DNA Damage, Senescence & Apoptosis | 48 - Aditi Gurkar

Subscribe to our channel: https://www.youtube.com/@optispan Check out the Gurkar lab: http://agresearchlab.com/ In May 2024, Matt delivered a talk at the 2024 Glenn AFAR Grantee Conference in Santa Barbara, California and met with several people doing interesting work in the longevity field. One of these was Aditi Gurkar, an assistant professor in the University of Pittsburgh's Aging Institute, Division of Geriatric Medicine whose lab focuses on the downstream effects of DNA damage on aging. Prior to setting up her lab at the University of Pittsburgh, Aditi conducted research on the impact of DNA damage on aging at Scripps Research. She also completed postdoctoral training at Massachusetts General Hospital/Harvard Medical School and the Broad Institute of MIT and Harvard, where she focused on the tumor suppressor p53 as well as on autophagy regulation. Aditi received a PhD and a B.S. from the Boston University School of Medicine and Florida International University in Miami respectively. Matt and Aditi spend much of this episode chatting about senescent cells: how Aditi developed a focus on cellular senescence and found its relevance to aging, potential therapeutic benefits of senescent cell clearance, and the much-debated question of how to define a senescent cell. They also discuss the importance of "zooming out" from narrow areas of focus in the geroscience field to find new solutions and of breaking your own models on your way to productive new directions in science. 0:00 Introduction 1:11 How Aditi became interested in the biology of aging 8:04 Some people say that the potential impact of reprogramming is small because the DNA damage is permanent: Aditi's take 11:52 How do you differentiate between cellular senescence and apoptosis? 13:08 Cellular senescence and lipid mediators that may drive inflammation 16:06 Aditi's early work in cellular senescence + why senescence happens 19:03 How can we define a senescent cell? 22:15 Reprogramming senescent cells 24:20 The different flavors of senescent cells 26:20 New tools to explore cellular senescence 34:38 Will clearing senescent cells have large therapeutic benefits for life- and/or healthspan? How effective have the senolytics tested so far in animal models been at clearing senescent cells? 39:45 Is exercise a senolytic? 41:36 Why do some people believe that senescent cells don't exist? 46:55 The most compelling evidence that DNA damage is a causal mechanism of aging 53:27 Does cellular senescence happen in C. elegans? 56:15 Matt summarizes his talk: reflections on a quarter-century of aging biology 1:05:10 Wrapping up Producers: Tara Mei, Nicholas Arapis Video Editor: Jacob Keliikoa DISCLAIMER: The information provided on the Optispan podcast is intended solely for general educational purposes and is not meant to be, nor should it be construed as, personalized medical advice. No doctor-patient relationship is established by your use of this channel. The information and materials presented are for informational purposes only and are not a substitute for professional medical advice, diagnosis, or treatment. We strongly advise that you consult with a licensed healthcare professional for all matters concerning your health, especially before undertaking any changes based on content provided by this channel. The hosts and guests on this channel are not liable for any direct, indirect, or other damages or adverse effects that may arise from the application of the information discussed. Medical knowledge is constantly evolving; therefore, the information provided should be verified against current medical standards and practices. More places to find us: Twitter: https://twitter.com/optispanpodcast Twitter: https://twitter.com/optispan Twitter: https://twitter.com/mkaeberlein Linkedin: https://www.linkedin.com/company/optispan https://www.optispan.life/ Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it. On this podcast I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these episodes helpful!