Matt Kaeberlein on Rapamycin Longevity Series | Lessons learned from two decades of Rapamycin research
May 15, 2023
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Matt Kaeberlein, a leading Rapamycin researcher, discusses insights on mTOR, longevity, immune modulation, Dog Aging Project, effects on aging hallmarks, side effects of interventions, biomarkers for health assessment, personal experimentation, and future of longevity research.
Rapamycin extends lifespan by inhibiting mTOR, mimicking caloric restriction to reshape aging biology.
Rapamycin impacts mitochondrial dysfunction and senescent cells, emphasizing its potency in certain aging areas.
Rapamycin boosts immune responses, rejuvenating aged immune systems and challenging conventional immune decline beliefs.
The Dog Aging Project studies canine aging factors, influencing human aging research with large-scale interventions.
Dog Aging Project promotes open science, involving community in aging research and bridging dog-human aging studies.
Research on caloric restriction and meal timing effects in mice influences potential insights for human longevity.
Deep dives
Research on Rapamycin and Aging
Rapamycin, an mTOR inhibitor, was discovered to extend lifespan through yeast genetic screens. The identification of TOR1 deletion mutants led to a hypothesis that mTOR inhibition could mimic caloric restriction, paving the way for longevity research. Genetic screens in yeast, worms, and flies converged on mTOR as a key regulator of lifespan. Rapamycin, by inhibiting mTOR, extended lifespan across multiple model organisms, a landmark discovery reshaping aging biology.
Rapamycin's Impact on Hallmarks of Aging
Rapamycin's effects on aging hallmarks are varied, with significant impacts on mitochondrial dysfunction and senescent cells observed. While the drug influences all hallmarks of aging to some extent, its potency is more pronounced in certain areas like mitochondrial health. The evolving definition of aging hallmarks underscores the intricate interplay between rapamycin and age-related cellular processes, emphasizing its multi-faceted impacts on the aging phenotype.
Rapamycin's Role in Immune Modulation
Rapamycin's immune-modulating properties stood out in research, showcasing its ability to enhance immune responses rather than suppress them. Studies on aged mice and flu vaccine responses revealed rapamycin's potential to rejuvenate aging immune systems, challenging the notion of immune decline with age. By modulating sterile inflammation and targeting autoimmune processes, rapamycin exhibited a unique immune-boosting effect that defied conventional expectations.
Dog Aging Project: Unraveling Canine Aging
The Dog Aging Project embarks on two significant goals: unraveling genetic and environmental factors influencing canine aging in a large-scale longitudinal study, and conducting a clinical trial to evaluate rapamycin's effects on lifespan and health span in companion dogs. With almost 45,000 dogs in the longitudinal study, the project explores both observational discoveries and interventions to address aging in dogs, pioneering research that could shed light on aging biology in companion animals.
Contribution to Understanding Dog and Human Aging
The Dog Aging Project not only illuminates the intricacies of canine aging but also offers insights into human aging. By investigating genetic, environmental, and therapeutic influences on companion dogs' aging process, the project contributes valuable data to inform parallel studies in human aging. Through an open science approach, sharing data with the public and inviting collaborations, the project bridges the gap between dog and human aging research, fostering scientific advancements in the field.
Unique Aspects of the Dog Aging Project
The Dog Aging Project emphasizes open science and community involvement, distinguishing itself with its approach. It encourages community science with dog owners actively participating in data collection, engaging the public in scientific research and the biology of aging through their pets.
Examining Time-Restricted Eating in Relation to Longevity
Research on caloric restriction's impact on longevity in mice led to investigations about intermittent fasting and time-restricted feeding. Studies suggest that benefits may be tied to caloric restriction rather than the timing of meals alone. There's ongoing exploration into the longevity effects of varying meal timings and caloric intake in mice and potential extrapolation to humans.
Frequency of Dog Feeding and Age-Related Diseases
Analyzing data from the Dog Aging Project revealed that dogs fed once a day showed a lower likelihood of age-related disease diagnoses compared to those fed more than once a day. This association was particularly significant in several categories of age-related disorders, indicating that feeding frequency may impact disease risk in dogs.
Lessons from Self-Experimentation with Rapamycin
Self-experimenting with rapamycin led to personal insights and positive experiences. While acknowledging the biases inherent in self-experimentation, the benefits observed included reduced inflammation and functional improvements. The individual's deepened understanding and firsthand experience highlighted the practical application and potential benefits of a drug like rapamycin.
Research on Longevity Interventions
Longevity interventions like metformin and NAD precursors have shown promising results in human studies despite mixed data in mice. Metformin is found to be protective in diabetics against mortality and age-related diseases, but its benefits for non-diabetics are uncertain. NAD precursors may benefit individuals with NAD homeostasis challenges in specific tissues like brain and muscle. The efficacy and risks of these interventions remain unclear, calling for more research to understand their broader impacts on aging biology.
Exploring Combinatorial Longevity Interventions
Investigating combinations of longevity compounds reveals intriguing interactions that could potentially lead to significant health benefits surpassing known interventions like rapamycin. Research efforts focus on understanding how different longevity interventions interact and affect aging biology. The development of a high-throughput longevity analysis technology aims to explore a vast landscape of intervention combinations for enhanced longevity outcomes. This platform allows for extensive experimentation to uncover synergistic or additive effects of various interventions on lifespan and health.
Professor Matt Kaeberlein from the University of Washington is one of the world's leading researchers in the Rapamycin field. He has done Rapamycin research on multiple species for two decades. Everything from yeasts, worms, mice and now also dogs and humans. Matt has made a big contribution to the longevity field and in this podcast he will share the knowledge he has acquired in the field.
Disclaimer: The podcast is for general information and educational purposes only and is not medical advice for you or others. The use of information and materials linked to the podcast is at the users own risk. Always consult your physician with anything you do regarding your health or medical condition.
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