Back to Search Start Over

A comprehensive AI‐driven analysis of large‐scale omic datasets reveals novel dual‐purpose targets for the treatment of cancer and aging.

Authors :
Pun, Frank W.
Leung, Geoffrey Ho Duen
Leung, Hoi Wing
Rice, Jared
Schmauck‐Medina, Tomas
Lautrup, Sofie
Long, Xi
Liu, Bonnie Hei Man
Wong, Chun Wai
Ozerov, Ivan V.
Aliper, Alex
Ren, Feng
Rosenberg, Ari J.
Agrawal, Nishant
Izumchenko, Evgeny
Fang, Evandro F.
Zhavoronkov, Alex
Source :
Aging Cell; Dec2023, Vol. 22 Issue 12, p1-19, 19p
Publication Year :
2023

Abstract

As aging and tumorigenesis are tightly interconnected biological processes, targeting their common underlying driving pathways may induce dual‐purpose anti‐aging and anti‐cancer effects. Our transcriptomic analyses of 16,740 healthy samples demonstrated tissue‐specific age‐associated gene expression, with most tumor suppressor genes downregulated during aging. Furthermore, a large‐scale pan‐cancer analysis of 11 solid tumor types (11,303 cases and 4431 control samples) revealed that many cellular processes, such as protein localization, DNA replication, DNA repair, cell cycle, and RNA metabolism, were upregulated in cancer but downregulated in healthy aging tissues, whereas pathways regulating cellular senescence were upregulated in both aging and cancer. Common cancer targets were identified by the AI‐driven target discovery platform—PandaOmics. Age‐associated cancer targets were selected and further classified into four groups based on their reported roles in lifespan. Among the 51 identified age‐associated cancer targets with anti‐aging experimental evidence, 22 were proposed as dual‐purpose targets for anti‐aging and anti‐cancer treatment with the same therapeutic direction. Among age‐associated cancer targets without known lifespan‐regulating activity, 23 genes were selected based on predicted dual‐purpose properties. Knockdown of histone demethylase KDM1A, one of these unexplored candidates, significantly extended lifespan in Caenorhabditis elegans. Given KDM1A's anti‐cancer activities reported in both preclinical and clinical studies, our findings propose KDM1A as a promising dual‐purpose target. This is the first study utilizing an innovative AI‐driven approach to identify dual‐purpose target candidates for anti‐aging and anti‐cancer treatment, supporting the value of AI‐assisted target identification for drug discovery. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14749718
Volume :
22
Issue :
12
Database :
Complementary Index
Journal :
Aging Cell
Publication Type :
Academic Journal
Accession number :
174293123
Full Text :
https://doi.org/10.1111/acel.14017