Leonard Pastrana

New study confirms what patients feel and we see in practice: aging accelerates in midlife. DNA methylation doesn’t drift linearly—it bends around age 40–60. That’s when even “healthy” patients show insulin resistance, body comp shifts, and lower recovery. Traditional medicine calls it “just getting older.” Longevity medicine knows it’s the turning point for proactive intervention. Midlife isn’t just middle age—it’s the bend in the curve. biorxiv.org/content/10.110…

🧬 Patients aren’t bouncing back like they used to. Even the fit ones. Even the young ones. Brain fog. Fatigue. Inflammation. Exercise intolerance. It’s not just “long COVID.” It’s spike protein-induced biological disruption—reshaping how we age. This changes everything. ⬇️ nubioage.com/resource/covid…

Your biggest fan is a stranger. Your biggest hater is someone you know. Noodle on that

Longevity medicine isn’t a new specialty. It’s how smart providers future-proof their care model.

@doctorinigo What devices do we have available to use in clinic to measure skeletal muscle adipose?

Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes. Conclusions: Increased intermuscular fat is associated with coronary microvascular dysfunction (CMD) and adverse cardiovascular outcomes independently of BMI and conventional risk factors. academic.oup.com/eurheartj/adva…

What really smart poor people cant handle is that getting rich has less to do with intellect and creativity and more to do with courage and perseverance. You gotta: Take risk others wont Work while others wait And keep going when others quit That’s about it. Oh - and wait 10yrs

@doctorinigo How can we as medical practitioners measure intramuscular fat? I have reached out to some companies that provide the device for clinical studies but no luck.

1/2 This study shows how intramuscular fat increases the risk of heart disease over subcutaneous fat. In our recent study we showed that sedentary healthy individuals possessed a significant decreased capacity to oxidize fat in muscle mitochondria compared to moderately active individuals (the control group). They also had a significant decrease in the activity of mitochondrial fatty acid transporters MCT1/MCT2, mainly MCT1. You can check the link to our study and some depiction in the post below. When individuals have a decreased capacity to oxidize fatty acids in mitochondria of skeletal muscle, intramuscular fatty acids accumulate outside skeletal muscle mitochondria. They are high in ceramides as well as in pro-inflammatory mediators which together are an important component in atherogenesis and therefore CVD. I have been hypothesizing about the conecction between skeletal muscle mitochondrial function and CVD for ~17 years and and very glad that scientific research is moving in this direction. -Skeletal muscle health and specially mitochondrial function are key to prevent diseases like T2D & CVD and increase longevity. #exerciseismedicine medicalnewstoday.com/articles/muscl…

Earn with your mind, not with your time. @naval

Phil Donahue died today at the age of 88. I never get tired of watching one of Milton Friedman’s greatest Donahue moments:

Why Resistance Training Alone Might Not Improve Your CVD Health! A new study reveals that relying solely on strength training without incorporating aerobic exercise may not reduce cardiovascular mortality risk. To truly protect your heart, cardio is essential alongside muscle-strengthening routines. Like, Retweet and Bookmark 🔖 7 Key Points From This New Study:- 1️⃣ Hypertension and PA Guidelines:- Hypertension is a major global health issue, and while combining aerobic activities and Muscle strengthening activities effectively manages blood pressure, their combined impact on mortality, particularly in hypertensive individuals, remains unclear. Current guidelines recommend at least 500 MET minutes per week of aerobic activity and muscle-strengthening activities on two or more days weekly to prevent disease and reduce mortality. 2️⃣ Global Adherence to PA Guidelines:- Despite these recommendations, over 80% of adults globally fail to meet both aerobic and Muscle strengthening activities guidelines, with most research focusing on the benefits of aerobic PA alone. 3️⃣ Study Demographics:- Study included 34,990 adults from the 2007 to 2013 Korea National Health and Nutrition Examination Survey, linking mortality follow-up data until 2019. 4️⃣ Result:- The study results shows, In hypertensive individuals, meeting aerobic PA guidelines alone reduced the risk of all-cause and CVD mortality by 24%, while meeting both PA guidelines lowered these risks by 40% and 43%, respectively. However, meeting only MSA guidelines had no significant impact on mortality. In those without hypertension, only meeting both PA guidelines reduced the risk of CVD mortality. 5️⃣ Stronger Effects in Hypertensive Individuals:- The protective effect of meeting aerobic and both PA guidelines, including Muscle strengthening activities, was stronger in individuals with hypertension. This supports findings that those with CVD gain more from PA, potentially due to improved endothelial function and greater blood pressure reduction, which may lower mortality risk. 6️⃣ Limitations of Muscle Strengthening Activities Only Approaches:- Meeting only Muscle strengthening activities guidelines may not provide significant health benefits, particularly for CVD mortality, as suggested by non-significant HR estimates. This indicates that without the recommended level of aerobic PA, Muscle strengthening activities alone might not be sufficient for reducing mortality risk. 7️⃣ Potential Explanations for the Risks of Exclusively Muscle Strengthening Activities:- The potential risks associated with Muscle strengthening activities alone, such as arterial stiffness and mild cardiac hypertrophy from high-volume resistance training, could explain the lack of significant differences in CVD mortality between those who meet only MSA guidelines and those who do not meet either guideline. Conclusion While this study highlights that aerobic exercise, in combination with muscle-strengthening activities (MSA), offers significant benefits for reducing cardiovascular mortality, it does not diminish the value of resistance training. Resistance training remains crucial for overall health and fitness. However, for comprehensive cardiovascular protection, it should be paired with aerobic exercise. Emphasizing both components in public health guidelines can provide a more balanced approach to improving heart health and reducing mortality risk.

@DanielJDrucker Doesn’t look like it did.

Might intranasal delivery of GLP-1 medicines provide a better therapeutic opportunity for neurodegenerative disorders #Alzheimers disease alzres.biomedcentral.com/articles/10.11…

@Andrea25633402 @DrAndyGalpin This study was done on genetically predicted vo2max.

@DrAndyGalpin VO2max Is associated with longevity but the association is not causal. A recent mendelian randomisation study found no effect on longevity.

Increasing your VO2 max is crucial because it enhances your body's ability to utilize oxygen efficiently, leading to improved endurance, better overall cardiovascular health, and enhanced performance in both daily activities and athletic endeavors. From a lifespan perspective, it dramatically reduces mortality risk and does not appear to have an upper limit - so the benefits do not taper off as you get more fit. The more, the better here.  With appropriate training, nutrition, sleep, and stress management, a 30-50% improvement in VO2 max is possible within 6-12 months, though the rate of increase slows as fitness improves.  Some published research even found that highly trained individuals can increase by 10-20% after a year, while untrained individuals might achieve this in 4-6 months. Please keep in mind how 'percent changes' work mathematically. Let me give you a real-life example of two middle-aged females whom I just started coaching last week. Client 1 is in moderately decent cardiovascular fitness, so I'd expect her to go from 33 ml/kg/min to 38 ml/kg/min in the next 6 months — which would be an increase of 5 ml/kg/min and represent 15%. That's a reasonable expectation and something I've personally seen in our clients countless times. However, client 2 is a former elite athlete and is still very fit. She's currently at 56 ml/kg/min, so increasing her by 15% would take her to 64 ml/kg/min. That's possible but not likely. Frankly, anything over 60 ml/kg/min would be an enormous jump. You can learn more about how and why to strengthen your heart and cardiovascular fitness, which is covered in Episode 1 of Perform with Dr. Andy Galpin.

@spinmonk @johngetstrong @Alan_Couzens @feelthebyrn1 @CalibreBio I found it to be very innacurate.

@johngetstrong @Alan_Couzens @feelthebyrn1 @CalibreBio Will do. Alan & Gordo have already shared some of their own experiences with it. Pros & cons (of course - it's not a met. cart). But on ⚖️ largely positive

Burning more fat at a higher power output is a sign of improved metabolic fitness In 2022, I was burning almost zero fat at a 5:30 min / km running pace. In 2023, I was burning 0.4g of fat per minute at a faster 5:00 min / km running pace. This is a good adaptation -- exactly the kind of change I was hoping for. Looking for the fat burning zone to shift further to the right and higher (more grams / minute) this year. That will be a sign of even better metabolic fitness.

Whitepill #14: Every day, two lists get longer: The things you believe but can't say, and the things you don't believe but must say.

@EricTopol @NatMetabolism Shocker

New evidence underscoring the importance of exercise, take note: "These results demonstrate that regular exercise during a diet-induced weight loss program has profound additional metabolic benefits in people with obesity and prediabetes." nature.com/articles/s4225… @NatMetabolism

@CharlesMBrenner @Longevity_Inv @CharlesMBrenner is it incorrect to say that SIRT1 is an NAD dependent deactlyase and that SIRT 1 deacytlates gene transcription factors like PGC-1a, PPAR, and Nf-Kb?

asked and answered: sirtuin critique published ✅ doi.org/10.1093/lifeme… lifespan book review accepted for publication (watch for it) ✅ @Longevity_Inv talk prepped for gstaad ✅ shana tov everyone (happy bday to the world)

15 Deep Philosophy Quotes of "Lao Tzu" | Thread

System‐level metabolic modeling facilitates unveiling metabolic signature in exceptional longevity onlinelibrary.wiley.com/doi/full/10.11…

Great disruptive article about new thinking around Alzheimer's. Several of us in the field of cellular metabolism have been quietly positing that AD is a metabolic disease due to disrupted cellular bioenergetics & mitochondrial dysfunction. Paradigm shift? bigthink.com/neuropsych/alz…

"The ideal life would be one where you had a hobby that as a byproduct made you money, you had a hobby that as a byproduct kept you healthy, you had a hobby that as a byproduct made you smarter and more creative." @naval