Catalyst Awardee

Project Description

Unraveling potential drug targets for longevity using sex-specific Mendelian randomization


Competition Sponsor: The Chinese University of Hong Kong and The University of Hong Kong

The gender gap in longevity highlights the potential of sex-specific etiological insights to identify more effective pharmaceutical interventions. Women generally have lived longer than men worldwide since the mid-18th century. Sex differences in chronic disease patterns, lifestyle and healthcare seeking behaviour may all contribute to lifespan discrepancy. From an evolutionary biology perspective, longevity trades off against reproduction such that maximising reproductive success may be at the expense of susceptibility to chronic diseases. Explicating underlying biological drivers of longevity separately in men and women would shed light on interventions for promoting healthy aging and longevity. This pioneering project aims to identify drivers, with a focus on potentially druggable protein targets, of longevity in men and women using sex-specific Mendelian randomization. Exploiting ‘big data’ of large extensively genotyped genetic associations using Mendelian randomization has opened up new opportunities for timely and cost-effective drug discovery and repurposing. By using genetic variants as instrumental variables to assess causal associations, Mendelian randomization provides less biased estimates to inform the causal roles of potentially druggable exposures. This work will firstly identify potentially sex-specific druggable proteins relevant to longevity in Western populations. If substantiated in Asian populations in the future, our systematic search of relevant protein drug targets for longevity would accelerate drug development tailored-made for men and women, thereby contributing to close the gender gap in longevity globally.

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