#66 - Vamsi Mootha, M.D.: Aging, type 2 diabetes, cancer, Alzheimer's disease, and Parkinson's disease – do all roads lead to mitochondria?

In this episode, Dr. Vamsi Mootha, an expert in mitochondrial biology and investigator at the Howard Hughes Medical Institute, shares his breadth of knowledge on the mitochondrion organelle: its history, function, genome architecture, and his research of rare mitochondrial dysfunction. Vamsi is currently focused on finding clinical treatments for the 300-some identified rare disorders, but in this work there is a wealth of potential implications in the context of longevity and chronic disease. In this conversation, Vamsi elucidates how the latest research could give insight into conditions related to aging, including but not limited to Alzheimer's disease, Parkinson's disease, insulin resistance and type 2 diabetes, cancer, and much more. We also explore some of the most exciting potential therapies for mitochondrial diseases such as hypoxia (oxygen deprivation), how exercise affects the mitochondria, the use of hyperbaric chambers for cancer therapy, and the mechanisms by which Metformin might confer longevity benefits in a non-diabetic individual. We discuss: <ul> <li>The Broad Institute of MIT and Harvard [8:00]; </li> <li>Vamsi's academic background [10:30]; </li> <li>Advice for college students and med students considering a career in medicine and/or medical research [15:30]; </li> <li>Vamsi's focus on mitochondria and mitochondrial disorders [20:00]; </li> <li>The mitochondrial genome: Lineage, endosymbiosis, and reductive evolution [23:15]; </li> <li>How many diseases can be attributed to mitochondrial mutations? [28:45]; </li> <li>Nuclear DNA and mtDNA: Roles, interaction, communication, and biogenesis [31:30]; </li> <li>Which cells have the most mitochondrial DNA? And how often does mitochondria turn-over in a cell? [37:30]; </li> <li>Does ALL of your mitochondrial DNA come from your mother? [40:00]; </li> <li>Mitochondria 101: The powerhouse of the cell, electron transport chain, and the NADH/NAD ratio [44:00]; </li> <li>NAD and NADH: Role in the mitochondria, decline of NAD levels with age, and what it means to age at a mitochondrial level [51:30]; </li> <li>Mitochondrial diseases Vamsi studies in his lab [55:15]; </li> <li>Mitochondria and oxygen: Poor oxygen utilization and excess oxygen contributes to the pathology seen in some of the rare mitogenic diseases [1:02:00]; </li> <li>What VO2 max can tell us about mitochondrial function, insulin resistance, type 2 diabetes, and more [1:10:00]; </li> <li>Can studying mitochondrial disease provide insights into the common forms of aging? [1:18:45]; </li> <li>Could muscle cell inflammation (a signature of aging) be caused by mtDNA damage being confused as foreign bacteria? [1:22:00]; </li> <li>Exercise and mitochondrial health: Is there an optimal exercise strategy to slow the aging process? [1:27:00]; </li> <li>What autophagy means in the context of mitochondria [1:36:15]; </li> <li>Metformin's impact on exercise and lactate levels [1:40:15]; </li> <li>How might metformin confer longevity benefits? [1:48:15]; </li> <li>Hypoxia as a potential therapeutic option for mitochondrial disease [1:52:45]; </li> <li>Cancer prevention and treatment: hyperbaric oxygen chambers, targeting single carbon metabolism of the mitochondria, and more [2:00:00]; </li> <li>Chronic diseases have altered mitochondria: Evidence for mitochondrial dysfunction causing Parkinson's disease [2:04:30]; </li> <li>Why Vamsi is very optimistic about the possibility of targeting mitochondrial proteins as therapies [2:09:30]; </li> <li>Is it theoretically possible to genetically engineer a better functioning mitochondria? [2:14:30]; </li> <li>Vamsi's fantasy experiment in an unconstrained world [2:20:15]; and </li> <li>More.</li> </ul> Learn more: <a href="https://peterattiamd.com/">https://peterattiamd.com/</a> Show notes page for this episode: <a href="https://peterattiamd.com/vamsimootha/">https://peterattiamd.com/vamsimootha/</a> Subscribe to receive exclusive subscriber-only content: <a href="https://peterattiamd.com/subscribe/">https://peterattiamd.com/subscribe/</a> Sign up to receive Peter's email newsletter: <a href="https://peterattiamd.com/newsletter/">https://peterattiamd.com/newsletter/</a> Connect with Peter on <a href="http://Facebook.com/PeterAttiaMD">Faceboo</a>k | <a href="http://Twitter.com/PeterAttiaMD">Twitter</a> | <a href="http://Instagram.com/PeterAttiaMD">Instagram</a>.

Actionable Insights

1. Hypoxia as Treatment: Extreme Caution

Do not attempt to apply hypoxia (oxygen deprivation) as a treatment in humans outside of a clinical trial setting. Current research is restricted to animal studies, and hypoxia can have life-threatening implications, making human application premature and irresponsible.

2. Prioritize Exercise for Mitochondrial Health

Engage in regular exercise, as it is one of the best ways to increase the number of mitochondria, turn over malfunctioning ones, and induce the biogenesis of healthy new mitochondria. This process acts as a ‘smart system’ that cleanses and rejuvenates the cellular energy machinery.

3. Avoid Antioxidants with Exercise

Refrain from taking antioxidants in conjunction with exercise, as studies suggest they may prevent or erase some of the beneficial adaptive effects of exercise. Reactive oxygen species (ROS) likely play an important signaling role that aids in the body’s adaptation to physical activity.

4. Optimize Lifestyle for Type 2 Diabetes

For individuals with Type 2 Diabetes (excluding late-stage pancreatic failure), fully optimize exercise, nutrition, and sleep, as the speaker hypothesizes this comprehensive approach can cure the disease.

5. Avoid Disuse to Preserve Mitochondria

Actively avoid periods of disuse, such as prolonged bed rest, as it can lead to rapid elimination of mitochondria and measurable defects in VO2 max within as little as 10 days. Recovery of lost mitochondrial function can take significantly longer, such as six weeks to recover 10 days of loss.

6. Medical School for Physiology Research

If interested in research, particularly in understanding how entire living systems operate, consider attending medical school as it offers an intense and well-curated curriculum for learning human physiology. An internship or residency can further deepen understanding of human systems at their extremes.

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