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Multidimensional Epigenetic Clocks Demonstrate Accelerated Aging Across Physiological Systems in Schizophrenia: A
Medrxiv : the Preprint Server for Health Sciences
|November 22, 2024
Summary
Multidimensional epigenetic clocks reveal accelerated aging in multiple organ systems in schizophrenia patients. This study highlights increased risks for heart, lung, metabolic, and brain aging, offering new insights into disease mechanisms.
Area of Science:
- Psychiatry
- Genetics
- Aging Research
Background:
- Schizophrenia is linked to accelerated aging, increased morbidity, and mortality.
- Previous studies used unidimensional epigenetic clocks, limiting granular insights into aging processes.
Purpose of the Study:
- To analyze biological aging in schizophrenia using novel multidimensional epigenetic clocks.
- To gain mechanistic insights into the relationship between schizophrenia, epigenetic aging, and health outcomes.
Main Methods:
- A meta-analysis of seven cross-sectional datasets including 1,891 schizophrenia patients and 1,881 controls.
- Analysis of multidimensional epigenetic clocks: CausAge, SystemsAge, RetroelementAge, DNAmEMRAge, and OMICmAge.
- Examined associations with schizophrenia status and clozapine use, controlling for age and sex.
Main Results:
- Multidimensional clocks (SystemsAge, CausAge, DNAmEMRAge, OMICmAge) showed accelerated epigenetic aging in schizophrenia.
- Ten SystemsAge sub-clocks indicated increased aging, particularly in Heart, Lung, Metabolic, and Brain systems.
- OMICmAge revealed changes in hematologic, hepatic markers, and novel proteins/metabolites; age acceleration observed at first psychotic episode.
Conclusions:
- This study presents the first analysis of multidimensional clocks in schizophrenia, offering a nuanced view of aging.
- Identifies multiple organ systems (Heart, Lung, Metabolic, Brain) at high risk in schizophrenia-related disorders.
- Provides novel insights into the mechanistic links between schizophrenia, epigenetic aging, and premature morbidity/mortality.
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