Shorter Telomere Length Linked to Increased Risk of Stroke, Dementia, Depression

Shorter protective caps on chromosomes called telomeres, a proposed marker of accelerated biological aging, may be linked to an increased risk of stroke, dementia, and late-life depression.1

Telomere length was not shown to cause age-related brain diseases directly, but the recent analysis suggested healthier lifestyle choices may significantly counteract the harmful effects of shorter telomeres. The preliminary findings will be presented at the American Stroke Association International Stroke Conference 2025 in Los Angeles from February 5 – 7, 2025.

“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,” said investigator Tamara N. Kimball, MD, a postdoctoral research fellow at the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital in Boston, in a statement.2 “Instead, leukocyte telomere length may act more as a reflective marker of underlying biological processes and cellular stress that precede these age-related diseases.”

Recent studies have demonstrated that different parts of the body age at different rates. Evidence indicates longer telomeres in white blood cells are associated with a lower risk of major age-related brain diseases.

A complex interplay of modifiable lifestyle and nonmodifiable heritable factors influence leukocyte telomere length.1 For instance, while genetics, ancestry, and gender may be unchangeable factors, environmental stressors such as pollution could be modified.

Telomeres shorten with age, reducing their ability to protect chromosome’s genetic material. This results in cellular aging and increased susceptibility to age-related diseases.

The telomere length may bring insight into the modifiability of age-related brain diseases. In their study, investigators sought to assess the link between leukocyte telomere length and the diseases of stroke, dementia, and late-life depression.

Leveraging data from the UK Biobank, the team included 356,173 participants with valid leukocyte telomere length measurements who were followed for a median duration of 12 years to monitor the onset of stroke, dementia, or late-life depression. The mean age was 56.97 years, and 46.31% were male.

Investigators accounted for modifiable lifestyle risk factors when assessing the Brain Care Score, a 21-point metric validated for age-related brain diseases. A modified 19-point Brain Scare Score was also assessed, taking into consideration modifiable factors, such as blood pressure, diet, exercise, stress, and strength of social relationships. The team divided valid leukocyte telomere length measurements into tertiles. Participants were also stratified into 3 age groups: < 50 years, 50 – 59 years, and ≥ 60 years).

The analysis demonstrated that with longer leukocyte telomere length, there were lower incidence rates for stroke, dementia, and late-life depression. Compared with participants who had longer leukocyte telomeres, people with the shortest leukocyte telomere length had an 8% greater risk of stroke (longest length, HR, 0.87; 95% CI, 0.83 – 0.92), a 19% risk of dementia (longest length, HR, 0.77; 95% CI, 0.72 – 0.82), and a 14% greater risk of late-life depression (longest, HR, 0.88; 95% CI, 0.84 – 0.91)—not to mention a 11% greater risk of developing ≥ 1 age-related brain diseases.

People with a low Brain Care score who had shorter leukocyte telomeres had an 11% increased risk for stroke, dementia, and late-life depression. Moreover, in people with a high Brain Care Score, suggesting a healthier lifestyle, shorter leukocyte telomeres were not linked to an increased risk of age-related brain diseases.

Investigators note this finding indicates adopting a healthy lifestyle and improving modifiable risk factors could reduce the negative effects of shorter leukocyte telomeres.

“In short, it is never too late to start taking better care of your brain,” Kimball said.2

Investigators wrote the findings were limited by solely focusing on a European population and only measuring leukocyte telomere length and Brain Scare Score at baseline, making it so investigators could not assess changes over time. Ultimately, longer studies are needed to understand how leukocyte telomere length over time interacts with risk factors.

“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.

References

1. Leukocyte Telomere Length as a Predictor of Age-Related Brain Diseases: Evidence from the UK Biobank. Poster presented at American Stroke Association International Stroke Conference 2025 in Los Angeles from February 5 – 7, 2025 in Los Angeles.
2. Biomarker tied to premature cell aging may signal stroke, dementia, late-life depression. EurekAlert! January 30, 2025. https://www.eurekalert.org/news-releases/1071544. Accessed February 3, 2025.