Longer Telomeres Tied to Better Brain Health

Telomere shortening — a sign of cellular aging — is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” Anya Topiwala, University of Oxford, told Medscape Medical News.

“We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Topiwala said.

The study was published online March 22 in PLOS ONE.

UK Biobank Cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease (AD).

The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank.

They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus — both of which shrink in patients with AD. Longer telomeres were also associated with a thicker cerebral cortex, which thins as AD progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% CI, 0.91-0.96).

Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Topiwala told Medscape Medical News.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population.

Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.

Need for More Research

Commenting on this research for Medscape Medical News, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres — the caps at the end of DNA — are associated with increased aging.”

This new study is “interesting,” said Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with AD. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Topiwala, “association does not mean causation,” Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Griffin said.

The study had no specific funding. Topiwala and Griffin report no relevant disclosures.

PLOS ONE. Published online March 22, 2023. Full text

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