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Telomere Shortening Linked to Depression and Cognitive Impairment in Older Adults

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Telomeres are repetitive sequences of DNA located at the ends of chromosomes that shorten with each division of somatic cells. This shortening is used as an indicator of cell replication history and potential. Telomere length (TL) plays a crucial role in human ageing, both at the cellular and systemic levels.

Older adults are at an increased risk of developing depression and neurocognitive impairment. Studies have shown that TL is associated with these conditions in elderly individuals. Late-life depression is linked to a higher risk of developing cognitive impairment, functional disability, and medical comorbidity burden compared to depression in young adults.

This increase in ageing-related somatic symptoms is thought to be a result of accelerated biological ageing in individuals with depression. Various hypotheses have been suggested to explain the emergence of a prematurely aged phenotype in late-life depression, including glucocorticoid cascade dysregulation, increased allostatic load, and telomere shortening.

TL has been reported to be associated with depression and cognitive impairment in older people. Early detection of depression and cognitive impairment is important to delay disease progression.

Researchers Myung-Hoon Han, Eun-Hye Lee, Hyun-Hee Park, Seong Hye Choi, and Seong-Ho Koh from Hanyang University and Inha University aimed to identify whether TL is associated with early subjective depressive symptoms and cognitive complaints among healthy older people. 

The findings were published in the journal Aging. 

“Several hypotheses have been proposed to explain the emergence of a prematurely aged phenotype in late-life depression, such as glucocorticoid cascade dysregulation, increased allostatic load, and telomere shortening,” explained the research authors.

This study was a multicenter, outcome assessor-blinded, 24-week, randomised controlled trial. Measurement of a questionnaire and physical activity scores and blood sample analyses were performed at baseline and after six months of follow-up in all study participants. Linear regression analyses were performed to identify whether early subjective depressive symptoms, cognitive complaints, and several blood biomarkers are associated with TL. 

Altogether, 137 relatively healthy elderly individuals (60–79 years old) were enrolled in this prospective RCT. The team observed an approximate decrease of 0.06 and 0.11−0.14 kbps of TL per one-point increase in the geriatric depression scale and cognitive complaint interview scores, respectively, at baseline and after six months of follow-up. They also found an approximate decrease of 0.08−0.09 kbps of TL per one-point increase in interleukin (IL)-6 levels at baseline and after six months of follow-up. 

“We showed that both early subjective depressive symptoms and cognitive complaints in relatively healthy elderly individuals were associated with a relatively shorter TL in the randomised controlled prospective SUPERBRAIN study. In addition, a shorter TL was associated with increased IL-6 levels in our study participants.

“We believe that IL-6, an inflammatory cytokine, plays an important role in the relationship of shortening TL with early subjective depressive mood and cognitive complaints. Although the results will need to be verified through a large-scale RCT in the future, we believe that our findings will help prevent and treat depression and cognitive impairment in the healthy elderly,” said the researchers.

Further research is needed to confirm these results, this study provides valuable insights into potential targets for interventions aimed at improving the health and well-being of the elderly population.

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