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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.