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Research Paper|Volume 17, Issue 6|pp 1405—1428

DoliClock: a lipid-based aging clock reveals accelerated aging in neurological disorders

Djakim Latumalea1,2,3, Maximilian Unfried1,3, Diogo Barardo1,3, Jan Gruber1,3,6, Brian K. Kennedy1,3,4,5
  • 1Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 2Institute for Life Sciences and Technology, Hanze University of Applied Sciences, Groningen, The Netherlands
  • 3Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 4Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  • 5Centre for Healthy Longevity, National University of Singapore, Singapore
  • 6Science Division, Yale-NUS College, Singapore
Received: January 3, 2025Accepted: May 14, 2025Published: June 4, 2025
https://doi.org/10.18632/aging.206266

Copyright: © 2025 Latumalea et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging is a multifaceted process influenced by intrinsic and extrinsic factors, with lipid alterations playing a critical role in brain aging and neurological disorders. This study introduces DoliClock, a lipid-based biological aging clock designed to predict the age of the prefrontal cortex using post-mortem lipidomic data. Significant age acceleration was observed in autism, schizophrenia, and Down syndrome. Additionally, an increase in entropy around age 40 suggests dysregulation of the mevalonate pathway and dolichol accumulation. Dolichol, a lipid integral to N-glycosylation and intracellular transport, emerged as a potential aging biomarker, with specific variants such as dolichol-19 and dolichol-20 showing unique age-related associations. These findings suggest that lipidomics can provide valuable insights into the molecular mechanisms of brain aging and neurological disorders. By linking dolichol levels and entropy changes to accelerated aging, this study highlights the potential of lipid-based biomarkers for understanding and predicting biological age, especially in conditions associated with premature aging.