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Stress and telomere length in leukocytes : investigating the role of GABRA6 gene polymorphism and cortisol

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Abstract
Telomere length (TL) is considered a biomarker of aging, and short TL in leukocytes is related to age and stress- related health problems. Cumulative lifetime stress exposure has also been associated with shorter TL and age- related health problems, but the mechanisms are not well understood. We tested in 108 individuals whether shorter TL in leukocytes is observed in individuals with the GABRA6 TT genotype, which has been associated with dysregulation of hypothalamic-pituitary-adrenal axis activity (the main biological stress system) compared to the CC genotype. We also investigated if individuals carrying the TT genotype show higher stress-induced and diurnal cortisol secretion and if cortisol explains the interindividual variability in TL. The analysis pipeline of this study was pre-registered, and the results showed that GABRA6 TT carriers had shorter TL in CD8+CD28+ cells (Bonferroni corrected). In contrast to previous studies, no differences between groups in cortisol secretion were observed, and TL and cortisol did not show significant associations. This study shows, for the first time, shorter TL in CD8+CD28+ cells in TT carriers for GABRA6 compared to CC carriers, suggesting accelerated cellular aging. Although this difference could be linked to an increased susceptibility to stress in the TT carriers, this could not be attributed to the direct influence of cortisol, suggesting the involvement of other mechanisms.
Keywords
Stress, GABA, GABRA6, Cortisol, Telomere length, CARDIOVASCULAR-DISEASE, MONOAMINE-OXIDASE, CIGARETTE-SMOKING, EXPRESSION, ALLOSTASIS, RESPONSES, PATTERNS, PROMOTER, OBESITY, GENDER

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Citation

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MLA
Martino, Pablo, et al. “Stress and Telomere Length in Leukocytes : Investigating the Role of GABRA6 Gene Polymorphism and Cortisol.” PSYCHONEUROENDOCRINOLOGY, vol. 173, 2025, doi:10.1016/j.psyneuen.2025.107358.
APA
Martino, P., Perez-Alarcón, M., Deconinck, L., De Raedt, R., Vanderhasselt, M.-A., Kozusznik, G., … Pulópulos Tripiana, M. M. (2025). Stress and telomere length in leukocytes : investigating the role of GABRA6 gene polymorphism and cortisol. PSYCHONEUROENDOCRINOLOGY, 173. https://doi.org/10.1016/j.psyneuen.2025.107358
Chicago author-date
Martino, Pablo, Mario Perez-Alarcón, Luna Deconinck, Rudi De Raedt, Marie-Anne Vanderhasselt, Gosia Kozusznik, Frank Kooy, et al. 2025. “Stress and Telomere Length in Leukocytes : Investigating the Role of GABRA6 Gene Polymorphism and Cortisol.” PSYCHONEUROENDOCRINOLOGY 173. https://doi.org/10.1016/j.psyneuen.2025.107358.
Chicago author-date (all authors)
Martino, Pablo, Mario Perez-Alarcón, Luna Deconinck, Rudi De Raedt, Marie-Anne Vanderhasselt, Gosia Kozusznik, Frank Kooy, Vanesa Hidalgo, César Venero, Alicia Salvador, Chris Baeken, and Matias Miguel Pulópulos Tripiana. 2025. “Stress and Telomere Length in Leukocytes : Investigating the Role of GABRA6 Gene Polymorphism and Cortisol.” PSYCHONEUROENDOCRINOLOGY 173. doi:10.1016/j.psyneuen.2025.107358.
Vancouver
1.
Martino P, Perez-Alarcón M, Deconinck L, De Raedt R, Vanderhasselt M-A, Kozusznik G, et al. Stress and telomere length in leukocytes : investigating the role of GABRA6 gene polymorphism and cortisol. PSYCHONEUROENDOCRINOLOGY. 2025;173.
IEEE
[1]
P. Martino et al., “Stress and telomere length in leukocytes : investigating the role of GABRA6 gene polymorphism and cortisol,” PSYCHONEUROENDOCRINOLOGY, vol. 173, 2025.
@article{01JJ4C1MRD6T1VHAC9MYMNG8CD,
  abstract     = {{Telomere length (TL) is considered a biomarker of aging, and short TL in leukocytes is related to age and stress- related health problems. Cumulative lifetime stress exposure has also been associated with shorter TL and age- related health problems, but the mechanisms are not well understood. We tested in 108 individuals whether shorter TL in leukocytes is observed in individuals with the GABRA6 TT genotype, which has been associated with dysregulation of hypothalamic-pituitary-adrenal axis activity (the main biological stress system) compared to the CC genotype. We also investigated if individuals carrying the TT genotype show higher stress-induced and diurnal cortisol secretion and if cortisol explains the interindividual variability in TL. The analysis pipeline of this study was pre-registered, and the results showed that GABRA6 TT carriers had shorter TL in CD8+CD28+ cells (Bonferroni corrected). In contrast to previous studies, no differences between groups in cortisol secretion were observed, and TL and cortisol did not show significant associations. This study shows, for the first time, shorter TL in CD8+CD28+ cells in TT carriers for GABRA6 compared to CC carriers, suggesting accelerated cellular aging. Although this difference could be linked to an increased susceptibility to stress in the TT carriers, this could not be attributed to the direct influence of cortisol, suggesting the involvement of other mechanisms.}},
  articleno    = {{107358}},
  author       = {{Martino, Pablo and Perez-Alarcón, Mario and Deconinck, Luna and De Raedt, Rudi and Vanderhasselt, Marie-Anne and Kozusznik, Gosia and Kooy, Frank and Hidalgo, Vanesa and Venero, César and Salvador, Alicia and Baeken, Chris and Pulópulos Tripiana, Matias Miguel}},
  issn         = {{0306-4530}},
  journal      = {{PSYCHONEUROENDOCRINOLOGY}},
  keywords     = {{Stress,GABA,GABRA6,Cortisol,Telomere length,CARDIOVASCULAR-DISEASE,MONOAMINE-OXIDASE,CIGARETTE-SMOKING,EXPRESSION,ALLOSTASIS,RESPONSES,PATTERNS,PROMOTER,OBESITY,GENDER}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{Stress and telomere length in leukocytes : investigating the role of GABRA6 gene polymorphism and cortisol}},
  url          = {{http://doi.org/10.1016/j.psyneuen.2025.107358}},
  volume       = {{173}},
  year         = {{2025}},
}

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