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:

• The Broad Institute of MIT and Harvard [8:00];
  
• Vamsi's academic background [10:30];
  
• Advice for college students and med students considering a career in medicine and/or medical research [15:30];
  
• Vamsi's focus on mitochondria and mitochondrial disorders [20:00];
  
• The mitochondrial genome: Lineage, endosymbiosis, and reductive evolution [23:15];
  
• How many diseases can be attributed to mitochondrial mutations? [28:45];
  
• Nuclear DNA and mtDNA: Roles, interaction, communication, and biogenesis [31:30];
  
• Which cells have the most mitochondrial DNA? And how often does mitochondria turn-over in a cell? [37:30];
  
• Does ALL of your mitochondrial DNA come from your mother? [40:00];
  
• Mitochondria 101: The powerhouse of the cell, electron transport chain, and the NADH/NAD ratio [44:00];
  
• 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];
  
• Mitochondrial diseases Vamsi studies in his lab [55:15];
  
• Mitochondria and oxygen: Poor oxygen utilization and excess oxygen contributes to the pathology seen in some of the rare mitogenic diseases [1:02:00];
  
• What VO2 max can tell us about mitochondrial function, insulin resistance, type 2 diabetes, and more [1:10:00];
  
• Can studying mitochondrial disease provide insights into the common forms of aging?  [1:18:45];
  
• Could muscle cell inflammation (a signature of aging) be caused by mtDNA damage being confused as foreign bacteria? [1:22:00];
  
• Exercise and mitochondrial health: Is there an optimal exercise strategy to slow the aging process? [1:27:00];
  
• What autophagy means in the context of mitochondria [1:36:15];
  
• Metformin's impact on exercise and lactate levels [1:40:15];
  
• How might metformin confer longevity benefits? [1:48:15];
  
• Hypoxia as a potential therapeutic option for mitochondrial disease [1:52:45];
  
• Cancer prevention and treatment: hyperbaric oxygen chambers, targeting single carbon metabolism of the mitochondria, and more [2:00:00];
  
• Chronic diseases have altered mitochondria: Evidence for mitochondrial dysfunction causing Parkinson's disease  [2:04:30];
  
• Why Vamsi is very optimistic about the possibility of targeting mitochondrial proteins as therapies [2:09:30];
  
• Is it theoretically possible to genetically engineer a better functioning mitochondria? [2:14:30];
  
• Vamsi's fantasy experiment in an unconstrained world [2:20:15]; and
  
• More.

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