In this episode of Longevity by Design, hosts Ashley Reaver, MS, RD, CSSD, and Dr. Gil Blander sit down with Dr. Gordon Lithgow, a Professor and Vice President for Academic Affairs at the Buck Institute for Research on Aging. Dr. Lithgow's research focuses on understanding the mechanisms of aging and identifying genes and small molecules that can prolong lifespan. With a background in genetics from the University of Glasgow and extensive experience in biotechnology and aging research, Dr. Lithgow shares his journey from growing up in Scotland to leading a lab at the Buck Institute.

Dr. Lithgow discusses the compelling nature of aging as a profound biological mystery, which drew him into the field. He highlights his lab's approach of following curiosity-driven research, often using the nematode worm C. elegans as a model organism due to its short lifespan and genetic similarities to humans. This unbiased method has led to significant discoveries, including genetic mutations and drug-like molecules that extend lifespan. The conversation also covers the concept of geroscience, which Dr. Lithgow helped coin, emphasizing the link between aging and chronic diseases.

A major focus of Dr. Lithgow’s work is studying protein homeostasis, which declines with age. Protein misfolding is implicated in many age-related diseases; that discovery moved the lab’s focus from lifespan extension to efforts to understand drivers of healthspan and the causes of age-related chronic diseases, in particular Alzheimer’s and Parkinson’s. His work also includes the influence of environmental factors, such as mild heat stress, and dietary iron, vitamin D, and alpha-ketoglutarate (AKG) on aging. Dr. Lithgow's interdisciplinary collaborations aim to uncover new interventions to extend healthspan and longevity.

Dr. Gordon Lithgow is also the host of Buck Institute for Research on Aging's podcast, "We're not getting any younger... yet" on which he speaks with some of the brightest scientific stars on the planet to search for—and actually find answers to—questions on aging. The podcast can be found at https://www.buckinstitute.org/podcasts/ and on podcast apps.

Episode timestamps

• Introduction: 00:00-02:42
• What led Dr. Gordon Lithgow to become a scientist and research the biology of aging?: 02:43-06:20
• Why are worms (C.-elegans) a good model for studying aging?: 06:21-07:55
• Why did Dr. Gordon Lithgow transition from research investigating ways for extending lifespan to extending healthspan?: 07:56-09:24
• What specific diseases is Dr. Gordon Lithgow researching?: 09:25-12:01
• What does protein shape mean for aging?: 12:02-13:12
• How does mild heat stress impact health and aging?: 13:13-16:35
• How does vitamin D and alpha-ketoglutarate impact aging, healthspan, and lifespan?: 16:36-25:26
• How does dietary iron impact aging, healthspan, and lifespan?: 25:27-29:57
• Are there more genes and proteins to be discovered that influence aging, or have they all been discovered?: 29:58-34:12
• What compound do you think has the most potential for extending healthspan and lifespan?: 34:13-35:54
• What is the impact of calorie restriction and exercise on healthspan and lifespan in humans?: 35:55-38:51
• What is the importance of clinical trials for aging research?: 38:52-42:09
• What are the future directions of Dr. Gordon Lithgow’s research?: 42:10-43:38
• Dr. Gordon Lithgow’s top tip for living better longer?: 43:39-48:50