In the latest episode of our podcast, we delve into the fascinating world of mTOR (mechanistic target of rapamycin), a crucial protein that plays a significant role in regulating cellular processes related to growth, metabolism, and aging. The discussion is led by our host, who introduces the topic and welcomes Dr. Dudley Lamming, a prominent researcher in the field of aging and metabolism. Dr. Lamming serves as an associate professor and vice chair for biomedical research at the University of Wisconsin's Department of Medicine, where he focuses on the biology of aging and its implications for health and longevity.
mTOR is a central player in nutrient sensing and cellular signaling. It helps the body respond to nutrient availability, influencing processes such as:
Understanding mTOR is vital for exploring its impact on aging and healthspan—the period of life spent in good health.
Dr. Lamming elaborates on the role of mTOR, noting that it is activated in response to nutrients, particularly amino acids from protein. When mTOR is active, it promotes growth and metabolism, but this can have negative consequences if it remains overly active, especially in the context of aging. High mTOR activity is associated with various age-related diseases, including:
Dr. Lamming explains that in his research, animals subjected to fasting—specifically, those that eat one meal a day—experience significant metabolic benefits. These animals fast for approximately 21 hours each day, leading to:
Fasting appears to be essential for some of the benefits associated with caloric restriction, which has been shown to extend lifespan in various organisms. Interestingly, studies suggest that fasting alone can lead to metabolic improvements and potentially extend lifespan by about 10%.
The host inquires about different fasting regimens, such as the 16:8 method, where individuals fast for 16 hours and eat during an 8-hour window. Dr. Lamming shares that research has explored various feeding paradigms, including:
The discussion then transitions to rapamycin, a well-known mTOR inhibitor. Dr. Lamming describes rapamycin as a compound discovered in the late 1960s, initially used as an immunosuppressant in organ transplantation. It inhibits mTOR signaling, which has been shown to extend lifespan in mice by 10% to 25%, regardless of age.
While rapamycin is effective in extending lifespan, it also has side effects, particularly related to mTOR complex 2 (mTORC2), which can lead to issues like:
The challenge lies in finding the right balance in dosing:
The host raises the topic of metformin, a common diabetes medication, and its influence on mTOR. Dr. Lamming explains that metformin primarily activates AMPK (AMP-activated protein kinase), which works oppositely to mTOR. When energy levels are low, AMPK is activated, leading to reduced mTOR activity. This mechanism contributes to metformin's effectiveness in:
While metformin has been shown to extend lifespan in individuals with type 2 diabetes, its effects on those without diabetes remain unclear. Some mouse studies have suggested potential lifespan extension, but results are mixed.
As the conversation progresses, the host asks Dr. Lamming for practical steps that listeners can take to influence mTOR activity positively. Dr. Lamming suggests several strategies:
In closing, the host expresses gratitude to Dr. Lamming for sharing his insights on mTOR, fasting, and the implications for health and longevity. The episode highlights the importance of understanding mTOR's role in aging and offers practical advice for listeners looking to enhance their healthspan and potentially extend their lifespan through lifestyle changes.
This enlightening discussion underscores the intricate relationship between diet, fasting, and cellular signaling pathways, providing a roadmap for individuals interested in optimizing their health through informed choices.
