Shorter telomeres, which are the protective caps at the ends of chromosomes, may signal faster biological aging in cells and have been linked to a heightened risk of stroke, dementia, and late-life depression. This is based on an examination of over 356,000 individuals in the UK.
A preliminary study set to be showcased at the American Stroke Association’s International Stroke Conference 2025, scheduled for February 5-7 in Los Angeles, suggests that individuals with shorter telomeres might face a greater risk of developing age-related brain disorders, including stroke, dementia, and late-life depression, typically identified in individuals aged 60 and above.
The length of leukocyte telomeres, found in white blood cells, is a recognized marker for biological aging. As people age, these telomeres gradually get shorter, diminishing their capability to safeguard genetic material within chromosomes. This shortening process contributes to cellular aging and heightens the risk for age-related illnesses. Factors influencing telomere length include immutable elements like genetics, lineage, and gender, alongside adjustable factors such as lifestyle choices and environmental stressors like pollution.
According to Dr. Tamara N. Kimball, a postdoctoral research fellow at Massachusetts General Hospital, “No prior studies have explored the influence of leukocyte telomere length on a composite outcome comprising age-related brain diseases such as stroke, dementia, and late-life depression.” She notes that all these conditions are associated with cerebral small vessel disease, which is connected to both aging and the accumulation of vascular risk factors.
This study utilized data from over 356,000 participants from the extensive UK Biobank, addressing three key questions. When participants joined the study between 2006 and 2010, they provided blood samples to measure leukocyte telomere length and underwent a Brain Care Score assessment, which measures modifiable lifestyle factors, physical condition, and social interactions. They were tracked for a median of 12 years to observe the emergence of stroke, dementia, or late-life depression.
After looking into the correlation between shorter leukocyte telomeres and various conditions—both individually and collectively—researchers found:
- Participants with shorter leukocyte telomeres faced an 8% increased risk of stroke, a 19% increase in dementia risk, and a 14% rise in late-life depression risk compared to those with longer telomeres.
- In total, individuals with the shortest leukocyte telomere length had an 11% higher chance of developing at least one of the age-associated brain diseases studied, relative to those with longer telomeres.
Dr. Kimball mentioned, “In clinical settings, measuring leukocyte telomere length could help identify individuals who may require more vigilant monitoring or preventative strategies. It may aid in customizing interventions, such as lifestyle modifications and therapeutic measures, to improve overall health. However, since the current evidence linking leukocyte telomere length to stroke risk is preliminary, we do not recommend its routine use at this time.”
By employing a statistical method that aims to uncover potential causal relationships between exposure to certain risks and health outcomes, researchers were able to ascertain that leukocyte telomere length does not appear to cause stroke, dementia, or late-life depression.
Dr. Kimball further stated, “Our results imply that, while leukocyte telomere length is a commonly recognized indicator of biological aging, it does not directly instigate these age-related diseases. Instead, it may serve as a reflective marker representing underlying biological processes and cellular stress that precede these conditions.”
Upon examining how healthy habits could influence the relationship between leukocyte telomere length and age-associated brain ailments, the analysis revealed:
- For individuals with a low Brain Care Score, indicating a less favorable modifiable risk profile, shorter leukocyte telomeres notably increased (by 11%) the risk for stroke, dementia, and late-life depression when considered together.
- In contrast, among those with a high Brain Care Score, which signifies healthier lifestyle choices, there was no association between shorter leukocyte telomeres and an elevated risk of age-related brain disorders.
“This indicates that leading healthier lifestyles and enhancing modifiable risk factors could mitigate the adverse effects associated with shorter leukocyte telomeres. Essentially, it’s never too late to start caring for your brain,” stated Kimball.
Further investigation and long-term studies are necessary to unravel the dynamics of leukocyte telomere length over time, how it interacts with various risk factors, and its potential in personalized healthcare approaches.
“Rather than concentrating on creating therapeutic drugs to potentially modify telomere length—something that might carry risks—adopting a holistic strategy focused on lifestyle modifications might present a promising avenue for fostering healthier aging and diminishing the risks associated with these diseases,” Kimball concluded.
The study presents several limitations, notably its focus only on individuals of European descent, which may affect the applicability of its results to other demographics. The leukocyte telomere length and Brain Care Score were evaluated at the study’s outset, limiting the ability to observe changes over time. Although leukocyte telomere length serves as a marker for overall telomere length and is increasingly recognized as a sign of adverse cellular aging, it might not fully represent telomere length across different cell types beyond white blood cells.
Dr. Costantino Iadecola, director at Weill Cornell Medicine and not involved in this study, remarked, “This research indicates that the aging process directly influences the risk of significant age-related brain diseases, relatively independent of other risk factors. The established link between aging and conditions like stroke, dementia, and late-life depression, along with evidence clarifying that longer telomeres in white blood cells correlate with a lower risk of age-related brain diseases, points to a strong connection between the aging metabolism of the immune system and brain health.”
Study details, background, or design:
- The analysis encompassed over 356,000 participants from the UK Biobank, with an average age of 56 at study commencement (46% male).
- The leukocyte telomere length, an indicative marker of biological age, was assessed during participant enrollment. Individuals of non-European ancestry and blood relatives of other participants were excluded from the study.
- Participants joined the Biobank between 2006 and 2010, providing detailed baseline questionnaires, physical assessments, and biomedical evaluations, which facilitated the determination of leukocyte telomere length and the calculation of the Brain Care Score. This 19-point score encompasses modifiable factors related to brain health, such as blood pressure, dietary habits, exercise routines, and social-emotional elements like stress and social relationships. None had been diagnosed with stroke, dementia, or late-life depression at the study’s start.
- National health databases and periodic assessments monitored participants for a median of 12 years, tracking any diagnoses of stroke, dementia, or late-life depression.
- To examine the correlation between leukocyte telomere length and diagnoses, measurements were categorized into the shortest, middle, and longest thirds for analysis.
- Researchers applied a statistical method known as Mendelian Randomization to investigate potential causal links between leukocyte telomere length and these age-related brain diseases.
