LSI Seminar Series: Targeting p21-highly-expressing cells to slow down aging process in mice
A key challenge in aging research is to extend lifespan in tandem with slowing down functional decline so that the life with good health (healthspan) can be extended. Here, we show that clearance of a small number of cells, which highly express p21Cip1 (p21high), starting from 20 months improves cardiac and metabolic function, and extends both median and maximum lifespan in mice. Importantly, by assessing health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting morbidity compression and healthspan extension. Mechanistically, p21high cells encompass several cell types, with a conserved pro-inflammatory signature. Clearance of p21high cells reduces inflammation, and rejuvenates transcriptomic signatures of various tissues to younger states. These findings demonstrate the feasibility of morbidity compression in mice, and indicate p21high cells as a therapeutic target for healthy aging.
Speaker
Ming Xu's research interest is centered on understanding the underlying mechanisms of age- and metabolism-related tissue dysfunction and diseases and finding therapeutic targets for combating these conditions. He received his bachelor degree in biological science from Fudan University, one of the top 3 universities in China, in 2004. After he received his Ph.D. from the University of Kansas Medical Center, Xu joined James Kirkland’s lab within the Robert and Arlene Kogod Center on Aging at the Mayo Clinic for postdoctoral training. In 2018, he joined the UConn Center on Aging as an assistant professor to start his independent research career.
In 2024, Xu joined University of Minnesota as an associate professor. His lab continues to employ novel animal models and human cell transplantation to study the underlying mechanisms by which senescent cells induce tissue dysfunction. He has obtained multiple NIH and foundation awards to support his research and has published multiple papers as senior corresponding author on impactful journals. His long-term career goal is to contribute as a basic scientist to the discovery and validation of interventions to enhance healthspan and lifespan in aging populations.