Rochelle Buffenstein is one of the world’s leading authorities on the naked mole rat, a fascinating animal that has emerged as an important model for research in longevity science. Dr. Buffenstein is currently a senior principal investigator at Calico Life Sciences, a subsidiary of Alphabet, that is seeking to better understand the biology that controls aging and lifespan. Today Dr. Buffenstein joins host Bob Hughes to explain why the naked mole rat is such a powerful model of successful aging. She talks about their resistance to cardiovascular disease, cancer, and neurodegeneration, and what this means for improving human health. You’ll hear about the role of Nrf-2 signaling in maintaining optimal health, looking beyond common animal model systems to understand aging more deeply, and the advantages of looking at health and longevity in naked mole rats versus mice. Dr. Buffenstein also discusses the typical hallmarks of aging and inflammation as they present in the naked mole rat, their unusual reproductive activity, and what this can teach us about human fertility. In this episode, you’ll learn why this unique and resilient creature is a “super organism” of sorts, and why Dr. Buffenstein believes they contain the blueprint for how to live long and successfully healthy lives. Episode Highlights: Introduction to naked mole rat as a powerful model of successful aging How Dr. Buffenstein came to study these animals and what is unique about their aging process Naked mole rat’s reduced susceptibility to cardiovascular disease and cancer Research on whether they are resistant to neurodegeneration Central mechanism that provides generalized protection may be at play Nrf-2 signaling pathway and its role in maintaining optimal health Thinking beyond common model systems to learn about molecular processes of aging Studying aging in a long-lived system is more pertinent to humans Advantages of looking at slow aging process in a natural context The Methuselah Mouse Prize (Mprize) is being offered to the first person who can make mice live longer than five years Ultimate cause of death in naked mole rats is unknown Hallmarks of aging and inflammation process as they relate to naked mole rat Naked mole rats lack natural killer cells, which are very important for fighting viruses Innate and adaptive immune systems Unusual reproductive activity for naked mole rats They have adapted to a particularly harsh and hostile environment Dr. Buffenstein believes they contain the blueprint for how to stave off many of the adverse effects of aging Quotes: “A naked mole rat is a mouse-sized rodent that stands out as an especially powerful model of successful aging, primarily because it is known to live an incredibly long time. It seems to be exceptionally resistant to most age-associated diseases like cancer and cardiovascular disease. And even reproductive senescence.” “We believe that given this phenotype that these animals are a very good example that aging does not need to be inevitable, and that they hold the blueprint for how to live long and successfully healthy lives.” “I got my first grant, looking at how it is that they're able to live 17 years. Little did I know then that these animals would be exceeding 39 years of age in my care.” “The fact that these animals don't seem to show any age-related change in cardiac function to me is remarkable. If we could understand the mechanism behind that, we might be able to come up with ways to improve human heart function and human health.” “[Naked mole rats] seem to be resistant to just about everything.” “We think that the mechanisms that protect them against aging might be the same as some mechanisms that protect them against cancer as well.” “We know that broccoli and the cruciferous vegetables all upregulate Nrf-2 naturally.” “I think the traditional model organisms have played a very important role in understanding