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    • Exploring the Genetics of Aging and the Benefits of Metformin in Relation to LongevityNir Barzilai, a leading expert in aging biology, discusses the potential benefits of metformin and its effects on lifespan and health, providing valuable insights for those interested in longevity.

      Nir Barzilai is a leading expert in the field of longevity and the genetics of aging. He has extensive knowledge about the clinical benefits of metformin, a drug being tested in a clinical trial for non-diabetics in relation to aging. Barzilai also provides insights on insulin resistance, IGF, growth hormone, and their potential effects on lifespan and health. The discussion covers various topics including autophagy, caloric restriction, and NAD. While the episode delves into technical details, it remains accessible to a wider audience. Overall, Barzilai's expertise in the field of aging biology offers valuable insights and clarifications, making the conversation insightful for anyone interested in longevity.

    • Exploring the Biology of Aging: A Holistic ApproachUnderstanding the aging process requires a comprehensive perspective, not just focusing on hormones, but examining various factors that contribute to aging.

      Aging and the biology of aging have long been subjects of interest and exploration for Nir Barzilai. His curiosity was sparked by observing his aging grandfather and questioning the difference between chronological age and biological age. As a physician, Barzilai recognized the role of endocrinology in the aging process and the potential of hormones to impact aging. However, he also saw that the effects of aging extended beyond just hormone changes, and that there were various factors at play. This broader perspective led him to approach the study of aging from a more holistic viewpoint. It highlights the importance of considering multiple factors and not relying solely on hormone replacement when it comes to addressing the aging process.

    • Age and context impact the effectiveness of estrogen and the challenges of approving new drugs.Hormonal effects and drug approval require considering age, context, extensive research, and evaluation for effective and safe interventions.

      The effectiveness of estrogen varies based on age and context. While estrogen showed positive effects in younger animals when it came to stroke prevention, it had the opposite effect in older animals. This demonstrates the need to consider age and other factors when studying hormones and their impact. Additionally, the discussion highlights the lengthy process and challenges of bringing a drug like metformin to the United States. The FDA required extensive studies and evidence before approving metformin for use in the US, including understanding its mechanism of action. This conversation emphasizes the importance of thorough research and evaluation when introducing new drugs.

    • Understanding the Complexities of Metformin-Associated Lactic AcidosisMetformin's association with lactic acidosis is not solely due to the drug itself, but is influenced by other factors such as kidney failure or heart attacks. The negative side effects of drugs like metformin are often intertwined with pre-existing conditions in patients. Additionally, metformin's benefits for type 2 diabetes extend beyond glucose control, as it also improves muscle insulin sensitivity and glucose disposal.

      Metformin, a widely used drug for type 2 diabetes, has been associated with a condition called metformin-associated lactic acidosis (MALA). However, it is now recognized that MALA may not be solely caused by metformin itself, but rather a combination of factors, including kidney failure or heart attacks. This association has led to a shift in understanding, emphasizing that the negative side effects of drugs like metformin and rapamycin are often difficult to isolate from pre-existing conditions in patients. Furthermore, it is interesting to note that metformin can improve type 2 diabetes not only by controlling glucose levels but also by increasing muscle insulin sensitivity, leading to enhanced glucose disposal.

    • Metformin: A Promising Anti-Aging DrugMetformin, a drug used for diabetes, may have potential benefits for the aging process. Its effects on insulin resistance and lifespan suggest it has broader applications beyond diabetes treatment.

      Metformin, a drug commonly used to treat diabetes, has potential benefits for the aging process as well. Initially, there was a focus on insulin resistance as the root cause of diabetes, but it is now understood to be a collaboration of factors. Metformin primarily affects hepatic glucose production, but it also acts as an insulin sensitizer in muscle tissue. Insulin resistance is a complex concept that involves the inability of certain cells, such as muscle cells, to respond effectively to insulin. The liver's role in insulin resistance is particularly complicated. Furthermore, research on nematodes has shown that decreasing insulin sensitivity can lead to increased lifespan. This suggests that metformin's effects on aging may go beyond its diabetes-related properties.

    • The Link Between Visceral Fat and LifespanRemoving visceral fat in rats led to longer lifespans and improved health, highlighting the importance of reducing visceral fat for longevity and overall well-being.

      Removing visceral fat in rats extended their lifespan and improved their health. The experiment showed that rats who underwent surgery to remove their visceral fat lived significantly longer compared to rats with intact visceral fat. Although the rats with removed visceral fat did not live as long as rats on caloric restriction, they still experienced a 20% increase in lifespan. Additionally, these rats maintained better health and did not experience weight loss in their later years like the rats with intact visceral fat. This suggests that reducing visceral fat can have a positive impact on longevity and overall health.

    • The Protective Role of Insulin Resistance and its Relationship with Aging.Insulin resistance is a stress response that safeguards the body by redistributing excess glucose, but it may contribute to health issues like diabetes and aging-related complications.

      Insulin resistance is a protective mechanism and a stress response in the body. The experiment with the Zucker rats showed that when these obese rats had their visceral fat removed before puberty, they did not develop diabetes. However, when the fat grew back, they became diabetic. Furthermore, the removal of visceral fat in rats that already developed diabetes did not reverse the condition. This led to the realization that insulin resistance is a mechanism to protect the body. The muscle becomes insulin resistant when there is an excess amount of glucose, redirecting it to other organs like the liver and fat. This understanding provides insights into the relationship between insulin resistance and aging.

    • The Impact of Insulin Resistance and Sensitivity on Health and LifespanUnderstanding insulin resistance and sensitivity is crucial for maintaining good health and increasing longevity. Interventions like rapamycin can increase lifespan in rodents but also cause insulin resistance. Exercise and alternative glucose uptake mechanisms play a significant role in managing insulin resistance.

      Insulin resistance and insulin sensitivity have significant impacts on lifespan and health. By studying animals with insulin resistance and sensitivity, researchers have discovered that interventions like rapamycin can cause insulin resistance but also increase lifespan in rodents. Insulin resistance can occur throughout the body, including in muscles, liver, and the brain. Insulin receptor substrates like IRS 1 and IRS 2 play key roles in glucose uptake by the muscles, which can occur both passively and through non-insulin mediated mechanisms. Exercise and AMP kinase may enhance non-insulin mediated glucose uptake. This conversation highlights the importance of understanding insulin resistance and sensitivity in relation to overall health and longevity.

    • Exploring the complexity of metabolic processes and the role of glucose and insulin in different parts of the body.Understanding metabolism is a challenging task, and comprehensive testing is needed to assess insulin sensitivity and glucose uptake in muscles as clinical indicators.

      Metabolic processes are complex and interconnected. The researchers discuss the role of glucose and insulin in various parts of the body, particularly the hypothalamus, liver, and muscles. They highlight the importance of the vagus nerve in connecting the central nervous system to the periphery, like the liver. The concept of insulin resistance is also discussed, with a focus on glucose uptake in the muscle as a clinical indicator. The researchers also emphasize the need for comprehensive testing, such as oral glucose tolerance tests, to understand insulin sensitivity. Overall, the conversation shows that understanding metabolism is challenging, and there is still much to learn in this field.

    • Importance of Measuring Insulin Levels and Understanding Glucose DisposalMeasuring insulin levels helps in understanding glucose disposal, managing diabetes, and preventing other diseases like heart attacks or strokes. Understanding insulin signaling and glucose transport enhances healthcare approaches.

      Measuring insulin levels in patients, especially those with type 2 diabetes, can provide valuable insights into their glucose disposal and overall health. The difference in hyperinsulinemia between individuals may play a significant role in insulin resistance and the development of other diseases like heart attacks or strokes. Understanding the insulin response and its impact on glucose disposal is crucial in managing and preventing these conditions. The liver's role in glucose production and its sensitivity to increasing glucose concentrations highlight its importance in maintaining proper bodily function. By exploring and comprehending the intricacies of insulin signaling and glucose transport, we can gain a deeper understanding of our bodies and enhance our approaches to healthcare.

    • The Potential of Metformin as an Anti-Aging DrugMetformin, a drug commonly used for diabetes, has shown potential for extending life and improving health in individuals without diabetes, making it a possible anti-aging treatment.

      Metformin, a drug commonly used for diabetes, has shown potential for extending life and improving health in individuals without diabetes. Studies in rodents and nematodes have demonstrated that metformin can increase lifespan and improve healthspan by around 50%. The initial hypothesis for using metformin in aging research was not related to glucose metabolism, but rather the potential anti-cancer effects observed in animal models. However, further studies showed that even mild effects on insulin can significantly improve health and increase lifespan. The decision to conduct a study with metformin in humans was motivated by a UK publication that analyzed prescription data and observed a correlation between metformin usage and decreased mortality. This highlights the potential of metformin as an anti-aging drug that can enhance both lifespan and healthspan.

    • The Potential of Metformin in Improving Health and Slowing AgingMetformin, a drug commonly prescribed for type 2 diabetes, has been found to significantly reduce mortality rates and prevent aging-related diseases, highlighting its potential for improving health outcomes and slowing down the aging process.

      Metformin, a commonly prescribed drug for type 2 diabetes, has shown to have a significant effect on reducing mortality and preventing aging-related diseases in humans. A study compared 78,000 individuals on metformin with diabetes to a control group without diabetes and found a 17% lower mortality rate among those on metformin. Despite having more diseases and obesity, the metformin group had a lower mortality rate. However, the study did not validate the optimal dose or the duration of metformin use for achieving these benefits. Additionally, multiple studies have shown an association between metformin use and a reduced risk of various cancers, excluding prostate cancer. These findings highlight the potential of metformin in improving health outcomes and slowing down aging.

    • Exploring the Potential of Metformin in Targeting AgingMetformin, a freely available diabetes drug, shows promising results in preventing various age-related conditions, emphasizing the need for funding and regulatory approval to further study its potential benefits for aging.

      There is a study called Tame (Taming or targeting aging with metformin) that aims to prove the concept that aging can be targeted. One of the challenges of this study is finding funding since aging is not considered a disease by the NIH and there is no way to make money from it for pharmaceutical companies. Metformin, a free drug used to treat diabetes, has shown promising results in preventing cancer, cardiovascular disease, and even improving cognitive function. It is seen as a safer option compared to rapamycin, which has potential side effects. The professors involved in the study are advocating for a new indication for metformin and have even gone to the FDA and Senate with their proposal.

    • Targeting Aging for Disease PreventionAddressing the biology of aging can help prevent various age-related diseases and improve overall health outcomes.

      Targeting the biology of aging can help prevent a range of age-related diseases. The FDA initially questioned the importance of preventing aging, but the discussion highlighted how slowing down the aging process can have significant implications for diseases like cardiovascular disease, cancer, Alzheimer's, and even diabetes. The FDA's focus on short-term costs and complications associated with diabetes was counterintuitive, as the long-term cost burden of diabetes becomes much more elaborate. This conversation emphasized the need to redefine aging in clinical studies and consider the correlation between different diseases and aging. Ultimately, by addressing the underlying biology of aging, we have the potential to prevent a variety of diseases and improve overall health outcomes.

    • Rethinking Aging: A Paradigm Shift in Addressing Aging and DiseaseBy shifting focus from individual diseases to targeting aging itself, there is potential to optimize health span and extend overall lifespan, necessitating collaboration and a broader approach in research. Aging should be seen as a treatable condition.

      The approach to addressing aging and its associated diseases requires a shift in mindset. The traditional focus on individual diseases overlooks the potential benefits of targeting aging itself. By treating aging as a composite outcome and delaying its onset, there is an opportunity to optimize health span and extend overall lifespan. This paradigm shift challenges the siloed thinking of specific disease areas and necessitates a broader approach. It also highlights the importance of collaboration and breaking down barriers between different research fields. While there may be practical challenges such as funding and study design, the conceptual leap in seeing aging as a treatable condition is crucial to advancing the field and developing effective interventions.

    • Challenges faced by the National Institute of Aging in securing funding for important research on aging and disease.Despite budget constraints, the National Institute of Aging is making efforts to secure funding for their study on aging, aiming to improve health outcomes for older individuals.

      The National Institute of Aging is facing budget constraints, which poses a challenge for funding important research on aging and disease. Nir Barzilai and his team are working tirelessly to gather the necessary funds for their study on aging, which amounts to $70,000,000. They have managed to raise half of the required amount through philanthropic sources, but the remaining funding is contingent upon commitments from other institutes like NCI and HLBDK. While these institutes haven't made a concrete commitment yet, there is hope that they will provide the necessary funds. Additionally, alternative non-profit organizations could step in to support the study if the NIH deems it too risky. Despite these challenges, Barzilai anticipates starting the study in early 2019 with 14 centers and 3,000 subjects aged 65 to 80. The study aims to target aging and improve health outcomes for older individuals.

    • Metformin's Potential Anti-Aging Effects ExploredMetformin, a diabetes drug, may have anti-aging properties due to its activation of AMP Kinase and epigenetic changes. Its effects extend beyond the liver and include both AMP and mitochondrial-dependent actions.

      Metformin, a drug commonly used to treat diabetes, has potential anti-aging properties at the cellular level. The drug exerts its effects through the activation of AMP Kinase (AMPK) and also through epigenetic changes, such as histone deacetylation. These mechanisms are believed to contribute to the beneficial effects of metformin on aging. Additionally, metformin enters cells through a transporter called OCT 1, which is not uniformly expressed in all cell types. While there is a higher concentration of OCT 1 in the liver, metformin's effects are not limited to this organ. The study aims to investigate the impact of metformin on aging and longevity, considering both its AMP-dependent and mitochondrial-dependent actions.

    • Potential Anti-Aging Effects of MetforminMetformin, a commonly prescribed drug for type 2 diabetes, may have potential anti-aging effects by activating AMPK and reducing inflammation, but more research is needed to fully understand its role.

      Metformin, a commonly prescribed drug for type 2 diabetes, may have potential anti-aging effects. Metformin works by activating AMPK (adenosine monophosphate-activated protein kinase), which is responsible for nutrient sensing and exercise-mimetic pathways in the body. The drug also has an impact on mitochondria, inhibiting oxidative pathways and reducing ROS (reactive oxygen species) production, resulting in less inflammation. However, the exact mechanism and optimal dosage for aging benefits are still not fully understood. Additionally, metformin can lower insulin levels and decrease inflammatory factors. This multi-faceted approach illustrates the complexity of biology and highlights the need for comprehensive research to fully understand the role of metformin in aging.

    • Metformin: A Valuable Tool in Fighting Aging, but Only the BeginningMetformin, though not perfect, is a useful starting point in targeting aging. With ongoing research, better drugs and therapies can be developed to extend human lifespan beyond the current limits.

      Metformin, despite not being a perfect drug, is a valuable tool in the fight against aging. It may not excel in any particular aspect, but it does multiple things reasonably well, making it a useful starting point to demonstrate the possibility of targeting aging. Its extensive safety and efficacy data, gathered from billions of patient years, further emphasize its value. However, it's important to recognize that Metformin is just the beginning. There is potential for much better drugs and combination therapies in the future. With approximately 35 years of life beyond the age of 80, there is still low-hanging fruit to be explored in extending human lifespan. While the future holds promise, paving the road starts with utilizing the tools available to us, such as Metformin.

    • The Longevity Dividend: Delaying Chronic Diseases for a Healthier LifeDelaying the onset of chronic diseases through healthier living can extend functional life, improve quality of life, and reduce healthcare costs.

      Centenarians, despite their longer lifespan, still experience chronic diseases such as heart disease, cancer, and Alzheimer's. However, their genetic gift allows them to delay the onset of these conditions, giving them a 20 to 30-year bonus of functional life. This phenomenon is known as a phase shift in when they develop chronic diseases. Moreover, research suggests that centenarians experience a compression of morbidity, meaning they have a shorter period of ill health before passing away. This information supports the concept of the longevity dividend, which explores the potential benefits of healthier aging. By living healthier and delaying chronic illnesses, individuals can not only improve the quality of their lives but also reduce healthcare costs significantly.

    • The Role of the IGF Axis in Centenarians and LongevityThe levels of IGF-1 in centenarians may not always accurately reflect their health or aging status, indicating the complexity of genetic factors influencing longevity. Further research is needed.

      The growth hormone IGF axis plays a crucial role in the genetic differences observed in centenarians and their offspring. Approximately 60% of centenarians have genomic alterations related to this system. The aging process is associated with a decline in both growth hormone and IGF-1 levels. However, it is important to note that measuring IGF-1 levels alone may not always accurately reflect an individual's health or aging status. Association studies have revealed that among centenarians, those with the lowest IGF-1 levels tend to live longer, particularly among women. These findings shed light on the complexity of genetic factors influencing longevity and suggest that further research is needed to fully understand the relationship between the growth hormone IGF axis and aging.

    • Sex differences and genetic mutations play a crucial role in understanding the effects of IGF and GH on aging and cognitive health.Low IGF levels in women may be associated with better cognitive health, highlighting the importance of considering sex differences and genetic mutations in understanding the role of IGF in aging.

      The levels of IGF (insulin-like growth factor) and GH (growth hormone) differ between men and women, and these differences have significant implications for aging and cognitive health. The researchers discovered that studying only males in their labs was a mistake, as they missed crucial insights into the sex-specific effects of these hormones. They found that low IGF levels in women were associated with fewer cognitive problems compared to those with higher levels. Additionally, they identified clusters of functional mutations in the IGF receptor, demonstrating that these specific mutations are more relevant to human aging than generalized genomic findings. This highlights the importance of considering sex differences and genetic mutations in understanding the role of IGF in aging.

    • The Impact of Genetic Mutation on Health OutcomesA specific genetic mutation resulting in low levels of IGF may offer health benefits, including a lower incidence of age-related diseases and a taller stature, challenging previous assumptions about genetics and health.

      Individuals with a specific genetic mutation in the growth hormone receptor, resulting in low levels of IGF (insulin-like growth factor), may experience certain health benefits. Despite having high levels of growth hormone, which is not effectively expressed through the liver into IGF, these individuals have lower IGF levels. Interestingly, research has shown that these individuals have a lower incidence of age-related diseases such as cancer and diabetes. Additionally, it was found that they have a taller stature, contrary to what one would expect. Further studies are needed to replicate these findings in other populations. This highlights the complexity of genetics and their impact on health outcomes, challenging previously held assumptions.

    • Genetic and epigenetic factors influencing longevityGenetic mutations, overexpression of microRNA clusters, and mutations in specific genes contribute to cellular processes and regulation, affecting aging and longevity. Understanding these factors can aid in studying and promoting healthy aging.

      There are genetic mutations and epigenetic factors that play a significant role in longevity. Through various studies and replication of data, it has been found that individuals who live the longest have specific mutations in the growth hormone receptor. These mutations affect the activation and proliferation of lymphocytes, leading to changes in cellular processes. Additionally, the overexpression of certain microRNA clusters and mutations in the FOXO3A gene have been observed in centenarians. These genetic and epigenetic factors contribute to the regulation of cellular homeostasis and play crucial roles in aging and longevity. Understanding these pathways and genetic variations can help further research on longevity and potentially lead to interventions for promoting healthy aging.

    • The complexity of genetic analysis and the importance of a holistic approachGenetic variations are just one piece of the puzzle, and many diseases are influenced by both genetic and environmental factors. The overemphasis on genetics can lead to misconceptions and frustration. Lifestyle choices and longevity genes also play a significant role in determining health.

      Genetic analysis is complex and often misunderstood. While certain genetic variations may be significant, it is important to recognize that they are just one piece of the puzzle. Many diseases and conditions are multifactorial, meaning they are influenced by a combination of genetic and environmental factors. Simply having a complete sequence of one's genes does not equate to having a deterministic relationship with a disease. The overemphasis on genetic analysis can lead to frustration and misconceptions. Additionally, the study of centenarians reveals that even individuals with numerous genetic mutations can live long, healthy lives, suggesting that other factors such as longevity genes and lifestyle choices play a significant role. Overall, understanding genetics requires a holistic and nuanced approach.

    • The role of genetics in longevity and the mystery of LP little a (LPA)The CTP VV gene is associated with better health outcomes in centenarians, but the persistence of LP little a (LPA) after age 80 raises questions about its role in longevity.

      There is a protective gene called CTP VV that is found in centenarians. This gene is associated with higher levels of HDL, larger lipoprotein particle size, and lower CTP levels. People with the CTP VV phenotype have a lower risk of age-related diseases, including cognitive decline. However, what is still unclear is why the concentration of LP little a (LPA) doesn't flatline after the age of 80, despite the protective effects of the CTP VV gene. Further research is needed to understand the role of LPA in longevity and its interaction with other genes. Overall, this conversation highlights the importance of genetic factors in determining longevity and the need for further exploration in this field.

    • Exploring the complexities of Lp(a) and heart diseaseFurther research is needed to understand why some individuals with high levels of Lp(a) do not develop heart disease, and to improve testing methods for accurate risk assessment and treatment decisions.

      There is a need for further research and understanding when it comes to certain health conditions. Specifically, the discussion revolves around Lp(a) and its association with heart disease. It is observed that some individuals with high levels of Lp(a) do not develop premature heart disease, while others do. This leads to the question of whether there are different phenotypes of Lp(a) that have varying levels of virulence. Additionally, the conversation highlights the limitations in current testing methods, such as the lack of an HDL functional assay, which hinders accurate risk stratification and treatment decisions. Further investigations involving gene to gene interactions, phenotyping, and proteomics are necessary to better comprehend these complexities and improve patient care.

    • Amgen's cancer drug repurposed for increasing lifespan in aging individuals shows promising results in mice studyAmgen's modified drug has potential for increasing lifespan and improving health in aging individuals, but more research is needed to confirm its effectiveness and ensure safety.

      A drug developed by Amgen, initially intended for cancer treatment, has shown potential for increasing health span and lifespan in aging individuals. Although the drug failed in treating pancreatic cancer, it was modified to target IGF receptors in the brain for research on aging. The study conducted on female mice demonstrated a 10% increase in lifespan and improved overall health. There was a decrease in inflammatory markers and cardiovascular protection. However, there is still a need to determine the drug's effectiveness on male mice. This drug could be a potential treatment option for age-related issues in the future, but further research is required before it can be commercialized.

    • Gender Differences in Inflammatory Response to Growth Hormone TreatmentWhile growth hormone treatment shows benefits for females, its effects on males are inconclusive. More research is needed to understand the relationship between inflammation, IGF levels, and sex hormones, and to explore alternative treatment options.

      There is a difference in the inflammatory response to growth hormone treatment between males and females. While preclinical studies have shown that the treatment is beneficial for females, the same cannot be said for males. There is evidence suggesting that higher levels of IGF in men may lead to better functionality, but it is not statistically significant. Therefore, it is hard to conclude that giving growth hormone is bad for men. The inflammation caused by low IGF levels is still not fully understood, especially in relation to sex hormones. Further studies are needed, including experimenting with younger mice to explore the protective effects of sex hormones and investigating alternative treatments like microRNA. Ultimately, fasting remains the most obvious way to manipulate IGF levels.

    • Exploring the potential benefits of a cyclic approach to IGF levels and autophagy through fasting and intermittent fasting.Adopting a cyclic approach to IGF levels through fasting and intermittent fasting may have significant impacts on health and longevity, potentially improving overall well-being through enhanced autophagy.

      There is a potential benefit to adopting a cyclic approach to IGF levels and autophagy. Peter Attia discusses how fasting has a significant impact on his IGF levels, causing them to decrease during the fast and slowly rise afterwards. He wonders if this cyclic approach to IGF is healthier compared to consistently being calorically restricted. Nir Barzilai highlights the importance of IGF decrease for longevity but also mentions that intermittent fasting, rather than caloric restriction, may be more effective in achieving low IGF levels. Both researchers emphasize the need to study the timeline and effects of autophagy in humans. Overall, understanding the relationship between fasting, IGF levels, and autophagy could potentially lead to new insights on improving health and longevity.

    • Time Restricted Feeding and Metformin: Uncertain Impact on Human Health and AgingMore research is needed to determine the full effects of time restricted feeding and metformin on human health and aging.

      Time restricted feeding may not have the same level of impact in humans as it does in mice. While mice can go 16 hours without eating, which is akin to a human not eating for 3 days, it is uncertain if humans experience the same level of deprivation. However, there doesn't seem to be a downside to time restricted feeding for humans either. The conversation also highlights the use of metformin, a drug commonly used for diabetes, and its potential effects on aging and weight loss. Preliminary studies suggest positive effects of metformin in humans, but more research is needed to fully understand its benefits. Overall, there is still much to learn about the effects of time restricted feeding and metformin on human health and aging.

    • The Potential Effects of Metformin on Weight and AgingMetformin, a medication for type 2 diabetes, can potentially lead to weight loss and anti-aging effects through changes in metabolism and gene expression, but further research is required for a complete understanding.

      Metformin, a commonly prescribed medication for managing type 2 diabetes, may have additional effects on weight and aging. While weight loss is not the primary purpose of metformin, some patients have reported significant weight loss after taking the medication. This weight loss seems to be associated with changes in metabolism and gene expression, particularly in relation to fatty acid and pyruvate metabolism. Furthermore, the conversation suggests that metformin may have anti-aging effects, as it appears to influence genes associated with DNA repair and aging. However, more research is needed to understand the full extent of metformin's effects on weight and aging.

    • Importance of Clinical Studies and Objective Data in Evaluating Interventions and TreatmentsClinical studies help validate claims about therapies and products, while objective data collection through tools like Fitbit aids in personal health monitoring, but caution is needed in interpreting personal experiences without clinical evidence.

      Conducting clinical studies is crucial for truly understanding the effectiveness of certain interventions or treatments. The discussion highlights the limitations of relying solely on anecdotal evidence or assumptions. It is emphasized that clinical studies provide the necessary evidence to support or debunk claims about therapies or products. The conversation also touches upon the complexity of different substances, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMM), and the uncertainty about their stability and effectiveness. The importance of objective data collection through tools like Fitbit for personal health monitoring is mentioned, but it is acknowledged that personal experiences should be cautiously interpreted without robust clinical evidence.

    • The Unresolved Effects of NAD on the Body and Potential Areas for DevelopmentComprehensive clinical research is necessary to fully understand the impact of NAD on humans and to explore alternative methods of delivery for more efficient cellular absorption.

      The effects of NAD on the body, particularly regarding sleep patterns and cellular absorption, are still not well understood. While there is some promising evidence in animal studies, it is difficult to determine the exact impact on humans without comprehensive clinical research. Additionally, the popular method of intravenous administration of NAD may not be as effective as previously thought. A potential development in the field is the creation of a drug precursor that can be taken orally or intravenously outside of the liver, which could provide more efficient delivery to cells. Ultimately, more research is needed to fully support the use and benefits of NAD.

    • Potential Benefits of Metformin in Non-Diabetic Individuals: An Ongoing ResearchThis ongoing research explores the potential benefits of metformin in non-diabetic individuals, but it is crucial to await completion and clinical evidence before drawing any conclusions. Further investigation is needed.

      There is ongoing research on the potential benefits of metformin in non-diabetic individuals. However, it is important to understand that this study has not been completed yet, and there is no clinical evidence to prove its safety and effectiveness in this context. Additionally, it is crucial to be cautious about potential biases in the study's recruitment process, as individuals who volunteered for the study may already be engaging in other healthy behaviors, like exercise. Furthermore, it is essential to recognize that while there is hope and promise for the prevention of age-related diseases through advancements in aging research, there are still blind spots that need to be identified and addressed. Overall, the conversation emphasizes the importance of evidence-based research and the need for further investigation in this field.

    • Aging, Pillars, and Treatment PerspectivesEngaging dialogue and shared optimism between Peter Attia and Nir Barzilai highlight the interconnected nature of aging pillars and the potential for effective age-related treatments.

      Peter Attia and Nir Barzilai share common philosophies and points of view regarding aging. They discuss the interconnected nature of the pillars of aging, such as autophagy and metabolism, and how improving one pillar can positively impact others. While their data primarily comes from animal studies, they believe that aging is universal and that treatments like rapamycin can delay aging in various animals. They also acknowledge the potential differences between genders, but based on previous data on metformin, they assume no significant gender effects. Despite Peter feeling unwell, he eagerly pursued the discussion, emphasizing the importance of their conversation. They even plan to have dinner together and organize a seminar on not just caloric restriction. Their engagement in meaningful dialogue and their shared optimism for finding effective age-related treatments is the main takeaway.

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    • The role of the autonomic nervous system (ANS) in regulating HRV [25:45];
    • The decline in HRV with age, and the mitigating effects of fitness and other lifestyle factors [33:30];
    • The role of genetics in HRV, the modifiability of HRV, and a comparison of VO2 max and HRV as predictors of mortality [37:00];
    • How aging affects HRV and sympathetic drive, and the importance of spontaneous movement and exercise in maintaining the body's adaptability [43:30];
    • How Morpheus measures HRV using RMSSD and normalizes it to a 100-point scale for easier interpretation [49:45];
    • The Morpheus system: development, integration with various metrics, and personalized daily training recommendations to optimize fitness and recovery [51:30];
    • The benefits of morning HRV readings for assessing daily readiness compared to overnight HRV measurements [1:03:00];
    • Why Morpheus recommends using a chest strap rather than an arm band [1:10:00];
    • The impact of consistent exercise, stress, alcohol, and other lifestyle factors on HRV [1:11:15];
    • Optimizing zone 2 training with Morpheus [1:18:15];
    • Using heart rate recovery (HRR) as an indicator of athletic conditioning and the balance between aerobic and anaerobic systems [1:22:45];
    • The importance of tracking HRV trends over time rather than focusing on data from a given day [1:29:00];
    • Effect of GLP-1 agonists on heart rate and HRV [1:34:45];
    • Where HRV belongs in the hierarchy of health metrics [1:42:00];
    • Parting thoughts [1:46:30]; and
    • More.

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    The Peter Attia Drive
    enJune 10, 2024

    #304 – NEW: Introducing quarterly podcast summaries - Peter shares his biggest takeaways on muscle protein synthesis, VO2 max, toe strength, gut health, and more

    #304 – NEW: Introducing quarterly podcast summaries - Peter shares his biggest takeaways on muscle protein synthesis, VO2 max, toe strength, gut health, and more

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    In this quarterly podcast summary (QPS) episode, Peter introduces a new format aimed at summarizing his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from each episode, covering diverse topics such as protein and muscle building with Luc van Loon, toe strength with Courtney Conley, VO2 max with Olav Aleksander Bu, liquid biopsies for cancer with Alex Aravanis, gut health and probiotics with Colleen Cutcliffe, and road safety with Mark Rosekind. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions.

    If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #304 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • How Peter keeps track of his takeaways from each podcast episode [5:15];
    • Luc van Loon episode: fat utilization, muscle protein synthesis, dietary protein, aging and inactivity, and more [8:45];
    • Behavioral changes that have come about from the conversation with Luc van Loon [23:45];
    • Courtney Conley episode: importance of toe strength and the impact of dedicated foot training [26:45];
    • Olav Aleksander Bu episode: the importance of VO2 max for lifespan, and the practicalities of measuring and improving VO2 max [36:45];
    • Behavioral changes that have come about from the conversation with Olav [56:00];
    • Alex Aravanis episode: liquid biopsies for cancer detection [1:01:30];
    • Colleen Cutcliffe episode: the importance of gut bacteria balance, and the potential therapeutic uses of probiotics, particularly Akkermansia [1:16:45];
    • Mark Rosekind: the significant issue of road fatalities and injuries, their causes, and practical safety measures to reduce risks [1:27:00]; and
    • More.

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    The Peter Attia Drive
    enJune 03, 2024

    #303 - A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer's disease | Dena Dubal, M.D., Ph.D.

    #303 - A breakthrough in Alzheimer’s disease: the promising potential of klotho for brain health, cognitive decline, and as a therapeutic tool for Alzheimer's disease | Dena Dubal, M.D., Ph.D.

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    Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.

    Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease.

    We discuss:

    • Dena’s fascination with aging and how she came to study klotho [3:30];
    • Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45];
    • Potential benefits of klotho on brain health [22:00];
    • The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45];
    • The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement [46:45];
    • Benefits of klotho observed in a mouse model of Parkinson’s disease [55:45];
    • Benefits of klotho observed in a mouse model of Alzheimer’s disease [1:03:00];
    • Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00];
    • Speculating why a single klotho injection has such long-lasting effects [1:25:30];
    • Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45];
    • The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease [1:34:45];
    • The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15];
    • Measuring klotho levels and determining an individual’s KL-VS status [1:52:15];
    • The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research [1:58:00]; and
    • More.

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    The Peter Attia Drive
    enMay 27, 2024

    #302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.

    #302 - Confronting a metabolic epidemic: understanding liver health and how to prevent, diagnose, and manage liver disease | Julia Wattacheril, M.D., M.P.H.

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    Julia Wattacheril is a physician scientist and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) program at Columbia University Irving Medical Center. In this episode, Julia delves deep into the complex world of liver health, beginning with a foundational overview of liver physiology. She provides an in-depth look at how alcohol impacts liver function, breaking down the metabolism of ethanol and its detrimental effects. Julia then shifts the focus to understanding liver function tests and optimal enzyme levels, providing a detailed explanation of AST and ALT and elucidating why fluctuations in these levels may or may not be concerning. She provides a primer on the four major stages of liver disease, discussing risk and emphasizing the importance of early diagnosis. Julia highlights the role of liver disease in increasing the risk of cancer and cardiovascular disease and covers in detail the various strategies for diagnosing, treating, and preventing the progression of liver disease.

    We discuss:

    • Julia’s training, the importance of liver health, and the challenges and innovations of hepatology [3:15];
    • The complex and crucial functionality of the liver, its four most essential functions, and more [8:45];
    • Liver injuries: historical and evolving understanding of causal factors, and the progression to liver diseases and cancer [13:15];
    • How the liver metabolizes nutrients and what happens in the presence of excess calories or alcohol [24:45];
    • Methods of diagnosing liver disease and how insights guide treatment and management strategies [33:30];
    • The poisonous nature of ethanol to the liver [40:30];
    • Varied responses to alcohol, damaging effects of alcohol beyond the liver, and the process of advising patients on their alcohol consumption [47:15];
    • Understanding liver enzymes AST and ALT—interpreting levels, lifestyle factors that affect them, and diagnostic approaches [58:30];
    • Interpreting liver function tests for fatty liver disease, and the challenges of diagnosing liver pathologies, particularly in children versus adults [1:13:15];
    • Comprehensive liver health assessments via imaging and various diagnostic tools to prevent overlooking potential liver pathologies [1:18:45];
    • Potential impact of recreational drugs, statins, and other medications on liver function test results [1:26:45];
    • Shifting nomenclature from NAFLD to MASLD to reflect accuracy in the underlying pathophysiology and understanding of liver diseases [1:30:30];
    • Pathophysiology of MASLD, the need for proactive screening, and the significance of liver fat percentage as an indicator of metabolic health [1:36:30];
    • The importance of screening for rare conditions alongside common metabolic diseases associated with fatty liver accumulation [1:42:45];
    • Practical strategies for managing MAFLD [1:45:30];
    • The impact of fructose consumption on liver health and the challenges of disentangling its effects from other factors like obesity and insulin resistance [1:52:45];
    • The potential of GLP-1 agonists for the treatment of MASLD [1:57:45];
    • How the four stages of liver disease have evolved [2:00:30];
    • Increased cancer and heart disease risk associated with early-stage MAFLD [2:05:15];
    • Emerging drugs and therapies for addressing fat accumulation and fibrosis related to MAFLD [2:12:15];
    • Peter’s major takeaways [2:18:45]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    The Peter Attia Drive
    enMay 20, 2024

    #301 - AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it

    #301 - AMA #59: Inflammation: its impact on aging and disease risk, and how to identify, prevent, and reduce it

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    In this “Ask Me Anything” (AMA) episode, Peter delves into the often misunderstood concept of inflammation. He first defines inflammation and differentiates between acute inflammation and chronic inflammation, the latter of which is linked to aging and a plethora of age-related diseases. Peter breaks down the intricate relationship between chronic inflammation, obesity, and metabolic health, and highlights the signs that might suggest someone may be suffering from chronic inflammation. From there, the conversation centers on actionable advice and practical steps one can take to manage and minimize chronic inflammation. He explores how diet plays a crucial role, including the potential benefits of elimination diets, and he examines the impact of lifestyle factors such as exercise, sleep, and stress management. Additionally, he discusses the relevance of food inflammatory tests and concludes by examining the potential benefits and drawbacks of drugs and supplements in managing inflammation.

    If you’re not a subscriber and are listening on a podcast player, you’ll only be able to hear a preview of the AMA. If you’re a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #59 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here.

    We discuss:

    • Defining inflammation (and the cultural impact of Napoleon Dynamite) [1:45];
    • Acute vs chronic inflammation [8:00];
    • The connection between chronic inflammation, aging, and age-related diseases [11:00];
    • The impact of inflammation on metabolic health [18:30];
    • Understanding and diagnosing chronic inflammation: blood tests and other approaches, and challenges with measurement [20:00];
    • Factors that contribute to low-level chronic inflammation [28:00];
    • Minimizing inflammation through diet [29:45];
    • The important role of fiber for gut health and inflammation [33:45];
    • A closer look at the impact of trans fats and saturated fats on overall health [34:45];
    • Why Peter prefers dietary fiber from food sources over supplements [38:30];
    • Debunking “superfoods”: emphasizing proven methods over marketing claims for reducing inflammation [39:00];
    • Is there any value in over-the-counter food inflammatory tests? [42:30];
    • Food elimination diets: how they work, symptoms and markers to watch, challenges and limitations [45:15];
    • Identifying dietary triggers for gut-related symptoms through low-FODMAP diets like the “carnivore diet” [51:15];
    • Dairy: the complex role of dairy on inflammation and individual responses [55:00];
    • Wheat: the complexities and conflicting evidence around wheat's inflammatory effects [57:45];
    • How exercise influences inflammation [1:02:00];
    • How sleep quality and duration impacts inflammation [1:07:00];
    • The potential impact of chronic psychological stressors on inflammation [1:13:00];
    • The impact of oral health on inflammation and overall well-being [1:15:00];
    • The role of medications in managing chronic inflammation [1:18:15];
    • Supplements: evaluating the efficacy of various anti-inflammatory supplements [1:22:15];
    • Parting thoughts and takeaways [1:27:00]; and
    • More.

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    The Peter Attia Drive
    enMay 13, 2024

    #300 - Special episode: Peter on exercise, fasting, nutrition, stem cells, geroprotective drugs, and more — promising interventions or just noise?

    #300 - Special episode: Peter on exercise, fasting, nutrition, stem cells, geroprotective drugs, and more — promising interventions or just noise?

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    In this special edition celebrating 300 episodes of The Drive, Peter discusses a variety of popular topics and health interventions and classifies them based on their level of evidence and relevance using the following categories: proven, promising, fuzzy, noise, and nonsense. Peter first delves into the topic of geroprotective molecules, covering rapamycin, metformin, NAD and its precursors, and resveratrol. Next, he explores the significance of metrics like VO2 max and muscle mass, as well as emerging concepts like blood flow restriction and stem cells. The conversation extends to nutrition, addressing questions surrounding long-term fasting, sugar consumption, sugar substitutes, and the contentious role of red meat in cancer. Peter not only provides his current stance on each topic—most of which have been covered in great detail in the previous 300 episodes—but also reflects on how his opinion may have evolved over the years.

    We discuss:

    • Defining the categories of “proven, promising, fuzzy, noise, and nonsense” [3:15];
    • Rapamycin [9:30];
    • Metformin [17:00];
    • NAD and its precursors [24:30];
    • Resveratrol [32:45];
    • The importance of VO2 max, muscle mass, and muscular strength for lifespan [38:15];
    • Blood flow restriction (BFR) training [44:00];
    • Using stem cells to treat osteoarthritis or injury [51:30];
    • Fasting as a tool for longevity (and why Peter stopped his fasting protocol) [55:45];
    • The energy balance theory [1:06:30];
    • The idea that sugar is poison [1:12:00];
    • The idea that sugar substitutes are dangerous [1:22:15];
    • The debate on red meat and cancer [1:28:45]; and
    • More.

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    Special episode with Dax Shepard: F1 and the 30th anniversary of Ayrton Senna’s death

    Special episode with Dax Shepard: F1 and the 30th anniversary of Ayrton Senna’s death

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    This is a special episode of The Drive with Peter’s friend and fellow car enthusiast Dax Shepard. In this podcast, which commemorates the 30th anniversary of the death of Brazilian Formula One legend Ayrton Senna, Dax sits down with Peter to better understand what made Senna so special and why Peter remains an enormous fan. This conversation focuses on Senna’s life, the circumstances of his death, and his lasting impact and legacy on the sport of F1.

    We discuss:

    • Peter’s interest in motorsports began as a child [2:30];
    • The drama and dangers of F1 [6:00];
    • What made Senna special [13:00];
    • What Senna meant to Brazilians [24:00];
    • The cause of the fatal crash [28:15];
    • Why Peter is obsessed with Senna [40:30];
    • Being the best versus having the best record [43:30];
    • Senna’s unique driving style and incredible intuition about automotive engineering [46:30];
    • Back to the day of the dreadful race [53:00];
    • What Peter believes caused the crash [1:02:45];
    • Views on dying young, in the prime of life [1:13:00];
    • Senna lives on in his foundation and in safety changes adopted by F1 [1:21:00];
    • Statistics aren’t enough for fandom, and why people like who they do [1:24:15];
    • The biggest difference between F1 today and F1 in the 80s [1:28:30];
    • Senna’s driving superpower [1:30:30];
    • The fastest drivers currently in F1 [1:38:30];
    • Current F1 obsessions [1:45:00];
    • How hard it is to do what the top F1 drivers do [1:50:15];
    • Dax’s love of motorcycles and his AMG E63 station wagon [1:52:15];
    • Awesome Senna mementos from Etsy [2:01:15];
    • What makes specialists interesting, and Max’s devotion to F1 [2:10:15];
    • What Senna might have done if he had not died that day [2:14:00];
    • Michael Schumacher and Max Verstappen are also top F1 drivers [2:17:30];
    • Interlagos in Sao Paulo Brazil is always an incredible experience [2:18:45]; and
    • More.

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    #299 ‒ Optimizing muscle protein synthesis: the crucial impact of protein quality and quantity, and the key role of resistance training | Luc van Loon, Ph.D.

    #299 ‒ Optimizing muscle protein synthesis: the crucial impact of protein quality and quantity, and the key role of resistance training | Luc van Loon, Ph.D.

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    Luc van Loon is an internationally renowned expert in skeletal muscle metabolism. In this episode, Luc starts with an exploration of the roles of insulin and triglycerides in endurance exercise, highlighting their impact on skeletal muscle metabolism, and he offers profound insights into the significance of protein in this context. He elucidates how different protein types and forms influence muscle protein synthesis rates, exploring the nuances of protein absorption, digestibility, amino acid quality, and their implications for performance and recovery. Delving deeper, he differentiates between animal and plant protein sources, unraveling the distinctive properties of various protein types, from the differences between whey and casein to the emerging trends in collagen protein supplementation. Moreover, Luc dissects the intricate connections among physical activity, lean muscle mass, muscle protein synthesis induced by resistance training, and dietary protein.

    We discuss:

    • Luc’s background and insights about fuel selection during exercise [3:30];
    • Fuel utilization during endurance exercise [9:30];
    • Fat metabolism, intramuscular lipids, and the nutritional dynamics of endurance sports [17:15];
    • The optimal window for replenishing intramuscular fat stores and glycogen post-exercise [25:15];
    • Luc’s interest in protein metabolism and exploration of amino acids' dual role as building blocks and signaling molecules in driving muscle protein synthesis [32:15];
    • How protein metabolism differs between sedentary individuals and those engaged in predominantly strength training or endurance training [38:45];
    • The basics of how proteins are digested and absorbed, and how muscle protein synthesis is measured [50:30];
    • How factors like food texture, cooking methods, and protein composition impact muscle protein synthesis, and the importance of protein distribution throughout the day [59:45];
    • Differences in whey and casein proteins, and the ability of ingested protein to stimulate muscle protein synthesis [1:03:30];
    • Dietary protein distribution and quantity for the maximization of muscle protein synthesis [1:09:00];
    • Muscle loss with age and inactivity and the importance of resistance exercise to maintain type II muscle fibers [1:17:15];
    • Differences between whey and casein proteins, and the importance of both quantity and quality of protein sources [1:28:30];
    • Optimizing muscle protein synthesis: exercise, timing of protein intake, protein quality, and more [1:37:00];
    • How to preserve muscle while trying to lose weight [1:46:00];
    • Anabolic resistance and overcoming it with physical activity [1:55:45];
    • Importance of protein intake and physical activity in hospitalized patients [2:06:30];
    • Reviewing the efficacy of collagen supplements [2:13:30];
    • Plant-based diets: how to ensure a balance of amino acids, and other considerations [2:20:30];
    • Future research: understanding protein metabolism in the brain [2:23:45]; and
    • More.

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    #298 ‒ The impact of emotional health on longevity, self-audit strategies, improving well-being, and more | Paul Conti, M.D.

    #298 ‒ The impact of emotional health on longevity, self-audit strategies, improving well-being, and more | Paul Conti, M.D.

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    Paul Conti is an author and practicing psychiatrist who specializes in helping people heal from trauma. In this episode, Paul returns to The Drive to delve into the intricate relationship between emotional health, healthspan, and lifespan. He first challenges common assumptions about the inevitable decline of emotional health with age, providing strategies for conducting a comprehensive audit of internal emotional health. He establishes a framework for the foundation of good emotional health: a balance between the generative drive, the assertive drive, and the pleasure drive. Paul also explores the nuanced dynamics of motivation, happiness, and satisfaction as it relates to material possessions, draws connections between physical and emotional well-being, confronts the impact of negative self-talk, and describes how making peace with our mortality can foster a sense of hope, purpose and well-being. Additionally, Paul offers many practical insights into initiating emotional health improvements and navigating the search for a suitable therapist.

    We discuss:

    • The importance of prioritizing emotional health as we age [2:45];
    • The impact of emotional health on healthspan and how to foster a proactive approach to emotional well-being [7:00];
    • The discrepancy between outward success and inner fulfillment, and the importance of a healthy “generative drive” for genuine well-being [13:00];
    • A deeper dive into generative drive: impact on human behavior, resilience, purpose, and more [23:15];
    • Evaluating one’s inner self: introspection, self-awareness, challenging societal norms, and returning to the basics of physical and emotional well-being [29:00];
    • Self-auditing tools: introspection, curiosity, and exploring underlying reasons for unwanted behaviors [41:45];
    • Breaking free from destructive cycles by understanding the continuum of self-care and addictive behaviors and remaining curious [50:15];
    • Critical self talk: the malleability of one’s inner dialogue and the potential for transformative change with perseverance and self-compassion [1:00:15];
    • Slowing the anger response and gaining insights into the underlying triggers to achieve lasting change and self-understanding [1:13:45];
    • Foster gratitude and humility by achieving balance between the three drives—assertion, pleasure, and generative [1:20:45];
    • The conflict between intellectual understanding and emotional feelings, problematic comparison frameworks, and the importance of living in the present with intentionality [1:24:15];
    • How making peace with our mortality can foster a sense of hope, purpose and well-being [1:34:45];
    • Advice for finding a compatible therapist [1:43:45];
    • The key components of therapeutic progress [1:57:00];
    • The caricatures of four common patient phenotypes, and how to get through to them [2:05:30];
    • How Paul manages his own well-being and the emotional challenges that come with his line of work [2:15:15]; and
    • More.

    Connect With Peter on TwitterInstagramFacebook and YouTube

    Related Episodes

    #108 Metabolic Health: What You Need to Know with Dr. Brian Lenzkes

    #108 Metabolic Health: What You Need to Know with Dr. Brian Lenzkes

    In this episode of Hart2Heart, host Dr. Mike Hart sits down with Dr. Brian Lenzkes, an internal medicine doctor and host of the low-carb MD podcast, to discuss the often misunderstood world of metabolic health. Together they discuss the benefits of intermittent fasting and ketogenic diets to the pitfalls of traditional healthcare, Dr. Lenzkes shares his journey toward a more personalized approach to medicine. They explore the root causes of metabolic diseases, the importance of lifestyle changes, and the limitations of relying solely on medication. 

    Show Notes:

    [0:00] Welcome back to the Hart2Heart Podcast with Dr. Mike Hart. Dr. Hart welcomes guest, Dr. Brian Lenzkes to the listeners.    

    [0:30] Low-Carb MD Podcast 

    [1:00] Question: Can you tell the listeners a bit about yourself?

    [2:00] The shift to direct primary care is discussed

    [3:45] Question: Can you explain what being metabolically healthy means and why are we doing such a poor job of it?

    [4:40] Five key factors for a long, healthy life

    [7:30] Question: When someone is metabolically unhealthy, what are they mostly at risk of acquiring?

    [10:00] The dangers of visceral fat are explained

    [12:15] Parameters for metabolic health

    [15:30] What is CRP

    [19:00] The role of statin drugs in managing cardiovascular health

    [26:00] The value and importance of a sense of community in medical practice 

    [29:40] Metformin and Berberine 

    [34:30] The crucial role stress and sleep play in one's metabolic health

    [41:25] Muscle mass and metabolic health

    [52:10] The link between testosterone and metabolic health

    [56:00] Men's Health vs. Women's Health with Dr. Jaime Seeman aka Dr. Fit and Fabulous

    [58:00] Connect with Dr. Brian Lenzkes on twitter @BrianLenzkes, on IG @blenzkes at his website https://sandiegometabolichealth.com/brian-lenzkes-md/, and his podcast  Low-Carb MD Podcast

    ---

    Dr. Mike Hart is a Cannabis Physician and Lifestyle Strategist. In April 2014, Dr. Hart became the first physician in London, Ontario to open a cannabis clinic. While Dr. Hart continues to treat patients at his clinic, his primary focus has shifted to correcting the medical cannabis educational gap which exists in the medical community. 

    Social Links:

     

    Dr. Nir Barzilai: Can This Drug Slow Aging? The Science Behind Metformin

    Dr. Nir Barzilai: Can This Drug Slow Aging? The Science Behind Metformin

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    Dr. Nir Barzilai is a geroscientist, Chaired Professor of Medicine and Genetics, and the founder and principal investigator of the Einstein Nathan Shock Center and the Glenn Center for Excellence in Biology of Aging. He also studies families of centenarians that have provided genetic and biological insights on the protection against aging—with several drugs developed based, in part, on these paradigm-changing studies. He is also leading the TAME (Targeting/Taming Aging with Metformin) trial to prove to the FDA that aging can be delayed and to allow for next-generation interventions. 


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    In this episode we discuss (audio version / Apple Subscriber version):

    • The hallmarks of aging (9:01 / 7:10)
    • What causes the hallmarks of aging? (15:40 / 13:49)
    • Dr. Barzilai’s research on centenarians (23:16 / 21:25)
    • Why living to 100+ years is good for the economy (24:54 / 23:03)
    • What enables someone to live to 100 years old? (29:30 / 25:20)
    • Taking growth hormone and Metformin have different effects based on your age (36:58 / 32:48)
    • The connection between HDL cholesterol and longevity (43:36 / 39:26)
    • Dr. Barzilai’s research on Metformin (56:23 / 52:13)
    • How Metformin works in the body and on muscle growth (1:04:51 / 1:00:41)
    • Dr. Barzilai’s personal longevity (1:42:05 / 1:37:55)


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    Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects

    Journal Club with Dr. Peter Attia | Metformin for Longevity & The Power of Belief Effects
    In this journal club episode, my guest is Stanford and Johns Hopkins-trained physician, Dr. Peter Attia, M.D., who is also the host of The Drive podcast and the author of the bestselling book "Outlive: The Science & Art of Longevity." We each present a scientific paper and discuss the findings' strengths, weaknesses and actionable takeaways. First, we discuss an article that addresses whether taking the drug metformin can enhance longevity. Then, we discuss an article on belief effects (similar to placebo effects), showing how the effects of a drug on the brain and cognition depend on one's belief about the dose of the drug taken, not the actual dose. Our conversation also highlights how to read, interpret and critique scientific studies. This episode ought to be of interest to those curious about health and longevity, medicine and psychology and for anyone seeking to better understand how to read and digest scientific findings. For show notes, including referenced articles and additional resources, please visit hubermanlab.com. Transcripts are available exclusively for Huberman Lab Premium members. Thank you to our sponsors AG1: https://drinkag1.com/huberman Helix Sleep: https://helixsleep.com/huberman Levels: https://levels.link/huberman InsideTracker: https://insidetracker.com/huberman Momentous: https://livemomentous.com/huberman Timestamps 00:00:00 Dr. Peter Attia, Journal Club 00:03:27 Sponsors: Helix Sleep & Levels 00:06:11 Dreams 00:12:36 Article #1, Metformin, Mitochondria, Blood Glucose 00:19:47 Type 2 Diabetes & Causes, Insulin Resistance 00:25:30 Type 2 Diabetes Medications, Metformin, Geroprotection, Bannister Study 00:36:19 Sponsor: AG1 00:37:15 TAME Trial; Demographics, Twin Cohort 00:44:27 Metformin & Mortality Rate 00:51:28 Kaplan-Meier Mortality Curve, Error Bars & Significance, Statistical Power 01:01:17 Sponsor: InsideTracker 01:02:23 Hazard Ratios, Censoring 01:09:00 Metformin Advantage?, Variables, Interventions Testing Program 01:16:02 Berberine, Acarbose, SGLT2 Inhibitors 01:23:48 Blood Glucose & Energy Balance; Caloric Restriction, Aging Biomarkers 01:32:22 Tool: Reading Journal Articles, 4 Questions, Supplemental Information 01:38:10 Article #2, Belief Effects vs. Placebo Effect 01:45:22 Nicotine Effects 01:51:07 Nicotine Doses & Belief Effects, fMRI Scan 02:00:07 Biological Effects, Dose-Dependent Response & Belief Effects 02:05:14 Biology & Beliefs, Significance, Dopamine Response, Non-Smokers 02:10:57 Dose-Dependence & Beliefs, Side Effects, Nocebo Effect 02:19:06 Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Neural Network Newsletter, Social Media Title Card Photo Credit: Mike Blabac Disclaimer

    #270 ‒ Journal club with Andrew Huberman: metformin as a geroprotective drug, the power of belief, and how to read scientific papers

    #270 ‒ Journal club with Andrew Huberman: metformin as a geroprotective drug, the power of belief, and how to read scientific papers

    View the Show Notes Page for This Episode

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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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    FITNEST MAMA | Everything you need to know about exercise during pregnancy with gestational diabetes

    FITNEST MAMA | Everything you need to know about exercise during pregnancy with gestational diabetes

    We all know we should be doing exercise, right?
    It’s good for our physical health, mental health and your blood sugar.
    So it's a no brainer to fit it into your day, right?

    Except that ... sometimes life gets in the way and sometimes it can be hard, and how the hell are you meant to know what to do when you're pregnant!

    It's not always simple. 

    It's a bit like with food how we all generally know the gist of what’s good for us (moving our body, eating fruits and vegetables), but the tricky thing is actually knowing HOW to do this, and what specifics to focus on in certain times, again, like pregnancy.

    So I get it.

    You might not know what exercises are safe, or what is best to reduce blood sugar.

    OR you might have a decent idea of what you could or want to be doing, but a busy toddler and a full time job take up almost every moment of your time and regularly get in the way.

    This episode is here to demystify exercise for you.

    I had the pleasure of chatting with Kath Baquie,  a mum of 3, a perinatal physiotherapist, and founder of FitNest Mama. She has SO much wisdom around pre and postnatal exercise and I know you'll get a lot out of listening to this!

    We touch on what is safe and recommended, how to overcome barriers to exercise, and the impact on blood sugar.

    Enjoy x 

     

    Make sure you hit SUBSCRIBE so you don’t miss out on any of my free nutrition tips. 

    And if you found this episode helpful, I would be so appreciative of you leaving me a rating and review - it helps this podcast reach other people like you! 

    You can leave a google review here:  https://g.page/r/CT8DWXBPFFFKEAI/review 

     

    Links and resources:

    Thanks for being here x

     

    Disclaimer: 

    The information in this podcast is provided for informational and educational purposes only, and is not a substitute for individualised medical and nutrition advice. Please speak to your healthcare team before making any changes to your diet and lifestyle. Helena (and any guests) do not accept liability for any harm or damages that occur from following suggestions in these podcast episodes.