Biological aging acceleration in major depressive disorder: a multi-omics, multi-modal analyses
Breno Diniz1, Shangshu Zhao1, Gabin Drouard2
1UConn School of Medicine.
Research Square
|June 12, 2025
Summary
Major depressive disorder (MDD) is linked to accelerated biological aging, particularly proteomic aging in the brain. This accelerated aging may be a causal factor and a potential therapeutic target for MDD and its associated health risks.
Area of Science:
- Biomedical Science
- Genetics
- Neuroscience
Background:
- Major depressive disorder (MDD) is associated with increased risk of premature aging.
- The underlying biological mechanisms linking MDD and accelerated aging are not fully understood.
Purpose of the Study:
- To investigate the relationship between MDD and biological aging acceleration using proteomic and epigenetic markers.
- To explore whether accelerated aging causally influences MDD risk and adverse health outcomes.
Main Methods:
- Analysis of systemic and organ-specific proteomic and epigenetic aging acceleration in two large cohorts (UK Biobank, Finnish Twin Cohort).
- Assessment of associations with MDD history, incident MDD, and related health outcomes (Alzheimer's disease, dementia, mortality).
- Mendelian randomization analyses to infer causality.
Main Results:
- Lifetime history of MDD was significantly associated with accelerated proteomic aging (systemic and brain-specific) in both cohorts.
- Proteomic aging acceleration was linked to higher risks of incident MDD, Alzheimer's disease, dementia, and mortality.
- Depressive episode remission attenuated the observed aging acceleration.
- Mendelian randomization supported a causal effect of MDD on proteomic aging acceleration.
Conclusions:
- MDD exhibits a strong bidirectional association with biological aging acceleration, particularly proteomic aging.
- Proteomic aging acceleration is a potential therapeutic target for MDD and for mitigating associated long-term health risks.
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