Biological aging acceleration in major depressive disorder: a multi-omics, multi-modal analyses

TL;DR

This study finds that depression is linked to faster biological aging, especially in the brain, and suggests targeting this aging could help treat depression and reduce health risks.

Contribution

The study identifies proteomic aging acceleration as a novel therapeutic target for MDD and reveals a causal link between MDD and biological aging.

Findings

MDD is associated with accelerated proteomic aging at systemic and brain levels.

Systemic and brain proteomic aging increases risks of MDD, dementia, and mortality.

Mendelian randomization shows a causal effect of MDD on biological aging acceleration.

Abstract

Major depressive disorder (MDD) is linked to a higher risk of premature aging, but the mechanisms underlying this association remain unclear. Using data from two population cohorts (UK Biobank and Finnish Twin Cohort), we evaluate the relationship between systemic and organ-specific proteomic and epigenetic aging acceleration and MDD. A lifetime history of MDD was associated with accelerated proteomic aging at both systemic and organ-specific levels—including the brain—in both cohorts, with stronger associations than those observed with systemic epigenetic aging. Systemic and brain proteomic aging acceleration were linked to higher risks of incident MDD and a greater risk of Alzheimer’s disease, related dementia, and mortality among individuals with MDD in the UK Biobank. Evidence of depressive episode remission attenuated the association between MDD and systemic and brain proteomic aging acceleration. Finally, Mendelian randomization analyses revealed a causal effect of MDD on systemic and brain proteomic aging acceleration. Our results suggest a strong bidirectional association between MDD and biological aging acceleration. Biological aging acceleration, assessed by proteomic systemic and organ-specific clocks, can serve as a novel therapeutic target for treating MDD and for mitigating the long-term risks of adverse health outcomes associated with this condition.

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