Prof Hiu Tung Tom CHEUNG, PhD | Division of Life Science, HKUST-Nan Fung Joint Laboratory, State Key Laboratory for Molecular Neuroscience, Molecular Neuroscience Center, Biotechnology Research Institute, The Hong Kong University of Science and Technology, Hong Kong, China;
Competition Sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China
Award Year: 2023
The rich phenotypic diversity of the human population demonstrates how genetic variation influences lifespan and healthspan. Aside from environmental factors, genetic factors play a role in disease development and aging. Indeed, aging research has largely focused on genetic variants affecting the cell state, leading to specific disease phenotype manifestations. Still, little is known about the variants contributing to healthy aging. We propose to explore genetic complexity and its role in healthy aging by identifying novel genetic variants conferring high resilience to various cellular stresses, using a genetically diverse mouse resource engineered to recapitulate the genetic richness of the human population. Muscle stem cells (MuSCs, also known as satellite cells, SCs), the adult stem cells responsible for muscle regeneration, will be studied as a proof of concept. SCs turn over slowly and remain in quiescence, a reversible G0 state, until receiving stimuli to activate and contribute to myogenic lineage progression. However, during aging, MuSCs lose their stem cell resilience (e.g., the capacity to respond to cellular stresses, maintain quiescence, and rapidly activate), leading to a loss of SC functions and numbers as muscle ages. Hence, SCs serve as an ideal stem cell model of aging. Here, we will first conduct transcriptomic and epigenetic analysis on SCs isolated from genetically distinct mouse strains subjected to various cellular stresses. Such approaches will identify unique genetic variants conferring a healthy aging phenotype, serving as a novel therapeutic target to improve the organismal healthspan.