A carbose, a drug that prevents glucose absorption, was found to have a survival benefit. It acts as a caloric restriction mimetic by limiting carbohydrate absorption. Mice lived longer on a carbose, but without weight loss. Lower glucose and insulin levels may explain the extended lifespan. There are speculations about dementia being related to high blood glucose. Regular exercise is important for glucose regulation, but glucose disposal agents like Metformin and SGLT2 inhibitors can also be beneficial. Caloric restriction may not be tolerable or necessary for humans. Energy balance and managing glucose are key factors, with nutrition playing a role in glucose homeostasis.
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Andrew Huberman, Professor of Neurobiology at Stanford University and host of the Huberman Lab podcast joins us in a special journal club episode. Peter and Andrew each present a recent paper that sparked their interests, delving into the findings, dissecting their significance, discussing potential confounders and limitations, and exploring remaining questions. Importantly, they share their methodologies for comprehending research studies, providing valuable insights for listeners to navigate this process independently. Peter presents an epidemiological study reevaluating a noteworthy metformin result that intrigued the anti-aging community, leading to discussions on metformin's geroprotective potential (or lack thereof) and the current lack of aging biomarkers. Andrew introduces a paper examining how our beliefs about the medications we take influence their biological effects, distinguishing the "belief effect" from a placebo effect and highlighting its exciting implications for the future.
We discuss:
- The motivation behind this journal club conversation [2:45];
- Why Peter chose a paper on metformin, how metformin works, and why it generated excitement as a longevity-enhancing agent [9:00];
- Defining insulin resistance and its underlying causes [16:15];
- Metformin as a first-line treatment for type 2 diabetes, and Peter’s evolving interest in metformin as a geroprotective drug [22:00];
- Defining the term “geroprotection” [24:45];
- The 2014 study that got the anti-aging community interested in metformin [26:00];
- Peter presents the 2022 paper that repeats the analytical approach from the 2014 Bannister study [33:15];
- Greater mortality in the metformin group: how results differed between the 2022 paper and the 2014 paper [40:00];
- Understanding statistical significance, statistical power, sample size, and why epidemiology uses enormous cohorts [51:45];
- Interpreting the hazard ratios from the 2022 metformin study, and the notable takeaways from the study [56:45];
- Drugs that may extend lifespan, why Peter stopped taking metformin, and a discussion of caloric restriction [1:08:45];
- Current thoughts on the use of metformin for longevity [1:21:00];
- Could there be any longevity benefit to short periods of caloric restriction? [1:22:45];
- Peter and Andrew’s process for reading scientific papers [1:26:45];
- The biological effects of belief, and how “belief effects” differ from placebo effects [1:32:30];
- The neurobiology of nicotine: a precursor conversation before delving into the paper Andrew chose [1:39:45];
- Andrew presents a paper that demonstrates the impact of belief [1:45:30];
- Analyzing the fascinating results of the Perl paper [1:54:30];
- Exciting implications of the findings about “belief” reported by Perl and colleagues [2:03:15]; and
- More.
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