Newly Discovered Cause of Premature Aging - Longevity Scientist Dr. Hariri

Intro (0s)

• We age primarily by damaging core systems like the circulatory system, and glucose plays a significant role in this process, with high blood sugar being linked to insulin resistance and the accumulation of senescent cells (11s).
• Senescent cells are defined as cells that have aged normally, reached the end of their lifespan, and stopped dividing, switching to a phenotype that produces pro-inflammatory and potentially cancer-causing signaling molecules (44s).
• These cells must be cleared to allow for normal repair and replacement, as they secrete toxic chemicals that disrupt tissue and organ function, contributing to unhealthy aging and inflammation (1m31s).
• Senescent cells, also known as "zombie cells," play a positive role in younger individuals, particularly in tissue remodeling and renovation, such as the separation of fingers in a developing fetus (2m33s).
• The process of senescent cells helping with tissue remodeling can be compared to the use of scaffolding in construction, where the scaffold is necessary for building a structure but is eventually torn down once the main structure is complete (3m23s).
• Dr. Bob Hariri's description of glucose as a "broken shard of glass" in the circulation highlights the dangers of high blood sugar and its impact on the body (16s).
• The connection between insulin resistance, high blood sugar, and senescent cells is a significant area of study in the field of longevity (22s).
• Senescent cells are not all the same age or functional level, and they play a role in the continuum of cell development and tissue remodeling throughout an individual's life (2m36s).

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Senescent Cells (4m58s)

• Senescent cells can be thought of as a clone of oneself that initially helps with tasks, but eventually becomes problematic and deleterious to one's life when they become dysfunctional, similar to a clone that starts causing trouble by having an affair with one's spouse (4m58s).
• Senescent cells are helpful to a certain degree, but when they get out of hand or become more dysfunctional with age, they become problematic and need to be cleared (5m40s).
• The elimination of senescent cells can be likened to demolition work that needs to be done to renovate a house, making room for new, healthy, and young cells to replace the broken structures (6m6s).
• Targeting and getting rid of senescent cells allows for renewal and renovation with healthy cells, making room for new growth (6m18s).

Glucose Control for Longevity (6m32s)

• Senescent cells are cleared from the body through the activity of natural killer cells, a specialized form of white blood cell that is part of the innate immune system, which attacks and destroys cells that exhibit abnormal behavior due to infection, cancer, or other reasons, indicated by the expression of stress antigens on their surface (6m57s).
• Natural killer cells track and surgically remove cells with these stress antigens, and maximizing natural killer cell function is crucial for maintaining health and longevity (7m42s).
• One way to maximize natural killer cell function is to keep glucose levels low, as high glucose levels can inactivate natural killer cells, which is associated with damage to the immune system and increased risk of infections and diseases (8m7s).
• Keeping hemoglobin A1c levels low, which is a marker of glucose control, is critically important for maintaining high-performance immune function and preserving natural killer cell function (8m30s).
• New drugs like GLP1 agonists can help achieve better glucose control, which can have benefits for health and longevity by maintaining high-performance immune function and preserving natural killer cell function (8m39s).
• GLP1 receptor agonists have been around for a while and can play an interesting role in controlling glucose levels, and other tools like metformin have also been associated with benefits in lifespan and health by improving insulin sensitivity and keeping circulating glucose levels low (9m26s).
• Metformin has been shown to have benefits in lifespan and health by improving insulin sensitivity and keeping circulating glucose levels below a threshold that glycosites proteins, protecting against the negative consequences of diabetes (9m31s).
• Even athletes who require high glucose levels for optimal performance may need to balance this with the negative consequences of high glucose levels on health and longevity, as seen in extreme examples like Tour de France athletes who keep their blood sugar levels high during rides for extra performance (10m11s).
• High blood glucose levels may not negatively impact longevity in individuals with a normal pancreas, as the body tends to store excess glucose rather than keeping it in circulation, especially in highly physically active states (10m39s).
• Even with high glucose utilization, it's challenging to maintain high blood glucose levels due to the release of endogenous insulin, which promotes glucose storage (10m43s).
• Measuring glucose levels using peripheral monitors may not accurately reflect long-term consequences, and glucose levels may return to normal quickly in highly physically active individuals (11m8s).
• Peripheral insulin resistance can occur during intermittent fasting or a ketogenic diet, leading to temporary increases in glucose levels, but this is not pathological and may not affect overall insulin resistance or HbA1c levels (11m34s).
• Insulin itself, independent of glucose levels, may not play a significant role in NK cell function, as the data suggests that only free glucose levels above a certain threshold can decrease NK cell activity and inhibit their function (12m12s).
• NK cells are affected by the surrounding glucose environment, and high free glucose levels can profoundly inhibit their function, even if insulin levels are not elevated (12m27s).

Optimal HbA1c Level (12m36s)

• Bloodborne markers in the blood are snapshots and do not necessarily reflect long-term exposure to free glucose that an NK cell has experienced (12m38s).
• Hemoglobin A1c (HbA1c) is the best long-term measure of glucose control, and people with high HbA1c levels have decreased NK function, which has negative consequences (12m52s).
• The lower the HbA1c level, the better, and even within the healthy range, there is a difference in NK function, with lower levels being beneficial (13m13s).
• A HbA1c level of 5.7 is considered a threshold, and it is argued that the lower the level, the better, with benefits not just for NK cells but also for a general reduction in exposure to free glucose (13m31s).
• Lower HbA1c levels are associated with improved liver and renal functionality, and it is suggested that keeping glucose burden down, as reflected in a lower HbA1c, is beneficial (13m50s).
• HbA1c is a measure of glucose control over a long period and does not account for peaks and valleys in glucose levels that occur during the day (14m14s).
• Blood tests, including HbA1c, are snapshots and can be influenced by various factors, such as time of day, diet, and activity level, making it essential to consider multiple factors when interpreting results (14m53s).

Glucose Monitors (15m24s)

• Wearable glucose sensors can download enormous amounts of data, which is crucial in medicine as it allows for better trend analysis and management of health variables (15m25s).
• The amount of data generated is important, but managing the trends in that data is more crucial, as seen in aviation where managing trends in turbine pressure is key (15m40s).
• Wearable sensor systems that can monitor 50 or 100 different variables continually and upload them to the cloud for analysis by AI and machine learning are expected to become available in the future (16m7s).
• This technology will enable predictive analysis and allow individuals and AI systems to identify potential health issues before they arise (16m30s).
• A single blood test result can be misleading and may cause unnecessary panic, as it only provides a snapshot of a person's health at a particular point in time (16m37s).
• Repeating a blood test can often provide a different result, and following the trajectory of a change in a value is essential for making accurate diagnostic judgments (17m20s).
• Failing to follow the trajectory of a change in a value can be a disservice to making diagnostic judgments, and it is essential to consider trends in data rather than relying on a single result (17m37s).

The Danger of (high) Glucose (17m47s)

• Keeping glucose levels lower and stable improves longevity by reducing damage to core systems like the circulatory system (17m50s).
• Glucose damages the lining of blood vessels, stimulating an inflammatory response that can lead to scarring and degenerative vascular disease (18m14s).
• Atherosclerosis is considered a degenerative vascular disease, characterized by scarring of the blood vessel wall, rather than just a metabolic or lipid management problem (19m0s).
• Degenerative vascular disease has two pathways: regeneration, where things get fixed to normal, or scarring, which is a hallmark of aging (19m13s).
• Maintaining health as one ages requires stopping anything that creates an inflammatory cascade leading to scarring in blood vessels (19m35s).
• Type 2 diabetes is a higher risk factor for cardiovascular disease, and there is an interplay between the two conditions (19m51s).
• Changes in blood glucose can rapidly affect the ability to fight infection, and high blood sugar can impair immune system function (20m14s).
• In post-operative patients with type 2 diabetes, high blood sugar can lead to abnormal immune system function, making it harder to fight infections (20m22s).
• Controlling blood glucose is crucial in situations like surgical wounds, and can be achieved through insulin, glucose management tools, or other methods (21m18s).
• Keeping glucose under control maximizes the efficiency and effectiveness of the immune system (21m56s).

Should Non-Diabetics Use CGMs? (22m2s)

• There is a common perception that continuous glucose monitoring (CGM) systems are not beneficial for non-diabetic individuals, and may even be harmful if it leads to obsessive eating patterns, but this perspective may be based on a misunderstanding of how to use the data from CGMs (22m3s).
• A more practical approach to using CGMs is to view the data as a tool for understanding overall trends and patterns, rather than obsessing over individual readings, and to use data analysis tools to gain insights from the data (22m26s).
• The use of CGMs can be compared to blood pressure monitoring, where regular monitoring can provide valuable insights into overall health, and can help to identify patterns and trends that may not be apparent from occasional readings (22m51s).
• Mark Twain's quote about "lies, damn lies, and statistics" highlights the importance of using data analysis tools to interpret the data from CGMs, rather than simply looking at individual readings (23m11s).
• The data from CGMs can be skewed if it is only collected in a clinical setting, such as a doctor's office or lab, as this may not be representative of an individual's typical daily patterns (23m50s).
• Continuous monitoring of glucose levels can provide a more accurate picture of an individual's physiology, and can help to identify patterns and trends that may not be apparent from occasional readings (24m7s).
• The use of CGMs is likely to become more widespread and accepted in the future, and may eventually be seen as a standard tool for monitoring health, much like blood pressure monitoring is today (24m19s).

Adopting Aviation Tools (24m43s)

• The adoption of tools from the aviation industry in medicine is necessary to improve healthcare, with the aviation industry having decades of experience in root cause analysis to address problems. (24m43s)
• In advanced aircraft, there are two systems that benefit from this analysis: the master caution button, which indicates an impending problem that needs to be addressed, and the master warning button, which signals a critical issue that requires immediate action. (24m54s)
• Medicine needs a similar system to coalesce and interpret various health data, such as blood glucose, immune cell function, blood pressure, and blood viscosity, to identify potential problems before they become critical. (25m30s)
• A deep analytic tool that can assemble and analyze this information would enable the creation of a strategy to correct problems and prevent them from progressing to irreversible issues. (25m48s)
• The use of AI and machine learning can help absorb and analyze this data in a comprehensive way, and it is expected that the ability to digest this information will improve significantly in the next 5 to 10 years, similar to the advancements in aviation. (26m18s)

Where to Find More of Dr. Hariri (26m41s)

• Dr. Bob Hariri's podcast can be found at pilotinghealth.com, a name that reflects his connection to aviation (26m41s).
• Dr. Bob Hariri can be found on social media under the handle @DrBobHariri (26m50s).
• Dr. Bob Hariri's company can be followed at cellularity.com and Fountain Life can be found at fountainlife.com (26m53s).