Gordon Lithgow, Ph.D. on Protein Aggregation, Iron Overload & the Search for Longevity Compounds

Dr. Gordon Lithgow of the Buck Institute for Research on Aging tells us about worms! Well, more accurately, his lab does research on nematodes, particularly an animal known as C. elegans. This unassuming scientific model has a lot of important advantages for science: they can be frozen and subsequently thawed and retain viability, they are extremely well understood down to the precise number of cells in their body and the wiring of their nervous system, known as the connectome. Additionally, they have a short lifespan and are cheap to work with. Why would that be advantageous, you may ask? This is where Dr. Lithgow's work on the Caenorhabditis Intervention Testing Program comes in. Short-lived organisms give Dr. Lithgow and his colleagues the opportunity to see how their biology responds to compounds in different contexts and to do so cheaply and rapidly. Think a vitamin, pharmaceutical or one of any number of other compounds may have a broad effect on longevity? Try it on Caenorhabditis first! Taking this approach allows the broad screening of compounds that might not otherwise get its chance in the limelight if science were limited to only working with rodents, for example. But what could nematodes possibly have in common with us? The answer to the question is... gene homology! In fact, around 35% of C. elegans genes have a corresponding human version. In this over 40-minute long conversation with professor Dr. Gordon Lithgow, we talk about... Nematodes... especially C. elegans, of course! The synergistic way in which research in lower organisms (C. elegans in this case) works together with rodent research to better understand the biology of aging and identify potential therapeutics. The story behind the Caenorhabditis Intervention Testing Program, a multi-institutional effort using the advantages of C. elegans short lifespan to screen for potential compounds that may increase lifespan. We also discuss the more expensive-but-closer-to-humans version of this program known just the Intervention Testing Program. The various qualities of C. elegans, especially as related to science's deep knowledge of the organism, that make it a perfect fit for this type of research. Some of the early experiences that actually lead to my early interest in the aging field and how it actually holds a bit in common with Gordon's story today. The role of protein aggregation as a possible fundamental mechanism of aging... even beyond its more established role in neurodegenerative diseases. Some of the fascinating research surrounding mild heat stress as a means to increase lifespan in lower organisms. Some of Gordon's research into the effects of metal accumulation, particularly iron, on aging in lower organisms and how, in humans, it may be important to approach the intake of these minerals with care. The interplay between genes that influence iron-binding and the development of Alzheimer's disease. Some of Gordon's research into the (perhaps surprising) effect of vitamin D on aging in C. elegans and, particularly, on the solubility of proteins... the loss of which is a feature of aging of particular interest. The critical involvement of the Nrf2 stress-response pathway in conferring benefits of vitamin D in worms... a pathway many of you may know about from previous discussions of sulforaphane, a robust activator of Nrf2 in humans. Some of the challenges encountered with ensuring standardization of protocols across all of the participating labs in the Caenorhabditis Intervention Testing Program. The amazing genetic diversity represented in soil-dwelling nematodes and how this is also an advantage in longevity research. The interesting possibility that certain compounds may have a different overall effect on lifespan or healthspan that is dependent within certain contexts (e.g. environmentally stressed or not). Learn more about Dr. Gordon Lithgow. Did you enjoy this podcast? It was brought to you by people like you! Click here to visit our crowdsponsor page where you can learn more about how you can support the podcast for as little or as much as you like. Have you done a 23andMe genetic test? You can learn more about whether you have some of the specific polymorphisms discussed in this podcast, including ones related to the hemochromatosis and transferrin genes, by clicking here.