Catalyst Awardee

Project Description

Small RNAs: Big Answers to Healthy Longevity?

Hataitip Tasena, M.Sc., Ph.D., Brian Kennedy, Ph.D., Yvonne Tay, Ph.D., and Maximilian Unfried, M.Sc., National University of Singapore

Competition Sponsor: Ministry of Health and National Research Foundation of Singapore

Humans have long been searching for the path to longevity. Among the latest but less known possibilities being proposed is PIWI-interacting RNAs (piRNAs). These small non-coding RNAs could prevent DNA damage and genomic instability, ones of the key hallmarks of aging and significant players in various age-related diseases.

The main function of piRNAs is transposon silencing. A piRNA guides a PIWI protein to its DNA target, including a transposon, resulting in transcriptional repression through epigenetic modifications or by inducing post-transcriptional mRNA degradation. Active transposons, known to increase with age, can lead to aberrant gene expression and cause damage to genomic integrity. Meanwhile, several mRNAs associated with age have been identified. We hypothesize that piRNAs could contribute to healthy aging, possibly by suppressing transposons or other aging-related mRNAs.

Although some piRNAs associated with heart failure, cancer or Alzheimer’s disease have been identified, no study to date has reported piRNAs associated with aging. In this proposed study, we will take the first step to identify aging-associated piRNAs using the relatively inexpensive approach.

Firstly, genome-wide piRNA expression will be profiled in young (n=6) and old (n=6) mice to identify piRNAs differentially expressed with age. Next, the significant piRNAs that are also expressed in human (using online piRNA database “piRBASE” as a reference) will be shortlisted. Among these, the most differentially expressed piRNA will be overexpressed in human cells, of which genome-wide mRNA expression will be profiled to identify mRNAs potentially targeted by the piRNA. Finally, the pathway analysis will be performed on the list of mRNAs differentially expressed with the overexpressing piRNA.

This study will shed light on the potential mechanisms through which piRNAs may regulate aging. The findings will enable researchers to utilize more targeted approaches to confirm the aging-related functions of piRNAs in humans in the future.

To learn more about this proposal, email healthylongevity@nas.edu.

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