My Review of Peter Attia’s AMA: What I Agree & Disagree With
In this episode, Matt shares his thoughts on Peter Attia's AMA , exploring areas of agreement and differing perspectives on health and longevity. Topics include the significance of grip strength, biomarkers for health assessment, exercise strategies while traveling, and advancements in longevity research like Klotho and GLP-1 agonists. Matt also discusses the role of AI in healthcare and addresses concerns about direct-to-consumer biological age tests. The episode concludes with a discussion of foundational exercises and the interconnected nature of aging and health.
Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!
ChatGPT With GPT-4 Outperforms Emergency Department Physicians in Diagnostic
Accuracy: Retrospective Analysis - PMC
One of the advancements that both Matt and Peter are most excited about within the geroscience field is the evolution and increasing relevance of artificial intelligence (AI) and machine learning, not just in research but also clinical care. The successful implementation of generative AI in the clinical space opens the opportunity for making clinical care more accessible and caring for underserved populations. This study demonstrates the promise of generative AI in the clinical space by retrospectively analyzing 100 adult patients admitted to the internal medicine emergency department and comparing how the ChatGPT-4 models’ diagnostic output compared to initial diagnosis made by resident physicians and evaluated both against final hospital discharge diagnosis. A point-based system was utilized to grade diagnostic accuracy, with 2 points for accurate, 1 point for partially correct, and 0 for incorrect diagnoses. Across various disease subgroups—cardiovascular, endocrine, gastrointestinal, and infectious diseases—GPT-4 consistently outperformed resident physicians, with statistical significance noted in several comparisons. This underscores the potential of AI to enhance clinical decision-making and potentially streamline clinical care in the future.
Hand grip strength as a proposed new vital sign of health: a narrative review of evidences - PMC
Matt discusses his thoughts on hand grip strength (HGS) as a robust functional marker of biological aging and emphasizes the difference between its correlation with longevity from any causative role it may play. This study conducted a narrative review to evaluate HGS as a potential “vital sign” for systemic health and age-related decline. A correlation was identified between low HGS and several diseases, including Type 2 diabetes, cardiovascular disease, stroke, chronic kidney and liver disease, certain cancers, sarcopenia, and fragility fractures. Additionally, low HGS was associated with increased hospitalization, poorer nutritional status, higher overall mortality, and reduced quality of life. One of the major limitations of HGS is that while it may be a marker of declining health and accelerate biological age, it does not inform interventional care decisions. It is unlikely that improving HGS alone is enough to mitigate the risks of adverse age-related outcomes it is strongly associated with. On the other hand, it may be a strong indicator for an individual that investing in improving functional fitness (e.g. through exercise) could significantly improve healthspan.
Matt and Peter both converge on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as one of the interventions they are most enthusiastic about in regards to improving healthy longevity. This narrative review examines the potential of GLP-1RAs to enhance healthy lifespan by addressing several age-related diseases. The review evaluates findings from clinical trials and studies to evaluate the therapeutic benefits and future applications of GLP-1 RAs. The review highlights that beyond significant benefits in managing type 2 diabetes and obesity, GLP-1 RAs have been associated with cardiovascular risk reduction and possess anti-inflammatory properties. Ongoing clinical developments suggest potential therapeutic roles for GLP-1 RAs in treating chronic kidney disease, metabolic liver diseases, and Alzheimer's disease.Their pleiotropic effects, including metabolic regulation and anti-inflammatory actions, position them as promising candidates for address multi-organ function and mitigating multi-morbidity. The review underscores the need for further research to fully elucidate the potential of GLP-1 RAs in promoting healthy aging in normative aging individuals without unmanaged disease or frailty.
https://www.nature.com/articles/s43587-023-00441-x
The peptide alpha-klothos (klotho) has been in the spotlight as a potential longevity intervention for years due to promising findings of improved lifespan in C. elegans, mice, and humans (within genetic association studies). In this study, researchers investigated the effects of klotho on cognitive function in aged nonhuman primates.The study found that a single administration of low-dose klotho enhanced memory and learning in aged nonhuman primates (sustained at least 2 weeks after administration), while the high-dose did not produce the same effect. This suggests a dose-dependent response, with low-dose klotho improving cognitive function in these primates. This positions klotho as a promising therapeutic agent for mitigating cognitive decline associated with aging in humans.
https://www.nature.com/articles/s41586-024-07701-9
In this study, researchers investigated the role of interleukin-11 (IL-11), a pro-inflammatory cytokine, in aging and age-related diseases using mouse models. They showed that both pharmacological inhibition (with an anti-IL-11 antibody) and mice genetically engineered to lack the IL-11 gene demonstrated improved lifespan (greater than 20% in males and females) and several healthspan metrics including reduced frailty, improved physical function, and a lower incidence of fibrosis and cancer compared to control mice. Mechanistic studies suggest that IL-11 may exert its effects through inhibition of mTOR, similar to rapamycin, prompting Matt to hypothesize that, while effective, this intervention may not show substantially improved longevity benefits compared to rapamycin. Further research is needed to elucidate other benefits of IL-11 on various healthspan metrics (e.g. cognition) as well as mTOR independent mechanisms through which it may be enhancing longevity.
