Major depression and enhanced molecular senescence abnormalities in young and middle-aged adults

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Abstract

Recent evidence suggests a significant overlap in biological changes between major depression and aging across the lifespan. We aim to evaluate the impact of a major depressive episode on the Senescence- Associated Secretory Phenotype (SASP) index, a dynamic secretory molecular pattern indicative of cellular senescence. We also tested the potential moderators of the association between major depression and the SASP index. We included 1165 young and middle-aged adults (527 with a current major depressive episode (cMDE) and 638 with no lifetime history of depression) from a community-based cohort from the Netherlands. We calculated the SASP index based on a previously developed composite index involving 19 biomarkers. cMDE had higher SASP index values (t ₍₁₁₆₃₎ = 2.93, p = 0.003) compared to controls in the univariate analysis. After controlling for sociodemographic and somatic health covariates, there was no significant association between cMDE and SASP index (F _(1,1158) = 1.09, p = 0.29). Those with the most severe depressive episodes had significantly higher SASP indices compared to those with mild-to-moderate cMDE and controls (F _(2,1162) = 6.73, p = 0.001). We found a significant interaction between cMDE and overweight (F _(1,1164) = 5.1, p = 0.028): those with comorbid cMDE and overweight had the highest SASP index. Our study demonstrated a complex interaction between cMDE and medical morbidity, especially overweight, on the SASP index, suggesting that their coexistence aggravate age-related biological processes. Moreover, higher SASP index can be a biomarker for more severe depressive episodes.

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Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative.

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Author and article information

Contributors

Breno S. Diniz:

ORCID: http://orcid.org/0000-0003-0653-1905

breno.diniz@camh.ca

Journal

Journal ID (nlm-ta): Transl Psychiatry

Journal ID (iso-abbrev): Transl Psychiatry

Title: Translational Psychiatry

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2158-3188

Publication date (Electronic): 21 August 2019

Publication date PMC-release: 21 August 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 198

Affiliations

[1 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Adult Neurodevelopment and Geriatric Psychiatry Division, , Centre for Addiction and Mental Health, ; Toronto, ON Canada

[2 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Psychiatry, Faculty of Medicine, , University of Toronto, ; Toronto, ON Canada

[3 ]ISNI 0000 0000 8793 5925, GRID grid.155956.b, Campbell Family Mental Health Research Institute, , Centre for Addiction and Mental Health, ; Toronto, ON Canada

[4 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Psychiatry, , University of Pittsburgh School of Medicine, ; Pittsburgh, PA USA

[5 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, Department of Pharmacology and Toxicology, , University of Toronto, ; Toronto, ON Canada

[6 ]ISNI 0000 0004 1754 9227, GRID grid.12380.38, Amsterdam Public Health Research Institute, Department of Psychiatry, , Amsterdam UMC, Vrije Universiteit, ; Amsterdam, The Netherlands

Author information

Breno S. Diniz http://orcid.org/0000-0003-0653-1905

Article

Publisher ID: 541

DOI: 10.1038/s41398-019-0541-3

PMC ID: 6704136

PubMed ID: 31434875

SO-VID: 74b0a969-49a6-4821-82dd-054ca3f9bc7c

License:

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