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Recent studies highlight the role of specific longevity agents like rapamycin in slowing the aging process in animal models. Namely, scientists believe that rapamycin, proper nutrition, and caloric restriction may slow down the aging process in animal models and may be transferable to human health.
In the latest episode of Longevity by Design, our co-hosts, Dr. Gil Blander and Ashley Reaver, are joined by Dr. Matt Kaeberlein, Professor at the Department of Laboratory Medicine and Pathology at the University of Washington. Tune in as Dr. Matt Kaeberlein describes the longevity agent rapamycin and its impact on mTOR and the Dog Aging Project, which is investigating companion dogs as a model organism for aging.
Meet Longevity by Design’s podcast guest, Dr. Matt Kaeberlein
Dr. Matt Kaeberlein is a Professor at the Department of Laboratory Medicine and Pathology at the University of Washington. He has published over 200 scientific papers and has received several prestigious awards. His work has also been recognized with Fellow status in the American Association for the Advancement of Science, the American Aging Association, and the Gerontological Society of America. Dr. Matt Kaeberlein is best known for his research focused on basic mechanisms of aging and their connection with lifespan and quality of life.
In his first year of college, Dr. Matt Kaeberlein recounts having a fantastic biology teacher who turned him on to the subject. Intending to pursue a graduate degree in structural biology, Dr. Matt Kaeberlein attended Dr. Lenny Guarente’s seminar during his first year in graduate school. He talked about how his lab was using genetics and molecular biology to study the biology of aging. Understanding a field as complex as the biology of aging inspired Dr. Matt Kaeberlein to pursue his Ph.D. with Dr. Lenny Guarente, and his passion for the field of aging grew.
What are the differences between lifespan and healthspan?
While there are varying definitions of healthspan, Dr. Matt Kaeberlein defines healthspan as “The period of life spent free of chronic disease and disability—a period of life spent in good health.”
While Dr. Matt Kaeberlein believes that healthspan is a useful concept, he discusses how it should be interpreted with caution, “When we talk about the effect of interventions or genetic manipulations on health, we need to be precise about what we mean. There is no agreed-upon assay or set of metrics to quantify healthspan. Lifespan is a quantitative value.”
Does activating sirtuins impact aging?
When it comes to the impact of sirtuins on the aging process, Dr. Matt Kaeberlein also recommends interpreting the data with caution. "I think the biology that sirtuins are involved in is important, and they're involved in lots of different cellular processes that intersect with aging." He agrees that SIRT6 is the sirtuin that looks the most promising because activating SIRT6 can positively affect lifespan and healthspan in the labs.
How does inhibiting mTOR impact aging?
mTOR is the major regulator of growth in animals. mTOR is activated by oxidative stress, which humans aim to avoid. Therefore, drugs that target mTOR inhibition may delay the aging process.
Dr. Matt Kaeberlein is particularly passionate about the impact that the agent rapamycin can potentially have on mTOR and thus aging. "Rapamycin is a small molecule inhibitor of mTOR, and it has been shown to extend lifespan in yeast, worms, flies, and mice. In addition, many other studies confirm that rapamycin is also associated with various improved healthspan metrics in mice."
"Rapamycin is like the DAF-2 of C. elegans—it works robustly. It gives me a ton of confidence that there's something real here."
"Rapamycin seems to broadly impact health across lots of different tissues and organs in a mouse during aging, and it seems to be impacting healthspan, not just one disease or lifespan."
The Dog Aging Project
The evidence on the impact of rapamycin for inhibiting mTOR in mice inspired Dr. Matt Kaeberlein to explore this agent’s impact on man's best friend.
Dr. Matt Kaeberlein is the co-director of the Dog Aging Project. The goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence aging. The study aims to use this information to help pets and people increase healthspan, the period of life spent free from disease.
"There are two components to the Dog Aging Project. The largest component is a longitudinal study of aging. We're following pet dogs living with their owners throughout their lives and trying to understand the most important genetic and environmental determinants of health outcomes during aging. Every year we get metabolome, epigenome, fecal microbiome data, and medical records from their veterinary exams."
The other part of the Dog Aging Project is a clinical trial of rapamycin, Test of Rapamycin in Aging Dogs (TRIAD). The goal of TRIAD is to answer the question, 'Does rapamycin increase lifespan and improve health outcomes during aging in dogs?' Tune in to the full episode to learn more about what researchers have learned from this study so far.
Inflammation and aging
On the relationship between inflammation and aging, Dr. Matt Kaeberlein talks about how humans can apply a specific principle learned from animal studies. "If there's one thing you can fix in an aging dog or an aging person, or even an aging mouse, fixing chronic sterile inflammation is going to have a big impact systemically on the function of different tissues and organs."
Dr. Matt Kaeberlein describes one well-studied way to decrease inflammation in mice, "There's tons of evidence that caloric restriction is effective at tamping down on the increase in age-related inflammatory signals in mice." He speculates that while a 30% decrease in caloric intake is not sustainable for most humans, practicing intermittent fasting can mimic some of these results.
Advice on living a healthier longer life
There’s one thing in particular that Dr. Matt Kaeberlein aims to do every single day for longevity: "Regular exercise works well for me. And since I started exercising regularly, my physical health has improved dramatically. My mental health has improved dramatically, and I can see it in all sorts of little ways.”
Dr. Matt Kaeberlein understands that the best interventions for each person are truly personal to them. “It's important for people to figure out what works for them. It's your genetics. It's your environment. It's your lifestyle. It's your family. It's your job. So, figuring out what you can do that works for you is really important."
