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

Journal: Aging
Published Date:

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.

Authors

  • Frank W Pun
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Geoffrey Ho Duen Leung
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Hoi Wing Leung
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Bonnie Hei Man Liu
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Xi Long
    1Department of Electrical EngineeringEindhoven University of Technology5612AZEindhovenThe Netherlands.
  • Ivan V Ozerov
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Ju Wang
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Feng Ren
    Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
  • Alexander Aliper
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.
  • Evgeny Izumchenko
    Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA.
  • Alexey Moskalev
    George Mason University, Fairfax, VA, United States.
  • João Pedro de Magalhães
    Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
  • Alex Zhavoronkov
    Pharmaceutical Artificial Intelligence Department, Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern, Baltimore, Maryland, USA.