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Research Paper|Volume 14, Issue 6|pp 2475—2506

Hallmarks of aging-based dual-purpose disease and age-associated targets predicted using PandaOmics AI-powered discovery engine

Frank W. Pun1, Geoffrey Ho Duen Leung1, Hoi Wing Leung1, Bonnie Hei Man Liu1, Xi Long1, Ivan V. Ozerov1, Ju Wang1, Feng Ren1, Alexander Aliper1, Evgeny Izumchenko2, Alexey Moskalev3, João Pedro de Magalhães4, Alex Zhavoronkov1,5
  • 1Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China
  • 2Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA
  • 3School of Systems Biology, George Mason University (GMU), Fairfax, VA 22030, USA
  • 4Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
  • 5Buck Institute for Research on Aging, Novato, CA 94945, USA
* Equal contribution
Received: January 21, 2022Accepted: March 6, 2022Published: March 29, 2022

Copyright: © 2022 Pun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging biology is a promising and burgeoning research area that can yield dual-purpose pathways and protein targets that may impact multiple diseases, while retarding or possibly even reversing age-associated processes. One widely used approach to classify a multiplicity of mechanisms driving the aging process is the hallmarks of aging. In addition to the classic nine hallmarks of aging, processes such as extracellular matrix stiffness, chronic inflammation and activation of retrotransposons are also often considered, given their strong association with aging. In this study, we used a variety of target identification and prioritization techniques offered by the AI-powered PandaOmics platform, to propose a list of promising novel aging-associated targets that may be used for drug discovery. We also propose a list of more classical targets that may be used for drug repurposing within each hallmark of aging. Most of the top targets generated by this comprehensive analysis play a role in inflammation and extracellular matrix stiffness, highlighting the relevance of these processes as therapeutic targets in aging and age-related diseases. Overall, our study reveals both high confidence and novel targets associated with multiple hallmarks of aging and demonstrates application of the PandaOmics platform to target discovery across multiple disease areas.