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DoliClock: a lipid-based aging clock reveals accelerated aging in neurological disorders
Djakim Latumalea1,2,3, Maximilian Unfried1,3, Diogo Barardo1,3
1Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Aging
|June 7, 2025
Summary
This study introduces DoliClock, a lipid-based biological aging clock for the brain. It reveals accelerated aging in autism, schizophrenia, and Down syndrome, highlighting dolichol as a key aging biomarker.
Area of Science:
- Neuroscience
- Lipidomics
- Aging Research
Background:
- Lipid alterations are crucial in brain aging and neurological disorders.
- Understanding biological aging mechanisms is vital for disease intervention.
Purpose of the Study:
- To develop and validate DoliClock, a novel lipid-based biological aging clock for the prefrontal cortex.
- To investigate the role of lipidomics in brain aging and age-related neurological conditions.
Main Methods:
- Utilized post-mortem lipidomic data to construct the DoliClock.
- Analyzed age-related lipid changes and associated neurological disorders.
- Investigated dolichol accumulation and pathway dysregulation.
Main Results:
- DoliClock accurately predicts prefrontal cortex age from lipidomic data.
- Observed significant age acceleration in autism, schizophrenia, and Down syndrome.
- Identified increased entropy around age 40 linked to dolichol accumulation and mevalonate pathway dysregulation.
Conclusions:
- Lipidomics offers critical insights into brain aging and neurological disorders.
- Dolichol and entropy changes are potential biomarkers for accelerated biological aging.
- DoliClock demonstrates the potential of lipid-based biomarkers for predicting biological age, particularly in premature aging conditions.
