Summary of 272 ‒ Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more

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00:00:00 - 01:00:00

In this YouTube video, the speakers discuss the potential longevity benefits of rapamycin and its surge in popularity. They explore the robust and reproducible impact of rapamycin on longevity and health span in various organisms, including yeast, worms, fruit flies, mice, and dogs. They emphasize the importance of scientific rigor in studying rapamycin and highlight its evolutionary conservation in promoting longevity. The speakers also discuss the challenges in implementing rapamycin as a longevity treatment, such as determining the optimal time to initiate treatment and the dosing protocol. Overall, the video provides valuable insights into the potential benefits and unanswered questions surrounding rapamycin as a longevity therapeutic.

  • 00:00:00 In this section, the speaker discusses the potential longevity benefits of rapamycin and why it has gained popularity in recent years. The speaker explains that rapamycin is a highly robust and reproducible drug in pre-clinical studies, showing positive impacts on longevity and various aspects of health span. The discussion then transitions to a three-way conversation about rapamycin and mTOR, with the aim of providing a comprehensive explanation of these topics for newcomers. The guests, David and Matt, introduce themselves as leading authorities on rapamycin and mTOR, sharing their expertise and research on the molecule and its mechanism of action.
  • 00:05:00 In this section, Dr. Matt Kaeberlein, a leading authority on rapamycin and mTOR, discusses his background and how he became interested in studying rapamycin's potential as a longevity therapeutic. He explains that his initial discovery of the mTOR gene and its connection to lifespan was accidental, but it sparked his curiosity and led him to explore the effects of rapamycin on various organisms, including yeast, worms, fruit flies, mice, and even pet dogs. Dr. Kaeberlein highlights the robust and reproducible impact of rapamycin on longevity and healthspan and shares his excitement about an ongoing veterinary clinical trial to evaluate its effects in dogs. He also acknowledges his involvement as a funder of the study and emphasizes the importance of taking a scientific approach to studying rapamycin, which has contributed to its growing interest in the field.
  • 00:10:00 In this section, the conversation revolves around the discovery of rapamycin and the importance of scientific rigor in the field. The discovery of rapamycin started with a soil sample collected from Easter Island, also known as Rapa Nui. The bacteria found in the sample eventually led to the isolation of rapamycin. The molecule was initially tested for its immunological and antifungal properties before being pursued as an immunosuppressant. The conversation emphasizes the scientific foundation laid by David in understanding the complex mTOR signaling network and Matt's contribution in applying this knowledge in more clinical contexts. Commercialization of other molecules in the field is criticized, highlighting the credibility and rigorous approach taken by Matt in his research. Overall, the discovery of rapamycin and the scientific rigor in the field are seen as important factors for its credibility and potential longevity benefits.
  • 00:15:00 In this section, the speakers discuss the history and development of rapamycin as well as the challenges it faced in becoming widely accepted. They highlight how the clinical path took too long and how the drug's reputation as a dangerous drug hindered its development for other uses. They also emphasize the importance of understanding the side effect profile of rapamycin at lower doses in patients who are not immunocompromised. The speakers mention the significant time gap between the discovery of rapamycin and its FDA approval in humans. They also discuss the previous use of rapamycin as an immunosuppressant in transplant patients and the toxic side effects associated with it. However, they caution that these side effects may not apply at lower doses in different patient populations.
  • 00:20:00 In this section, the speakers discuss the impact of rapamycin on lifespan and its connection to other organisms. They recall how they initially dosed C. elegans worms with rapamycin, unaware that it would not have an effect due to the worms' cuticle. However, the discovery of the genetics behind aging and rapamycin's effectiveness in other organisms, such as yeast, mice, and flies, created a significant impact. They mention that dietary restriction has also shown to have similar effects in various organisms. The speakers note that rapamycin stands out as a molecule that has consistently increased lifespan and health span across different species. They discuss the genetic inhibition of mTOR that accompanies rapamycin in these studies, solidifying the evidence for mTOR's role in longevity. The conversation highlights the evolutionary conservation of the genetics of longevity and emphasizes the importance of understanding this biology in aging research.
  • 00:25:00 In this section, the speakers discuss the importance of understanding the fundamental processes that impact aging. They highlight that the regulators and impactors of these processes are likely to be conserved across different organisms. They also differentiate between disease-specific strategies that can improve health and lifespan and fundamental approaches that target the pillars of aging. They mention the nine Hallmarks of Aging and the significance of the Nia interventions testing program study, which showed that rapamycin treatment extended lifespan in mice when started in middle age. This finding opened up possibilities for translational applications and treating middle-aged individuals, which is more practical and pragmatic.
  • 00:30:00 In this section, the speakers discuss the potential challenges of implementing rapamycin as a longevity treatment. They mention that inhibiting mTOR, which is the master regulator of nutrient intake, may not be optimal for growing animals like puppies. They also highlight the serendipity that often accompanies scientific discoveries and the unanswered question of why the starting point of delivering rapamycin has an impact on lifespan extension. They note that the optimal time to initiate treatment and dosing protocol for rapamycin in humans is still unknown and may never be fully understood due to the complexity and cost of conducting experiments. However, they argue that funding research on these questions would be worthwhile given the potential benefits and implications.
  • 00:35:00 In this section, the speaker discusses the importance of studying other classes of mTOR inhibitors in comparison to rapamycin. However, they highlight the difficulty in getting funding for these types of studies as they are not considered mechanistic enough by NIH study sections. The speaker also explains the unique mechanism of action of rapamycin, which binds to a protein called FKBP and then targets mTOR. They further delve into the complex role of mTOR, which has various targets involved in cell building (anabolism) and cell breakdown (catabolism), particularly autophagy. The biochemistry of mTOR and its interactions with other proteins are explained to provide a better understanding of its function.
  • 00:40:00 In this section, the speaker discusses the discovery of mTOR complexes and their association with longevity and aging. Initially, it was found that the detergent used to break cells for biochemistry experiments inadvertently broke apart the mTOR complexes. Further research led to the identification of proteins like Raptor and Richter that are connected to lifespan and aging. The mTOR complexes were found to be present in the lysosome, which is responsible for recycling nutrients. The speaker also mentions that mTOR exists in thousands of complexes within a typical cell, with relatively even distribution between mTORC1 and mTORC2. Additionally, mTOR is found in various tissues, including the CNS and even in red blood cells, despite the lack of lysosomes.
  • 00:45:00 In this section, the speaker discusses the mechanism of action of rapamycin, emphasizing that it is an allosteric inhibitor rather than a catalytic inhibitor. Rapamycin binds to mTOR but not in the active phosphorylation region. Instead, it blocks certain substrates from reaching the kinase domain, partially inhibiting mTORC1 and over time, also partially inhibiting mTORC2. The speaker recounts a discovery made by a postdoc who found that rapamycin inhibits mTORC2 and breaks it apart, but initially, the speaker did not believe this to be true. The postdoc's data showed that long-term use of rapamycin can inhibit the phosphorylation of the canonical substrate for mTORC2, akt.
  • 00:50:00 In this section, the researchers discuss the mechanism of action of rapamycin and its potential impact on longevity. They explain that rapamycin prevents the formation of mtorq2 by binding to mtor, thus preventing mtor and Richter from interacting. This prevents the biogenesis of mtorq2 and its subsequent inhibition. They also mention that it is still unclear how rapamycin's inhibition of mtor affects aging biology, and that the assumption that all the benefits come from mtorq1 inhibition and all the side effects come from mtorq2 inhibition is not fully supported by evidence. They suggest that further research is needed to fully understand the mechanisms involved.
  • 00:55:00 In this section, the speaker discusses the activity of mTOR and mTORQ1 and mTORQ2, explaining that they function more like knobs rather than on/off switches. The speaker also mentions the difficulty of conducting a definitive experiment on mTOR due to its complexity and the lack of clean tools. They then dive into the discovery of the localization of mTOR within the cell, mentioning the initial confusion around its specific location and the subsequent finding that mTOR is present in lysosomes. The speaker explains that amino acids play a crucial role in the communication with mTOR, as they cause mTOR to move to lysosomes. Overall, this section highlights the complexity of mTOR and its interaction with nutrients.

01:00:00 - 02:00:00

In this video, the speaker discusses various aspects of rapamycin, including its molecular mechanisms, potential benefits for longevity, effects on muscle mass, tissue-specificity, brain penetration, and its use in treating cognitive impairment and Alzheimer's disease. They also mention the challenges of delivering rapamycin to the brain, its potential effects on amyloid levels, and the complexity of the disease itself. The speaker highlights the breakthrough study that showed rapamycin's rejuvenating effects on the immune system in senior citizens and the subsequent research on rapamycin derivatives, such as everolimus. They also discuss the potential impact of rapamycin on the immune system, epigenome, and various age-related hallmarks. The section concludes with a discussion on the results of a study comparing rapamycin users and non-users, highlighting the lack of significant side effects except for mouth sores. The video raises unanswered questions and potential future research directions for rapamycin.

  • 01:00:00 In this section, the speaker discusses the process of mTOR (mechanistic target of rapamycin) being docked to the surface of the lysosome in the cell. They explain that multiple proteins are involved in this communication process and that it indicates the cell cares about mTOR function. They mention that certain amino acids, such as leucine and arginine, play a role in regulating mTOR activity. The speaker highlights the significance of discovering the receptor for leucine, called sestrin, and describes the crystal structure of leucine bound to sestrin. They mention the challenge of mimicking the effects of leucine due to its specific fit in the receptor's pocket. Furthermore, they raise the question of how long leucine stays in the receptor pocket and suggest that getting leucine out may require an active step. Overall, this section provides insights into the molecular mechanisms involved in mTOR regulation and the role of leucine as a signaling molecule.
  • 01:05:00 In this section, the speaker discusses the complexity of reconciling the benefits of amino acids and mTOR activation with the potential longevity benefits of blocking mTOR. While it is known that amino acids and mTOR activation are important for muscle mass and anabolic processes, studies have shown that rapamycin, an mTOR inhibitor, can actually preserve muscle mass in rodents. However, the exact mechanisms behind this observation are still unclear. One possibility is that rapamycin's anti-inflammatory effects may counteract the potential negative effects on muscle synthesis. The speaker also notes that there is a lack of research on the effects of rapamycin on muscle building in humans, unlike metformin, and further studies are needed to fully understand the relationship between rapamycin, mTOR, and muscle mass.
  • 01:10:00 In this section, the speaker expresses caution in extrapolating findings from mouse studies on sarcopenia to humans, as mice do not develop sarcopenia in the same way as humans. They argue that while protein and amino acid restriction may have positive effects on longevity in mice, it may not have the same benefits for humans who experience sarcopenia to a greater degree. The speaker also raises concerns about the tissue specificity of rapamycin and whether it uniformly blocks mTOR in all tissues. They mention that at higher doses, rapamycin can inhibit mTOR in all tissues, but at lower doses, it is unclear which tissues are most affected.
  • 01:15:00 In this section, the speakers discuss the need for more research on the effects of rapamycin on different tissues and substrates. They suggest that lower doses and intermittent feeding cycles should be explored to better understand the impact on lifespan and healthspan. Additionally, they mention the lack of information on other mTOR substrates and the variations observed in studies conducted so far. There is also uncertainty regarding the brain penetration of rapamycin and whether it is more effective in aging individuals. Overall, more data and research are needed to answer these questions. The physical size of rapamycin is also mentioned, with its molecular weight being around a thousand Daltons, which is larger compared to many other small molecules. However, its size doesn't seem to have a significant impact on its ability to traverse the blood-brain barrier.
  • 01:20:00 In this section, the speakers discuss the challenges of delivering rapamycin to the brain and its potential effects on amyloid levels. They mention a biomarker called c2n that is highly correlated with amyloid in the CNS and share anecdotal evidence of two high-risk patients showing improved c2n scores after taking intermittent rapamycin. However, they acknowledge the limitations of these findings and the need for further research. They also consider the possibility that it may be the peripheral effects of rapamycin that matter for the brain, citing examples of liver-specific knockout leading to partial rescue of a brain disorder and the potential role of systemic immune dysregulation in driving inflammation in the brain. Overall, they suggest that rapamycin's benefits may not necessarily depend on high levels of brain penetration.
  • 01:25:00 In this section, the speaker discusses the use of rapamycin in patients with mild cognitive impairment (MCI) and Alzheimer's disease. They acknowledge the uncertainty surrounding its effectiveness and the complexity of the disease itself. However, they highlight the potential benefits of rapamycin in reducing inflammation and improving autophagy, suggesting that it may have some therapeutic value. The slow timeline for rapamycin's transition into human studies and its lack of profitability resulted in a relative lack of interest in studying rapamycin. Instead, other drugs like everolimus were explored, which are derivatives of rapamycin with slight modifications. These derivatives, known as rapalogs, have similar biochemical mechanisms of action but differ in factors such as bioavailability and tissue distribution. The discussion also touches on the expensive cost of rapamycin, even as a generic drug, indicating the limited alternatives available.
  • 01:30:00 In this section, the speaker recalls the moment when they received a paper challenging the idea that rapamycin would not be a beneficial drug for humans. This paper, written by Joan Mannick and others, showed that rapamycin could rejuvenate the immune system in senior citizens, marking a significant milestone in the field of aging research. The study demonstrated that rapamycin could improve the response to flu vaccination in older mice, ultimately protecting them from a lethal dose of the virus. This breakthrough study paved the way for further research and the possibility of rapamycin being approved as a gerotherapeutic drug for humans.
  • 01:35:00 In this section, the discussion revolves around a study that tested the effects of everolimus (a rapamycin derivative) on the immune response of older adults to a flu vaccine. The study involved three different dosages of everolimus given for six weeks, followed by the vaccine. The results showed that the five milligrams once a week and one milligram daily doses of everolimus increased the antibody response to the vaccine, suggesting that rapamycin derivatives could potentially rejuvenate the immune system in elderly individuals. Importantly, the study also found that these doses were well-tolerated with minimal side effects. This study prompted the idea that lower doses of rapamycin could be beneficial for older adults without causing significant adverse effects. Furthermore, the conversation acknowledges that rapamycin, despite being initially developed as an immunosuppressant, can be more accurately considered an immune modulator, as it can both enhance and suppress different aspects of the immune system. The discussion also acknowledges that rapamycin is no longer commonly used as an immunosuppressive drug in current medical practice, except for legacy patients from decades ago.
  • 01:40:00 In this section, the discussion revolves around the potential impact of rapamycin on the immune system and the epigenome. The speakers debate whether rapamycin, an immunosuppressant, truly increases the risk of infections and whether it can reverse biological aging by changing the methylation patterns in T cells. While there is agreement that rapamycin has some effect on the epigenome, there is uncertainty about the accuracy of current epigenetic clocks in measuring biological aging. Additionally, the speakers share their findings that rapamycin primarily affects cell cycle delay rather than specific methylation patterns. However, they acknowledge the dramatic improvements seen in the immune system of older mice after just six weeks of rapamycin treatment, which suggests a more profound impact beyond cell cycle regulation.
  • 01:45:00 In this section, the conversation revolves around the link between rapamycin and epigenetic changes. The participants express differing opinions on whether there is a specific signal transduction pathway from mTOR to an epigenetic state. They also discuss the impact of rapamycin on various age-related hallmarks, with the consensus being that while the link between rapamycin and epigenetics is weaker than other hallmarks, rapamycin still has the potential to impact epigenetic changes with aging. Additionally, they speculate on the potential of rapamycin to reset the immune system and improve its response to vaccines, suggesting that the observed rejuvenating effects of rapamycin may not solely be due to epigenetic changes. The section concludes with a mention of a survey conducted on rapamycin users, highlighting the limitations of self-reported data but suggesting potential benefits associated with rapamycin use.
  • 01:50:00 In this section, the speaker discusses the results of a study comparing rapamycin users and non-users. They found that non-users were similar to users in terms of demographics and lifestyle habits, indicating a biased cohort of health-conscious individuals. The study found no significant side effects of rapamycin except for mouth sores, which were more common among users. The speaker suggests that the mouth sores may be a result of the rapid turnover of epithelial cells and the slowing down of cell proliferation caused by rapamycin. They also discuss the possibility of using FK 506 mouthwashes as a way to prevent the mouth sores, as FK 506 can occupy the same binding sites as rapamycin without inhibiting mTOR.
  • 01:55:00 In this section, the discussion revolves around the potential benefits and unanswered questions regarding the use of rapamycin. One interesting experiment that is suggested is delivering rapamycin directly to the oral cavity through toothpaste or mouthwash to determine if it can provide similar benefits as systemic treatment on periodontal disease and inflammation. The topic of rapamycin's effects on depression and anxiety is also explored, with the possibility that it may have some beneficial effects in certain individuals. Additionally, the combination of rapamycin with ketamine is discussed, with some anecdotal evidence suggesting positive outcomes in patients with severe chronic pain. However, the details and mechanisms of this combination therapy require further study. Other findings from the survey include a potential correlation between rapamycin use and a lower risk and severity of COVID-19, but confounding factors need to be considered.

02:00:00 - 03:00:00

This video discusses various aspects of rapamycin, including its potential benefits, ongoing clinical trials, dosing protocols, and funding challenges. One study found that rapamycin may have a positive impact on the severity of COVID-19 infection and the likelihood of long COVID symptoms. However, more research is needed to confirm these findings. The video also talks about the potential benefits of rapamycin in achieving a state that cannot be achieved through dietary interventions alone, the use of RTB 101 and its efficacy, the pathways affected by mTOR inhibition, ongoing clinical trials in companion animals, and the importance of considering health span metrics in addition to lifespan. The speakers express frustration with the slow progress in funding and conducting clinical trials, emphasizing the need for larger trials and more investment in this field.

  • 02:00:00 In this section, the speaker discusses a study on the impact of rapamycin on COVID-19 infection and its severity. The study included three categories of people who used rapamycin: those who started after their infection, those who took it before but not during, and those who took it continuously. The results showed no significant difference in the likelihood of getting a positive COVID-19 result among rapamycin users. However, statistically significant differences were observed in the severity of infection and the likelihood of long COVID symptoms. People who took rapamycin throughout had lower severity of infection and lower likelihood of long COVID symptoms. The speaker suggests that rapamycin's potential benefits may be associated with its ability to modulate the hyperinflammatory response seen in severe COVID-19 infections. It is worth noting that further research is needed to confirm these findings. The speaker also shares that they personally have not taken rapamycin, but their decision is not due to fear, but rather the effort required and uncertainty about whether the benefits outweigh the cost.
  • 02:05:00 In this section, the speaker discusses the potential benefits of using rapamycin or other mTOR modulators for achieving a state that cannot be achieved through dietary interventions alone. They mention that dietary interventions can only go so far in terms of depriving cells of nutrients, whereas rapamycin or catalytic inhibitors may have a more significant impact on the system by activating autophagy and rewiring it. However, the speaker also acknowledges that catalytic inhibitors can be highly toxic and have many side effects, so careful consideration is needed when studying their potential use. Additionally, another speaker highlights that dietary restriction has its own unique benefits that rapamycin doesn't provide, and these factors should also be taken into account when comparing the two. Finally, they mention that catalytic inhibitors can affect other kinases and proteins, making them less specific for mTOR.
  • 02:10:00 In this section, the speakers discuss the molecule RTB 101 and its potential as a clinical treatment. While RTB 101 falls into the ATP competitive mTOR inhibitor class, it also inhibits other kinases, which makes its specificity and side effect profile unclear. However, in studies conducted by Joan at restore bio, RTB 101 was dosed in individuals without significant side effects. The trial was shut down, but there is some belief that the molecule may have efficacy when used clinically at certain doses. The speakers also mention the need for further research to compare the relative benefits and side effect profiles of different mTOR inhibitors in animal models. They suggest that rapamycin may not necessarily be the best in class and that other molecules may work better, emphasizing the importance of understanding the biology of these inhibitors in the context of aging.
  • 02:15:00 In this section, the speaker discusses the reasons behind the use of rtb 101 in the clinical trials and the absence of everolimus. The decision to use rtb 101 was based on its potential to induce antiviral gene expression, enhance vaccine response, and improve resistance to subsequent infections. The pivotal phase three trial, which used rtb 101 alone, was only half completed and was stopped due to the failure to meet the FDA mandated endpoint of patient reported infections. Although the trial was deemed a failure in terms of FDA approval, subsequent analysis showed that patients who received rtb 101 had a significantly lower risk of future laboratory confirmed viral infections. However, it remains unclear whether the failure was due to the drug itself or other factors. The speaker also speculates that the decision to exclude everolimus may have been influenced by patent life considerations.
  • 02:20:00 In this section, the discussion centers around the various pathways affected by mTOR inhibition and rapamycin. The impact of autophagy, reduction of inflammation, and suppression of senescent cells are highlighted as potential mechanisms driving the longevity benefits of rapamycin. While autophagy is seen as a prominent pathway influenced by mTOR inhibition, it is acknowledged that mTOR has a broad range of downstream effects, making it difficult to pinpoint one specific pathway responsible for rapamycin's effects on aging. The analogy of an old house needing multiple repairs is used to illustrate the complexity of the aging process, suggesting that the multifaceted nature of mTOR's actions may be crucial in targeting the aging process.
  • 02:25:00 In this section, the speakers discuss the potential longevity benefits of rapamycin and its different downstream effects. They mention that while autophagy is an important downstream process regulated by mTOR, the anti-inflammatory effects of rapamycin may account for most of the functional benefits seen in treating old organisms. It is noted that the specific effects of mTOR may vary in different tissues and pathologies. The speakers also discuss the need for biomarkers of inflammation and the lack of biomarkers for autophagy. They then pivot to talk about the study of rapamycin in companion animals, specifically cats and dogs, stating that they age more rapidly than humans, making it easier to measure outcomes of interest. The researchers emphasize the value of developing therapies to improve the health span and longevity of companion animals.
  • 02:30:00 In this section, Dr. Matt Kaeberlein discusses the ongoing clinical trial called the Test of Rapamycin and Aging Dogs. The trial aims to assess the effects of rapamycin on lifespan and health span metrics in companion dogs. The trial is double-blind, randomized, and placebo-controlled, with a treatment period of three years. The primary endpoint is lifespan, and the cohort of 580 dogs is powered to detect a nine percent change in lifespan. The dogs must be at least seven years old and free from significant age-related diseases. Dr. Kaeberlein also mentions that big dogs age faster than small dogs, so the trial focuses on dogs weighing between 40 and 110 pounds. The results of this study, along with other research in the field, will provide valuable insights into the potential longevity benefits of rapamycin for both humans and animals.
  • 02:35:00 In this section, the speakers discuss the potential longevity benefits of rapamycin and the importance of considering health span metrics rather than just lifespan. They express confidence that rapamycin is unlikely to shorten lifespan, based on previous data in mice and dogs. They also mention an ongoing study in marmosets, a non-human primate model, which has shown preliminary data suggesting positive survival effects from rapamycin. However, they acknowledge the limitations of the study being done in captivity and highlight the importance of future studies in free-living animals. The dosing for their own study is mentioned as 0.15 milligrams once a week. Overall, they recognize the need for comprehensive evaluation of rapamycin's efficacy on both lifespan and health span metrics.
  • 02:40:00 In this section, the speaker discusses the dosing protocol for the clinical trial and the factors that influenced the decision. They mention that once weekly dosing of everolimus seemed to have similar efficacy with lower potential side effect risks, making it a pragmatic choice for the trial. However, the speaker expresses concern that the dose may be too low and that they may be dosing below the level needed to see statistically significant effects. They also compare the dosing in mouse studies and note that intermittent dosing may have beneficial effects in larger animals. The speaker mentions that in a survey, the majority of rapamycin users were on a once-weekly dose of six milligrams.
  • 02:45:00 In this section, the speaker discusses the dosages of rapamycin that are popular among off-label users. The standard dose seems to be around 6 milligrams once a week, with some variation among individuals. However, there are also reports of higher doses, such as 20 milligrams once a week, although it is uncertain how long people have been taking rapamycin at those levels. It is important to note that the dosing regimens and concentrations of rapamycin can vary, particularly when using compounded formulations, which may have lower bioavailability. The speaker advises caution when considering compounded rapamycin and suggests opting for FDA-approved options like serulimus or rap immune instead. The lack of funding and profit motive for research in this area is lamented, potentially hindering further exploration and understanding of rapamycin's potential benefits.
  • 02:50:00 In this section, the speakers discuss the potential impact of rapamycin on ovarian aging and spermatogenesis. Studies in mice suggest that transient rapamycin treatment can delay or reverse ovarian atrophy, potentially restoring reproductive capacity in female mice. However, in male mice, rapamycin seems to impair spermatogenesis and may lead to sterility. The speakers speculate that this difference may be due to rapamycin's impact on rapidly proliferating cells, which are more involved in spermatogenesis than oogenesis. They also mention ongoing human studies, including a clinical trial in Colombia, to investigate the effects of rapamycin on fertility biomarkers. However, no data are available yet, and the funding for such studies is often limited to smaller grants rather than large sums of money.
  • 02:55:00 In this section, the speaker expresses frustration with the slow progress in funding and conducting clinical trials for rapamycin. They highlight the underpowered nature of the trials and the lengthy process of obtaining grants, leading to delays in finding answers. The speaker emphasizes the need for larger trials and a more accelerated path for research. They also mention the changing landscape of targeting mTOR, with a shift in consensus towards its importance as a target. Additionally, the speaker suggests exploring other targets in the pathway that may be more beneficial, beyond rapamycin and its derivatives. Overall, they express a desire for more investment and exploration in this field.

03:00:00 - 03:00:00

In the video titled "272 - Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more," the speakers express their interest in continuing the discussion on fascinating biology questions regarding longevity in a public setting. They consider the idea of doing a second part of the discussion before their planned trip to Rapa Nui in 2026. The speakers also express their enjoyment of the conversation and suggest the possibility of meeting in person for the next discussion. However, they mention that a desired plaque was stolen from a specific location they wanted to visit, but they remain determined to still go there.

  • 03:00:00 In this section, the speakers express their desire to continue the discussion on interesting biology questions related to longevity publicly. They mention the possibility of doing a part two of the discussion before their planned trip to Rapa Nui in 2026. They also express their enjoyment of the conversation and suggest the idea of meeting in person for the next discussion. However, they also note that a plaque they wanted to see in a particular place was stolen, but they still plan to visit it.

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