Episode 102: Adam Konopka talks about metformin’s effects on healthspan and lifespan
// Jan 28, 2020
Our guest today is Dr. Adam Konopka, an assistant professor in the Department of Kinesiology and Community Health at the University of Illinois Urbana Champaign, who believes that aging is the greatest risk factor for just about every single chronic disease that exists.
Adam’s lab, called the Musculoskeletal Aging and Metabolism Lab, is focused on aging-related research.
In addition to doing research that looks at different ways to delay the onset of age-related diseases and functional decline, Adam also has done a lot of research related to the interaction of exercise with metformin. Adam and his colleagues had a paper in Aging Cell that suggested metformin may blunt the health benefits of exercise in healthy older adults, a study that attracted a lot of attention and was highlighted in a story in The New York Times back in June.
Show notes:[00:03:59] Dawn opens the interview mentioning that Adam’s lab is at the University of Illinois, and asks if he decided on Illinois because he grew up in a suburb outside of Chicago. [00:04:28] Dawn asks Adam how he ended up getting into competitive swimming. [00:05:13] Adam explains how his involvement in swimming increased his curiosity about physiology and ways to improve performance, a line of thought that contributed to his eventual majoring in exercise science. [00:05:49] Dawn asks Adam why he decided to minor in entrepreneurship. [00:06:18] Dawn asks Adam about the time when a professor doing research in pediatrics gave Adam the opportunity to volunteer for a study. [00:07:01] Ken mentions that while Adam was a student, he had the opportunity to work on a study which looked at an exercise program used by crew members aboard the International Space Station. Adam explains what his role in this study was. [00:08:05] Adam talks about his time spent at the Mayo Clinic as a postdoctoral research fellow, where he focused his time on looking at skeletal muscle mitochondrial function. [00:09:00] Dawn explains Adam’s notion that mitochondria contribute to obesity induced insulin resistance, a highly debated topic. Dawn goes on to mention Adam’s 2015 paper that looked at obese women who had defects in mitochondrial efficiency and hydrogen peroxide emissions. Adam explains how exercise effectively restored the mitochondrial physiology of these women to that of a leaner phenotype. [00:10:36] Adam discusses a metformin study he was a part of while at the Mayo Clinic, where he tested a hypothesis that had been previously shown in cell culture, to learn if those findings were translatable to humans. [00:11:51] Adam talks about the significance of his findings that metformin improved fasting and postprandial glycemia without inhibiting glucagon-stimulated glucose production. [00:12:59] Ken asks about the two and a half years Adam spent at Colorado State and the research that he conducted there. [00:13:32] Adam explains the mission of, and the research being done at, his lab, The Musculoskeletal Aging and Metabolism Lab, at the University of Illinois. [00:16:25] Ken asks Adam if he has looked into rapamycin and muscle, with respect to mTOR inhibition. [00:17:01] Dawn mentions that Adam took these earlier studies, as well as the research he did as a postdoc, and started asking questions related to the interaction of exercise with metformin. [00:17:30] Ken mentions how this research led to Adam’s paper earlier this year, which was highlighted in the New York Times, and which cast doubt on the idea that exercise and metformin, both of which have been looked at in the context of healthspan extension, work well together in conjunction. [00:19:24] Dawn asks if the negative effects of metformin documented in various studies are relatively modest and or negligible. [00:20:30] Ken asks Adam to speculate on some of his findings, particularly why a certain portion of individuals dosed with metformin are likely to be negative-responders, but at the same time others are positive-responders. Adam talks on this wide variability in the response to metformin. [00:23:12] Dawn asks about Adam’s follow-up research into exercise and metformin that he received a grant for. [00:25:20] Ken mentions it has been suggested that people space out the taking of metformin from the time a person exercises, given that the half-life of metformin is six hours. [00:27:03] Dawn asks if the widely reported health benefits of metformin are worth it possibly inhibiting beneficial mitochondrial adaptations to exercise in older adults. [00:28:38] Dawn asks for Adam to speculate on the mechanisms behind how metformin blunts the adaptive response to exercise. [00:30:48] Ken talks in regards to the NIH-funded trial into metformin called, “Targeting Aging with Metformin” or TAME. Ken asks about Adam’s paper in GeroScience titled, “Taming Expectations of Metformin as a Treatment to Extend Healthspan.” [00:32:57] Ken mentions that he would have liked to have seen rapamycin used instead of metformin in the TAME trial. [00:33:42] Dawn asks if Adam believes that a metformin trial in healthy individuals is currently warranted. [00:34:38] Dawn mentions that while metformin undoubtedly helps individuals suffering from metabolic disease, it is unclear if it has any significant positive effects on already healthy individuals. She goes on to mention that this is paradoxical in light of the fact that the majority of popular interest in off-label use of metformin is in healthy individuals or the so called “worried well,” people who already follow habits of good health. [00:36:16] Ken asks Adam how, in a perfect world, he would design a trial for healthspan-extending intervention in regards to what intervention would he pick, and how he would gauge efficacy considering that an intervention in healthy individuals would ideally need to be continued for several decades in order to determine a true effect. Ken goes on to ask what the pros and cons are of proxies for age in such a study including telomere length as well as biological and epigenetic clocks. [00:39:26] Ken asks how Adam would adjust for lifestyle behaviors like dietary manipulation and exercise that activate similar pathways to drugs like metformin and rapamycin in his hypothetical study. [00:40:44] Dawn asks if Adam has much expectation in extending lifespan with pharmacological methods, or if he thinks that merely healthspan will increase while we see a so-called compression of morbidity, and if he thinks that these pharmacological treatments are likely to surpass lifestyle interventions like exercise. [00:42:39] Ken asks if Adam has looked at PPAR-D agonists, which are a class of drugs that provide some of the effects of exercise pharmacologically. [00:43:50] Adam gives his advice to people interested in extending their healthspan. [00:44:57] Dawn asks what Adam’s diet and exercise routine look like. [00:46:11] Dawn mentions that she knows that Adam and his wife have a young child and closes the interview asking Adam what he does for fun in his spare time.
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