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Biological Aging Acceleration in Major Depressive Disorder: A Multi-Omics Analysis
Breno Satler Diniz1,2, Shangshu Zhao2, Gabin Drouard3
1UConn Center on Aging, University of Connecticut Health Center, Farmington, Connecticut, USA.
Aging Cell
|December 4, 2025
Summary
Major depressive disorder (MDD) is linked to accelerated biological aging, particularly proteomic aging in the brain. This aging acceleration may be a causal factor and a potential therapeutic target for MDD.
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 aging acceleration are not fully understood.
Purpose of the Study:
- To investigate the relationship between proteomic and epigenetic aging acceleration and MDD.
- To explore whether aging acceleration is a causal factor in MDD and associated health risks.
Main Methods:
- Analysis of proteomic and epigenetic data from UK Biobank and Finnish Twin Cohort.
- Assessment of systemic and organ-specific aging acceleration.
- Mendelian randomization analyses to infer causality.
Main Results:
- Lifetime MDD history correlated with accelerated systemic and brain-specific proteomic aging.
- Proteomic aging acceleration was linked to higher risks of incident MDD, Alzheimer's disease, dementia, and mortality.
- Depressive episode remission attenuated these associations.
- Causal link found between MDD and proteomic aging acceleration.
Conclusions:
- MDD and biological aging acceleration exhibit a strong bidirectional relationship.
- Proteomic aging clocks may offer novel therapeutic targets for MDD treatment and risk mitigation.
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