Aging & Gerontology

Abstract

Aging is the primary risk factor for cardiovascular and metabolic disease, and by 2030, one-third of the global population will have some form of these diseases threatening the healthspan. One potential cause of cardiovascular aging is endothelial cell senescence. While endothelial senescence is known as a bona fide risk for aging-associated diseases, much remains unknown about the intrinsic origins and rescue strategies. Perivascular adipose tissue (PVAT) is an important neighboring tissue that actively contributes to vascular dysfunction in aging. Recent research reveals that endothelial cells and PVAT interact through their senescence-messaging secretomes. So, what promotes senescence in one of these cell types can stimulate cellular senescence and dysfunction in the other one. Multiple initiating triggers, namely gut microbiota-derived metabolites, have been identified to drive oxidative stress, a major hallmark of cellular senescence, and regulate oxidative-regulated host genes involved in the biology and function of endothelial cells and perivascular adipocytes. We recently discovered that aging-related microbiota alterations negatively impact redox and energy homeostasis and thereby cause senescence in these cells. Methylamines and uremic toxins increase intracellular hydrogen peroxide generation, which thereby induces cellular pathways and epigenetic alterations leading to senescence and proliferative arrest. To rescue cellular senescence, we employed a metabolite-based approach to restore redox homeostasis and epigenetic mechanisms. Our findings reveal new roles of gut microbiota in (peri)vascular aging and provide new insights into senescence-escape therapies to restore youthful-like (peri)vascular function and to expand lifespan.  
 

Biography

Dr. Soheil Saeedi, PharmD, PhD, Group Leader and Head of the Cardiovascular Aging Lab at the Center for Translational and Experimental Cardiology (CTEC), University of Zurich, received his PhD in 2016 from Tehran University of Medical Sciences (TUMS), followed by postdoctoral fellowships at Harvard Medical School and University of Zurich. His research areas include cardiovascular aging and redox biology. He has authored or co-authored over 60 peer-reviewed publications in first-line journals, namely European Heart Journal, Proceedings of National Academy of Sciences USA, and Aging Cell. He also edited 8 peer-reviewed books and chapters and presented research work at over 30 international conferences. He has served as editorial board and reviewer of >20 prestigious journals e.g., European Heart Journal, and professional member of over 10 international scientific associations, including the American Heart Association (AHA), European Society of Cardiology (ESC), and European Atherosclerosis Society (EAS). He has been honored with numerous international and national awards (>25 prizes), namely, including "Paul Dudley White International Award" from the American Heart Association (2021 & 2022), "Early Career Research Award" from International Society of Thrombosis and Hemostasis 
(ISTH, 2023), "AGLA Walter Riesen Award" from the Swiss Atherosclerosis Association (2021), 
"European Atherosclerosis Society Young Investigator Fellowship" (2021-2023), "FAN Fellowship Award" and "DOCR Award" from University of Zurich (2022), and "Harvard Fellowship" (20172019).