Catalyst Awardee

Project Description

DNA methylation status in human pancreatic islets as a function of biological metabolic health

Adrian Teo | IMCB – Institute of Molecular and Cell Biology; Brian Kennedy | NUS
Competition Sponsor: Ministry of Health and National Research Foundation of Singapore
Awardee year: 2023

Ageing is a major risk factor for diabetes, with one in three elderly Singaporeans having diabetes. However, the link between ageing and beta cell failure in diabetes remains unclear. Increasingly, there is substantial evidence pointing to epigenetic alterations that are associated with ageing, giving rise to age-related diseases. A small number of studies have started to evaluate the link between DNA methylation in islets and diabetes in ageing. However, the studies suffered from low sample size or lack of tissue-specificity. Here, we hypothesise that as pancreatic islets age, key functional genes are differentially methylated, altering gene expression and metabolic function/health. We aim to 1) determine the DNA methylation status of human pancreatic islets and their correlation with chronological age, and 2) correlate the transcriptome of human pancreatic islets with DNA methylation status and identify key beta cell genes that are dysfunctional with ageing, leading to beta cell functional decline. Using machine learning, we will derive an islet-specific algorithm (epigenetic clock) to predict beta cell biological age and metabolic health of an ageing individual. We will also identify beta cell genes that can potentially be altered to improve beta cell functional decline in ageing. Overall, the improvement of metabolic health of ageing individuals will delay the onset of metabolic disorders such as diabetes.

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