Biomarker Associated With Premature Cell Aging May Indicate Stroke, Dementia and Late-Life Depression

People with shorter protective caps at the end of their chromosomes (known as telomeres) may be more likely to develop age-related brain disorders such as stroke, dementia and late-life depression (usually diagnosed after age 60), according to a preliminary study to be presented at the American Stroke Association’s International Stroke Conference 2025.

Leukocyte telomere length, which reflects the length of telomeres in white blood cells (leukocytes), is a well-known marker of biological aging. Telomeres gradually shorten with age, decreasing their ability to protect the genetic material of chromosomes, leading to cell aging and increased susceptibility to age-related diseases. Telomere length is influenced by unchangeable factors such as genetics, ancestry and gender, as well as changeable factors such as lifestyle and environmental exposures, including pollution.

Individuals With the Shortest Leukocyte Telomere Length Had a Higher Risk of Stroke, Dementia and Late-Life Depression

“There have been no studies examining the influence of leukocyte telomere length on a composite outcome of age-related brain diseases such as stroke, dementia, and late-life depression,” said Dr. Tamara N. Kimball, a postdoctoral fellow at the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital in Boston. “All three conditions are associated with small vessel cerebral disease, a condition linked to aging and the accumulation of vascular risk factors.”

The current study uses data from more than 356,000 participants in the large UK Biobank to answer three questions. When participants were recruited for the study between 2006 and 2010, they provided blood samples for leukocyte telomere length analysis. In addition, they underwent a brain-care-score evaluation, a tool used to quantify modifiable factors such as physical factors, lifestyle and social interactions. Participants were followed for an average of 12 years to monitor for the occurrence of stroke, dementia, or late-life depression.

After analyzing whether shorter leukocyte telomeres could be associated with stroke, dementia, and late-life depression, both individually and as a combined outcome, the analysis revealed the following:

• Compared with participants with longer leukocyte telomeres, individuals 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, people with the shortest leukocyte telomere length had an 11% higher risk of developing at least one of the age-related brain diseases studied compared to participants with longer leukocyte telomeres.

“In a clinical setting, leukocyte telomere length could help identify individuals who may require more intensive monitoring or preventive interventions. It could also guide personalized interventions, including lifestyle adjustments and therapeutic approaches, to improve overall health. However, because the evidence on the association between leukocyte telomere length and stroke risk is still exploratory, we do not currently recommend using leukocyte telomere length measurement as a standard procedure,” Kimball said.

Adopting Healthier Lifestyles and Improving the Profile of Modifiable Risk Factors can Reduce the Negative Effects of Shorter Leukocyte Telomeres

Using a statistical method that identifies potential causalities in the relationship between exposure and health outcomes, researchers can more accurately determine how certain risk factors can lead to health problems. This study found no evidence that leukocyte telomere length can cause stroke, dementia, or late-life depression. The results of the research suggest that although 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

After examining whether healthy behaviors could influence the association between leukocyte telomere length and age-related brain diseases, the analysis also showed that

• in people with a low Brain Care Score/less favorable modifiable risk factor profile, shorter leukocyte telomeres significantly increased the risk of stroke, dementia, and late-life depression as a combined outcome (by 11%).
• In contrast, in people with a high Brain Care Score, indicating a healthier lifestyle, shorter leukocyte telomeres were not associated with an increased risk of age-related brain disorders.

According to the experts, this indicates that a healthier lifestyle and improving one’s modifiable risk factor profile can reduce the negative effects of shorter leukocyte telomeres. In short, it is never too late to start taking better care of your brain. Further 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 can be used in personalized health strategies.

Rather than focusing on developing therapeutics to directly modify telomere length – which may carry potential risks – a holistic approach that focuses on modifiable lifestyle factors may offer a promising strategy for promoting healthier aging and reducing the risks of these diseases.

Relationship Between the Aging Clocks of the Immune System and the Brain

The study has several limitations. It focused exclusively on people of European descent, so the results may not be applicable to other populations. 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 an indicator of overall telomere length and is increasingly accepted as a marker of unfavorable cell aging, it may not reflect telomere length in cell types other than white blood cells.

This study suggests that the aging process directly influences the risk of severe age-related brain diseases, relatively independently 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 may be a sign of aging has significant clinical implications for risk assessment and prediction of health outcomes. There is evidence that longer telomeres in white blood cells are associated with a lower risk of severe age-related brain disorders. This suggests a strong link between the immune and brain aging clocks.