosomes, which accelerates cellular aging and increases vulnerability to age-related diseases. While telomere length is partly determined by genetics, ancestry, and gender, it is also influenced by lifestyle factors and environmental stressors such as diet, exercise, and pollution.
A New Look at Brain Disease Risk
“No studies have examined the impact of leukocyte telomere length on a composite outcome of age-related brain diseases that include stroke, dementia, and late-life depression,” said Tamara N. Kimball, M.D., a postdoctoral research fellow at the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital in Boston. “All three conditions are linked to cerebral small vessel disease, a condition associated with aging and accumulation of vascular risk factors.”
The current study uses data from more than 356,000 participants in the large UK Biobank to address three questions. When participants were recruited for the study between 2006 and 2010, they provided blood samples to analyze leukocyte telomere length. Additionally, they underwent a Brain Care Score assessment, a tool designed to quantify modifiable factors such as physical factors, lifestyle choices, and social interactions. Participants were followed for a median duration of 12 years to monitor the onset of stroke, dementia, or late-life depression.
Telomere Length and Disease Risk
After analyzing whether shorter leukocyte telomeres were associated with stroke, dementia, and late-life depression individually and as a combined outcome, the analysis found:
- Compared to participants with longer leukocyte telomeres, people with the shortest leukocyte telomere length had an 8% higher risk of stroke, a 19% higher risk of dementia, and a 14% higher risk of late-life depression.
- Overall, compared to participants with longer leukocyte telomeres, people with the shortest leukocyte telomere length had an 11% higher risk of developing at least one of the age-related brain diseases studied.
“In a clinical setting, leukocyte telomere length could help identify people who may need more intensive monitoring or preventive measures. It could also guide personalized interventions, including lifestyle adjustments and therapeutic approaches, to enhance overall health. However, given that the evidence linking leukocyte telomere length to stroke risk is still exploratory, we currently do not suggest leukocyte telomere length measurement be used as a standard practice,” Kimball said.
Using a statistical method that identifies potential causality in the relationship between exposure and health outcomes, researchers can more accurately determine how certain risk factors may lead to health conditions. This study found no evidence that leukocyte telomere length may cause stroke, dementia or late-life depression.
“Our findings suggest that, while leukocyte telomere length may be a well-known indicator of biological aging, it does not directly cause these age-related diseases. Instead, leukocyte telomere length may act more as a reflective marker of underlying biological processes and cellular stress that precede these age-related diseases,” Kimball said.
Lifestyle’s Role in Brain Health
After exploring whether healthy behaviors can influence the association between leukocyte telomere length and age-related brain diseases, the analysis also found:
- In people with a low Brain Care Score/less favorable modifiable risk factor profile, shorter leukocyte telomeres significantly increased (by 11%) the risk for stroke, dementia and late-life depression as a combined outcome.
- Conversely, among people with a high Brain Care Score, indicating healthier lifestyle choices, shorter leukocyte telomeres were not associated with an increased risk of age-related brain diseases.
“This suggests that adopting healthier lifestyles and improving modifiable risk factor profile may lower the negative effects of shorter leukocyte telomeres. In short, it is never too late to start taking better care of your brain,” said Kimball.
More research and longer studies are needed to understand the dynamics of leukocyte telomere length over time, how it interacts with various risk factors, and how it might be used in personalized healthcare strategies.
A Holistic Approach to Aging
“Rather than focusing on developing therapeutic drugs to directly alter telomere length – which may carry potential risks – a holistic approach centered on modifiable lifestyle factors might offer a promising strategy for promoting healthier aging and reducing the risks of these diseases,” Kimball said.
The study has several limitations. It focused solely on people of European ancestry, so the results may not be generalizable to other populations. The leukocyte telomere length and the Brain Care Score were measured at baseline, so the researchers could not analyze changes over time. While leukocyte telomere length is a proxy for overall telomere length and is increasingly accepted as a marker of adverse cellular aging, it may not represent telomere length in cell types other than white blood cells.
The Aging Clock and Brain Disease
“This study suggests that the aging process directly impacts the risk of major age-related brain diseases, relatively independent of other risk factors. While the link between aging and stroke, dementia and late-life depression is well established, the finding that telomere shortening in white blood cells can be a sign of aging holds significant clinical implications for assessing risks and predicting health outcomes,” said Costantino Iadecola, M.D., FAHA, director and chair of the Feil Family Brain and Mind Research Institute and Anne Parrish Titzell Professor of Neurology at Weill Cornell Medicine, New York. ”Recent research shows that different parts of the body age at different rates, each with its own “aging clock.” Evidence suggests that longer telomeres in white blood cells are connected to a lower risk of major brain diseases related to aging. This indicates a strong link between the aging clock of the immune system and the brain.” Iadecola was not involved in this study.
Study details, background, and design:
- The analysis included more than 356,000 participants (average age 56 at the start of the study, 46% men) in the UK Biobank (a large-scale population-based prospective study that has enrolled over half a million volunteer participants from 22 centers in the United Kingdom).
- Leukocyte telomere length (a proposed marker of biological age) was measured at enrollment. Because leukocyte telomere length is associated with genetics and ancestry, people were excluded if their ancestry was other than European and if they were blood relatives of anyone else in the study.
- Participants were enrolled in the Biobank between 2006 and 2010, during which detailed baseline questionnaires, physical measurements, and biomedical assessments were obtained. These were used to assess the leukocyte telomere length and calculate the Brain Care Score. This 19-point scale includes potentially modifiable factors (such as blood pressure), lifestyle factors (such as diet and exercise), and social/emotional factors (such as stress and the strength of social relationships) related to brain health. None of the participants had been diagnosed with stroke, dementia, or late-life depression at the beginning of the study.
- Using national health databases and periodic medical assessments, participants were tracked for a median of 12 years for the diagnosis of stroke, dementia, or late-life depression.
- To assess the association of leukocyte telomere length with the diagnoses, leukocyte telomere length measurements were divided into the shortest, intermediate, and longest thirds for analysis.
- Researchers used a statistical method called Mendelian Randomization to explore whether there is a causal association between leukocyte telomere length and these age-related brain diseases.
Meeting: ASA International Stroke Conference 2025
Note: The study featured in this news release is a research abstract. Abstracts presented at the American Heart Association’s scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.
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