In response to several requests from listeners, we have as our guest today, Dr. Matt Kaeberlein, a professor of pathology at the University of Washington. Matt is well-known for his investigations into the basic mechanisms of aging. Much of his research in this area is focused on identifying interventions that promote healthspan and lifespan. In today’s interview, we talk to Matt about the biology of aging and what he has learned about slowing the aging process.  In 1999, Matt and his colleague Mitch McVey discovered that overexpression of the SIR2 gene is sufficient to extend lifespan in yeast. SIR stands for silent information regulator, and we have an interesting discussion about how Matt’s research and 1999 discovery have elevated SIR2 to the forefront of aging research. Also, some of Matt’s most recent and fascinating investigations have been into rapamycin, the only known pharmacological agent to extend lifespan.  His research has shed new light on the role rapamycin plays in delaying age-related dysfunction in rodents, dogs, and humans. We also have a fun discussion with Matt about his research showing that rapamycin may have the potential to reduce the mortality of companion dogs. The paper that came out of this research landed Matt on the front page of the New York Times and received prominent play in the national and overseas media. Other topics we cover include: Matt’s attempts to uncover the molecular mechanism behind lifespan extension via calorie restriction. His research into mTOR, which is a protein in every cell, and how inhibiting mTOR has been shown to extend the lifespan of insects, rodents, and animals. Matt’s 2006 study that showed fasting extends lifespan in worms more than caloric restriction. And an article Matt published last year that summarized several of the most popular anti-aging diets, comparing them with classical caloric restriction. In addition to his work in his Kaeberlein Lab, Matt is the co-director of the Nathan Shock Center of Excellence in the Basic Biology of Aging and the founding director of the Healthy Aging and Longevity Research Institute at the University of Washington. He also is the founder and co-director of the Dog Aging Project. Show notes: [00:02:53] Dawn asks Matt and his youth and where he grew up. [00:03:06] Ken asks if it is true that Matt spent a good deal of his youth “up to no good.” [00:04:20] Dawn mentions that while Matt got decent grades in school, it wasn’t until he went to college that he became studious. Dawn asks Matt if it true that he had originally decided to skip college. [00:05:42] Dawn asks how Matt ended up in Bellingham at Western Washington. [00:06:41] Dawn asks how in the world, despite not liking high school and working a morning shift at UPS for two years after graduating, Matt decided to head off for college and major in biochemistry of all things. [00:08:01] Ken asks what led Matt to travel across the country to Boston and MIT’s biology program. [00:09:57] Ken asks why Matt decided to focus his research on the biology of aging. [00:11:57] Matt talks about what he did following his Ph.D. [00:13:15] Dawn asks Matt what kind of research he did at the University of Washington Department of Genome Sciences for his post-doc, and how this research related to aging. [00:15:10] Ken mentions that it was during Matt’s undergrad that he decided to focus on the question, “To what extent are the mechanisms of aging evolutionarily conserved?” Ken asks Matt what caused him to arrive at that for his central focus. [00:19:36] Dawn mentions that the discovery by Matt, and Mitch McVey, that overexpression of SIR2 (Silent Information Regulator) is sufficient to extend life span in yeast is credited with promoting SIR2 to the forefront of aging research. Dawn goes on to mention that SIR genes are determinants of life span in yeast mother cells. Dawn asks Matt to give a quick primer on the SIR genes a...