Longevity News Blog

I have the world's slowest speed of aging: 0.48 Breaking the 0.5 barrier. This means: + My birthday now happens every 2 years + I am #1 out of 5,677 global Rejuvenation Olympics competitors + My three test average: 0.54This new biological aging measurement science has begun nipping at the heels of the best predictors of all-cause morality. What is the Rejuvenation Olympics? When I started Blueprint, people didn’t know what category to place me so they’d blurt out words like vampire, Patrick Bateman, techbro, f*#@ face, biohacker, Prometheus, Dorian Grey, and more. It was clear that we needed a new category to define what I was doing so I started referring to myself as a “professional rejuvenation athlete”. When LeBron James eats and sleeps well, and then sets records, we praise him. When I did the same, hate rained. Understanding rejuvenation as a sport helps confer some respect and formality to the practice. With this framework, I created the Rejuvenation Olympics. A leaderboard for people who want to compete on their speed of aging, or rather the slowness thereof. Blueprint, Don’t Die and the Rejuvenation Olympics I was doing two things with this. First, up until I started Project Blueprint and Don’t Die, health influencers and health fads were primarily storytelling-based and anecdotal. What was missing: rigorous science, measurement and data. When health decisions are managed by storytelling, it’s hard to know what to do as you never really know what does or doesn’t work and who is or isn’t telling the truth. This led people to be very confused and feel paralyzed. This inspired my project to become the most scientifically rigorous and quantifiable of all time. I became the most biologically measured person in human history. If the goal is don’t die, we need robust, science based systems, with quantifiable results. We built Blueprint on population level scientific evidence. So it’s not an accurate criticism that Blueprint is based upon my biomarkers. Blueprint is for everyone. Yes, each person’s Blueprint can further be customized to your individual needs however the core protocol is applicable to everyone of all ages. The Rejuvenation Olympics set a level playing field for anyone who wanted to compete in health and wellness. Humans love points, status and leaderboards, and these are essential for any competitive sport.  Why your Speed of Aging is important I chose the speed of aging metric because of the robustness and reliability of the signal it measures. DNA methylation is a whole-body health marker that integrates thousands of biochemical cues into a measurable signal. The speed of aging algorithm distills this into a single number: an individual’s PACE score. In just a few years, this new biological aging measurement technology has begun nipping at the heels of the best predictors of all-cause morality. And it’s an easy finger prick at home. When talking about health and wellness, people can compare markers such as blood glucose, hormones, cholesterol and others.  However, each of those are narrow in scope. DNA Methylation, and specifically the clock PACE, is a comprehensive assessment of one’s health.  So I created a new professional sport, gave it a name and rules and created a competition. As you might expect, people are really into it. Are you genetically gifted? From speaking to others on the leaderboard, I’ve learned that some people naturally (genetically) have a very low speed of aging. This makes intuitive sense based upon our life experience. Sometimes people do nothing for their health and are in perfect health. I personally met someone in the top 10 who was fairly close to me in his speed of aging and guess what he does for his health? Nothing. Meanwhile, lowering my speed of aging is a primary focus of my life. He is genetically gifted. I am not. However, even though I’m not genetically gifted, it is interesting that through methodical hard work, one can meaningfully slow down their speed of aging, even outperforming all the genetically gifted ones. When gene editing comes online, perhaps lowering our speed of aging will be a simple fix. Or, maybe it will even be a pill. Until then, I’ve loved playing this game of trying to understand the science, design evidence based protocols, and then execute with precision. The Rejuvenation Olympics has also been incredibly helpful for the entire health community, helping everyone understand what things increase and decrease one’s speed of aging. I’ll post more on this soon. How to compete in the Rejuvenation Olympics: 1. Get a Blueprint Speed of Aging Test. 2. When registering your test, you’ll have the option to participate in the leaderboard. 3. You need three tests to have a “verified” ranking on the leaderboard, and the tests need to be within the previous two years. Your best 3 test results within 2 years will be displayed, allowing for experimentation with various interventions and protocols while not punishing you for the learning process. Be well,Bryan  

Hi Friend, On September 28th, I decided to stop rapamycin, ending almost 5 years of experimentation with this molecule for its longevity potential. I have tested various rapamycin protocols including weekly (5, 6, and 10 mg dose schedules), biweekly (13 mg), and alternating weekly (6/13 mg) to optimize rejuvenation and limit side effects. Despite the immense potential from pre-clinical trials, my team and I came to the conclusion that the benefits of lifelong dosing of Rapamycin do not justify the hefty side-effects (intermittent skin/soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate). With no other underlying causes identified, we suspected Rapamycin, and since dosage adjustments had no effect, we decided to discontinue it entirely. Preclinical and clinical research has indicated that prolonged rapamycin use can disrupt lipid metabolism and profiles [1], as well as induce insulin and glucose intolerance [2] and pancreatic beta-cell toxicity [3].  Despite anecdotal evidence of rapamycin slowing down tumor growth, its effect in inhibiting natural killer cells [4] raises concerns for anti-cancer immune surveillance and cancer risk in the longer run. Additionally, on October 25th, a new pre-print [5] indicated that Rapamycin was one of a handful of supposed longevity interventions to cause an increase/acceleration of aging in humans across 16 epigenetic aging clocks. This type of evaluation is the first of its kind, as most longevity interventions up to date have been tested against one or two aging clocks, leading to invisible biases and potential intended “cherry picking” of favorable clocks for the tested interventions. Longevity research around these experimental compounds is constantly evolving, necessitating ongoing, close observation of the research and my biomarkers, which my team and I do constantly. Be well, Bryan   Sources https://pubmed.ncbi.nlm.nih.gov/12177161/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3384435/#:~:text=(D)%20Chronic%20treatment%20with%20high,rapamycin%20induces%20Klotho%20%5B64%5D https://diabetesjournals.org/diabetes/article/62/8/2674/34093/Evidence-for-Rapamycin-Toxicity-in-Pancreatic https://pmc.ncbi.nlm.nih.gov/articles/PMC4084728/#:~:text=In%20contrast%2C%20rapamycin%20significantly%20inhibited,cells%20in%20rapamycin%2Dtreated%20recipients https://pubmed.ncbi.nlm.nih.gov/39484592/

Want to learn your biological age? And do so using free tests? We’ve got you. Here are 7 free Bioage Fitness tests designed by the Blueprint clinical team that you can do at home. How to complete the Bioage Fitness tests:1: Download the Don’t Die App2: On your profile, go to ‘Measurements’3: Click on the + next to ‘Capabilities’4: Select the fitness assessment you will complete5: You can view the instructions for the fitness assessment in the app. These instructions are also included in this article.6: Enter your results in the Don’t Die App to receive your biological age Bioage Fitness Test Instructions: 1. Continuous Push-UpsObjective: Measure upper body strength and endurance.Goal: Perform as many push-ups as you can without res Instructions: Lie face down on the floor with hands placed slightly wider t\an shoulder-width apart, elbows fully extended. Lower your body until your chest touches the floor, keeping your body in a straight line from head to heels. Note - don’t round your back! Push back up to the starting position. This counts as one push-up. Perform as many push-ups as you can without rest (considered to be holding at the top 3 seconds), maintaining proper form. Record the number of push-ups completed. 2. Mobility Test: Sit Rise Test Objective: Assess flexibility, strength, and balance.Goal: Sit and rise without using your hands, knees, forearms, or side of the legs for support. Instructions: From a standing position, sit down on the floor with legs crossed, without using your hands, knees, forearms, or side of the legs for support. Rise back to a standing position without using any support (this is the goal). If support is needed, the scoring is as follows: Deduct 1 point for each hand, knee, or forearm used going down and up The maximum score is 10. A score of 8 or more is considered ideal. 3. Waist-to-Height Ratio Objective: Assess body fat distribution, metabolic health and risk.Goal: The smaller the ratio between your waist and height, the better. Instructions: Measure your height in centimeters (cm). Measure your waist circumference at the narrowest point between the ribs and the hips in centimeters. Calculate the ratio: Waist Circumference (cm) / Height (cm).  4. Grip StrengthObjective: Assess hand and forearm strength. Correlates with cardiovascular disease risk.Goal: The larger the number, the better Instructions: Use a grip strength dynamometer. Stand upright and hold the dynamometer at your side. Squeeze the dynamometer as hard as you can. Record the highest reading in lb after 3 attempts in each hand 5. Sit and Reach (YMCA)  Objective: Measure flexibility of the lower back and hamstrings.Goal: The further you reach, the better Instructions: Video Sit on the floor with your legs extended straight out in front of you, with approximately 10-12 inches of distance between your feet Place a second tape measure at the 15” mark between the ~5-6 inch mark of the first tape measure (think like you’re making a “T” or a “+” with both tape measures), the zero should be closest to you. Heels should be resting on the first tape measure.   Place one hand on top of the other, palms facing down, and reach forward as far as possible along the measuring line. Hold the stretch for 1-2 seconds. Measure the distance reached by the fingertips. Repeat twice and record the best distance. 6. One-Leg Stand / Balance TestObjective: Measure balance and lower body strength.Goal: The longer you can balance, the better Instructions: Stand with their eyes shut and on one leg with the other leg bent at the knee and lifted off the ground and free floating. Hold this position as long as possible without touching the raised leg to the ground, using external support, or touching their other leg. Record the time you can hold the position in seconds. Perform the test on both legs and record the times.  7. Reaction Time Test Objective: Measure quickness of response to a stimulus.Goal: The smaller the reaction time, the better Instructions: Download the App “Reaction Time & Reflex Test.’ Click on the Game “Lights Out” Start a new test. Place your thumb or finger on the screen to start the countdown. All 5 lights will illuminate. As soon as the lights turn out pull your finger or thumb off the screen. Repeat 5 times and take the best score of the 5 tests. This will be the lowest number.   If you want more comprehensive baseline testing, we got you covered. Blueprint Labs empowers you with data to take control of your health. Blood PanelsTest either 60 or 115 biomarkers with a comprehensive suite of blood and urine tests designed for deep analysis and insights (basic, advanced). MicroplasticsThe world’s first at-home microplastics blood test, enabling you to screen for most common commercial plastics with just a finger-prick (link). Speed of AgingFind out how old you really are, and learn the biological age and health of 11 critical organ systems and how fast or slow your aging (link).

Hi Friend,A new study is out: things that make you age faster, and slower, according to 16 epigenetic age clocks.These interventions demonstrated a significant decrease or slow-down of Biological Aging1. Pharmacological Interventions: Anti-TNF therapy (anti-inflammatory), Metformin (Anti-diabetes, AMPK activation),Ketamin (antidepressant psychedelic, dissociative). 2. Supplements: AC11 supplement (natural DNA repair booster), TruLacta (a human-milk based supplement).3. Lifestyle Adjustments & Surgeries: Gastric Bypass (weight reduction), smoking cessation, kidney transplant, hyperbaric oxygen therapy HBOT (large average effect, but no statistical significance)4. Diets: Vegan Diet, Green Mediterranean Diet, Mediterranean Diet, low fat and low carb diets.These interventions demonstrated a significant increase or acceleration of Biological Aging1. Pharmacological Interventions: Rapamycin (mTORC1 inhibitor, immunosuppressant), senolytics.2. Supplements: Buckwheat Extract 3. Gene Therapies: Follistatin (myostatin inhibition, muscle growth)4. Lifestyle Adjustments, procedures & Surgeries: Kidney DialysisThe findings are very reassuring regarding my health program and the Blueprint stack and some of the latest changes we introduced.Many of the reported findings echo my protocol and system, which is fascinating as it indicates that continuous measurement and optimization for actual biomarkers and performance indicators automatically consolidates the interventions that best slow down epigenetic biological age.Here are some examples:RapamycinIn September I stopped Rapamycin, based on concerns around its metabolic side-effects observed in my lab results (including increased cholesterol, blood sugar and RHR); the data here showed Rapamycin increased biological aging according to two clocks, while ineffective according to the others. Details here.MetforminI continue to take Metformin, despite concerns based on its ineffectiveness in ITP mouse studies (2), and claims about it blunting muscle growth (3) (I am top 0.1% of my age-group for muscle volume) evidence from this study and from aging clocks in non-human primates (4), as well as lowering cancer incidence in retrospective population studies (5), all indicate metformin as a promising longevity intervention.DietA green mediterranean diet fared best at reducing/slowing down aging as measured by 10 out of 16 aging clocks, this diet is the closest to my Blueprint diet. Also, I stick to a grain-free diet. The slight but significant acceleration in aging clocks observed with buckwheat extract further validates the choice of avoiding grains.Follistatin gene therapyThe study reported a significant increase in biological age with Follistatin gene therapy, primarily driven by its effect on the PACE aging clock. I have received this therapy, which successfully boosted my circulating Follistatin levels. Upon getting the gene therapy my PACE score dropped from 0.70 to 0.64. While this effect is associative, and is not necessarily caused or driven by the increase in my Follistatin, it is still reassuring that - at least in my case- Follistatin gene therapy had no undesired effect on my biological age. We remain very curious about the reported effect, and are investigating the potential underlying causes, and whether the analyzed Follistatin gene therapy was a healthy or a disease-specific cohort, which has a huge impact in interpreting this result.Minicircle, the company that provided my Follistatin gene therapy, had shared their data in a pre-print in which their Follistatin gene therapy did not associate with a change in PACE, however still showed that it mildly reduced Extrinsic Epigenetic Age, with a strong correlation to T and B immune cells.(6)Tracking my epigenetic biological ageI continuously trace my epigenetic biological age using the PACE (DunedinPACE) clock, as discussed this clock is superior in both reliability and sensitivity, especially in detecting shifts in biological age in healthy cohorts, all desirable features for a biological age clock.It's worth noting: as far as I know, I am the most epigenetic-measured person in the world. We saw its potential early on as an important way to measure biological age and inform our decision making. We remain bullish.Results validate some longevity interventions, but mostly indicate a wide gap in the systemic understanding of other interventions and the reliability of "single aging clock approaches" and animal data in assessing longevity outcomes in humans.Metformin has long been of interest as a longevity drug, and while some mouse studies including ITP failed to demonstrate conclusive lifespan extension with metformin, the picture here looks much brighter, with 5 out of the 16 clocks indicating significant reduction/deceleration in biological age, with no clock indicating the contrary. A recent study on monkeys also used multiple aging clocks to demonstrate the anti-aging effects of metformin (4), particularly in the brain, here's my post on this study.Anti-TNF therapies also reduced biological age across most clocks, indicating the significance of "inflammaging" in driving the aging process.On the other hand, Rapamycin, which is consistently the strongest drug intervention at extending lifespan in mice (solo and in combination with other interventions) according to several gold-standard ITP studies, surprisingly drives an increase in biological age according to 2 of the clocks, while having no effect on the remaining ones. This further puts to question the validity of rodent data in predicting longevity interventions in humans.As for the vitamin-B rich Buckwheat extract, B vitamins drive the methylation cycle, which drives up wide genome methylation as seen in this large elderly cohort study (7), potentially accelerating the aging-associated epigenetic changes. Furthermore, long-term B9 supplementation increased cancer incidence and all cause mortality, with the effect specifically correlated to the folate concentration in the blood (8).Evaluation of Aging Clocks' Reliability and Sensitivity Shows the Potential of the DunedinPACE ClockBeyond validating interventions, the authors also assessed the reliability and sensitivity of the 16 tested aging clocks by comparing them to one another and gauging how often a clock's result agreed/disagreed with the majority of the remaining clock, as well as how often a clock was unique in detecting a different for a particular intervention.DunedinPACE clock (a next generation clock measuring the speed of aging) stands out here by being always either in agreement with a majority of the remaining clocks, or uniquely detecting a change in biological age, where no other clock did.Sensitivity of Aging Clocks in Health and Disease InterventionsFor the longevity field, aging clocks that can detect changes in biological age in healthy people are of particular value. Improvements from treating a disease are usually greater in magnitude and easier to detect than incremental improvements from longevity interventions in healthy people.True longevity interventions should drive biological age reduction in healthy cohorts too, as they address the underlying aging process as opposed to particular diseases.Three clocks showed significant effect detection in studies on healthy cohorts, including DunedinPACE, while also being significant in disease studies. The GrimAge clock, geared for predicting mortality, also showed efficiency in both contexts.7 Organ-System Clocks, and Proxy Epigenetic Markets of Metabolites and Proteins are Reliable in Predicting Intervention Effects, including Diets.The latest generation of epigenetic aging clocks is called Gen X (for generation explainable), they aim to make biological age assessments more understandable by focusing on specific epigenetic signature that can link the effects on systemic biological aging to specific organs (called Organ system Clocks) and/or biomarkers (Called DNAm Proxies), in a manner similar to how conventional studies seek to elicit the mechanism of a drug or intervention.The example below demonstrates how these epigenetic clocks can predict the effects of various diets on organs, systems, and biomarkers, in other words the epigenetic data reliably recapitulates what we know about the effects of these diets on organs and biomarkers (e.g. vegan and mediterranean diets reducing inflammation, low carb diet reducing HB1ac)Closing thoughtsAging clocks are mostly a proxy (surrogate endpoint) for the actual endpoint of interest, which is lifespan itself (mortality data). Relying solely on mortality data would delay the field by several decades.Since aging clocks were not specifically designed to independently predict the effects of of various therapies or interventions on aging, their accuracy in determining the effect of a particular therapy on epigenetic age is yet to be fully established as they sometimes isolate particular negative effects, while neglecting positive effects that can still be beneficial to extending life-and health-spans.This lack of reliability and accuracy motivated the development of several generations of aging clocks algorithms, and the resulting lack of consistency in implementing the various aging clocks is what motivated this study to create a roadmap for the optimal use of aging clocks to evaluate anti-aging therapies and interventions.Be well,BryanSources1. https://biorxiv.org/content/10.1101/2024.10.22.619522v1.full.pdf2. https://pubmed.ncbi.nlm.nih.gov/27312235/3. https://pmc.ncbi.nlm.nih.gov/articles/PMC6826125/4. https://pubmed.ncbi.nlm.nih.gov/39270656/5. https://bmj.com/content/330/7503/1304.long6. https://minicircle.io/wp-content/uploads/2024/04/fstpreprint.pdf 7. https://jamanetwork.com/journals/jama/fullarticle/184898