Mol Psychiatry. 2025 Oct 7. doi: 10.1038/s41380-025-03296-3. Online ahead of print.
ABSTRACT
Recent research has increasingly focused on understanding the relationship between cellular aging and mental health, particularly Major Depressive Disorder (MDD). Telomeres, protective structures at the end of chromosomes, and telomerase, an enzyme responsible for their maintenance, have emerged as potential markers of cellular aging and targets for therapeutic interventions in MDD. This review synthesizes findings from 30 studies conducted over the past 15 years, examining alterations in telomere length (TL) and telomerase activity (TA) in individuals with MDD compared to healthy controls. Most studies reported shorter TL in MDD patients, particularly in cases of chronic or severe depression, determined by the duration of illness or illness episode and by measurements of depression severity (e.g. HAM-D, BDI, etc.), suggesting an association between MDD and accelerated cellular aging. Elevated TA was also observed in MDD, with potential implications for treatment response. However, conflicting findings and methodological variations highlight the complexity of the relationship between TL, TA, and MDD, warranting further research. Additionally, studies investigating other biomarkers of cellular aging, such as mitochondrial DNA, provide further insights into the pathophysiology of MDD. Studies on brain cells reveal regional variations in telomere dynamics, suggesting a nuanced relationship between depression and cellular aging across different brain regions. While evidence suggests a potential reversibility of TL alterations in MDD, further research is needed to elucidate underlying mechanisms and develop targeted interventions. Overall, this review underscores the importance of understanding cellular aging processes in MDD and their potential implications for diagnosis, treatment, and the development of novel therapeutic strategies.
PMID:41053437 | DOI:10.1038/s41380-025-03296-3
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