Physiological Reviews Associate Editor Prof. Christoph Handschin speaks with Prof. Paul L. Greenhaff and Prof. Janet M. Lord about their article “Multisystem Physiological Perspective of Human Frailty and Its Modulation by Physical Activity,” published in the April 2023 issue of Physiological Reviews. Prof. Greenhaff is Professor at the School of Life Sciences at the University of Nottingham and is deputy director of the Medical Research Council (MRC)-Versus Arthritis Centre for Musculoskeletal Ageing Research. Prof. Lord is Professor at the Institute of Inflammation and Ageing at the University of Birmingham and is the director of the MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research. Introduction of the authors [1:06] What does the term ‘frailty’ actually mean, and how is it clinically defined? [2:49] Are there specific risk factors that increase the chance of becoming frail? [5:18] What interventions are useful to guard against frailty? [6:55] How important will mechanistic aspects of frailty be in our understanding and treatment of frailty? [13:55] Are there things we can do with regard to prevention, the mindset of patients and physicians, and interventions in the clinic? [21:10] What advice do the authors have to minimize the impact of frailty, regardless of age? [23:15] The importance of remaining mentally active [25:55]  Subscribe to the podcast on Apple Podcasts, Google Podcasts, Spotify, and Amazon Music to receive immediate notification when new episodes are available. Browse recent articles on our website. Be sure to let your colleagues know about the podcast, and please rate and review it wherever you listen to it. Follow the journal on Twitter and Facebook. Listen to other podcasts produced by the American Physiological Society.