Catalyst Awardee

Project Description

Deciphering Aging-Dependent Human Neuronal Activity Changes, Tissue Microenvironment and Gene Expression Patterns

Jai S. Polepalli, M.A.S., Ph.D., National University of Singapore; Thameem Dheen, Ph.D., National University of Singapore; Vincent Nga Diong Weng, M.B.B.S., M.R.C.S., F.R.C.S.Ed (Surgical Neurology), National University Hospital; and Yeo Tseng Tsai, M.B.B.S., Fellowship of Royal Australasian College of Surgeons (Neurosurgery), National University Hospital

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

The aging-related decline in brain function is attributed to changes in gene expression patterns, molecular, cellular and synaptic function of the various types of cells – encompassing changes in biophysical properties of neurons and neuronal communication through synapses. This proposal aims to address the question of how changes in neuronal activity, gene expression patterns and cellular function in the human brain correlate with mental aging, and how these changes are exaggerated in pathological conditions. The idea central to this proposal is that examining and correlating changes in the structural, functional and genetic profiles of the human brain will enable us to identify human brain-specific molecular markers of mental aging. This identification (of molecular markers of aging) will advance drug discovery targeted towards delaying and slowing the mental aging process. To achieve the objectives of this proposal, we will perform experiments on fresh cortical tissue extracted from neurosurgery patients of different age groups, at the National University Hospital- Singapore during routine surgical procedures. We will employ a combination of tools in single-cell RNA sequencing, in-vitro electrophysiology, and neurochemistry. This combination of approaches is being employed for the first time to study human mental aging.

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

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