Brian Kennedy, PhD, NUS | National University of Singapore; Vincenzo Sorrentino, PhD, NUS; Jan Gruber, PhD, NUS; Kamil Pabis, MSc, NUS; Oliver Dreesen, PhD, ASTAR; Tay Jian Hua, MSc, NUS
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee Year: 2025
Our long-term goal is to find drugs that can slow the process of aging, thereby improve neurocognitive outcomes in the elderly, and substantially boosting healthy lifespans. Towards this goal, we aim to develop a new in vitro epigenetic clock (“CellPopAgeV2”) and use it screen for drugs that reverse epigenetic aging clocks. The CellPopAgeV2 clock will be a dual-purpose clock optimized for high-throughput screening which captures aspects of in vitro cell aging, while maintaining the ability of predicting mortality from blood.
Furthermore, we will combine the screening hits with data from internal screens and published databases to identify candidates most likely to improve aging, progeroid and neurodegenerative phenotypes. The internal screens include a large screen for lifespan extending drugs in yeast and another screen for activators of the TFEB/autophagy pathway. Published databases include DrugAge to identify hits that extend lifespan, earlier published data from studies that used the LOPAC library and Cmap to identify candidates most likely involved in neurodegeneration pathways.
As a proof of principle, we will test whether the identified candidates improve progeroid phenotypes in vitro at the end of the grant period. Finally, these candidates will be tested in mouse models, invertebrates and human studies using internal funding or future Catalyst funding.