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

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 S enescence- A ssociated S ecretory P henotype (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.

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

“…Several potential biological mechanisms have been proposed in linking immunological changes to affective neurobiology. MDD has been associated with immune cell senescence in particular, and a study by Diniz et al found that a senescence associated secretory phenotype was associated with MDD severity ( Diniz et al, 2019 ). Future research could examine the relationships between a broader range of inflammatory markers (e.g.…”

No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing

“…Although significant, the effect was relatively subtle, comparable to that identified in CpG methylation data. Diniz et al (2019) found MDD exhibited greater molecular senescence in young and middle-aged adults by examining the impact of MDD on the senescence associated secretory phenotype (SASP), a dynamic secretory molecular pathway indicative of cellular senescence 4 . More severe episodes of depression present with higher SASP indices and a significant interaction between current MDD episode and overweight, thus comorbid current MDD plus being overweight had the highest SASP index.…”

No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing

“…Immune cell senescence has a well-documented effect on both epigenome and transcriptome 3 . MDD has also been linked to the senescence associated secretory phenotype (SASP), a dynamic secretory molecular pathway indicative of cellular senescence 4 . This speaks to a more elaborate biology linking cell biology, transcriptome and inflammatory proteins produced by the cell.…”