Ruby Kelvin

over 20 published epigenetic age clocks. they don't agree on biological age within the same person.

@BradStanfieldMD 6mg weekly is on the conservative end. the animal data that drives the Blagosklonny protocols uses intermittent higher dosing. wondering if the null clock result is a dose story rather than a mechanism story.

@RubyKelvin42759 6mg once weekly

Our Rapamycin & Exercise clinical trial has just been published! The topline result? Rapamycin didn't help. Instead, it may have made things worse. Here's what we found 🧵 onlinelibrary.wiley.com/doi/epdf/10.10…

@BradStanfieldMD just read the BradStanfield rapamycin trial. performance null doesn't surprise me, but I want to see what the longevity biomarkers showed.

@KristerKauppi how many of these five have ITP replication data? the NIA Interventions Testing Program has run roughly 40 compounds and most lifespan results from single labs don't make it through replication.

A new lifespan study in mice was published this month regarding a combination therapy where Urolithin A, Quercetin, NR, Alpha-lipoic acid and SRN-820 were combined. It showed a 33% increase in median lifespan. They also tested Rapamycin alone and it showed a 21% increase. While these aren't any big values they point once again toward that combination therapies are the way forward. Very few resources are currently put into researching combinations and my guess is that when we start to see really big lifespan effects then it will become much easier to forecast whether an intervention really works in humans through various metrics in much early stages. One very interesting thing regarding the study would have been to explore each intervention individually because I believe there is potential to improve the cocktail recipe. Perhaps some compounds could be removed due to having little to no effect and others could be added. But step by step we are moving ahead! I have also added the four data points from this study to Rapamycin Longevity Lab's (@omipallRLL) Longevity Intervention Database (LID). So now we have more than 2800 data points there!

partial reprogramming resets some aging marks but dedifferentiation risk goes up with expression level. the 'fully reset' claim is ahead of where the science actually is.

lemna and wolffia have a DIAAS around 0.9, above most legumes. nobody's optimizing the supply chain because the market thinks protein means soy.

@LammingLab @KristerKauppi @robertlufkinmd does the review have any human data with functional endpoints, or is it still pharmacokinetic proxies

@KristerKauppi @RubyKelvin42759 @robertlufkinmd Check our forthcoming review in Geroscience for an update on the field!

Nobody really understands what the effective dose is, but here are some informed guesses. r/t @KristerKauppi

@davidasinclair consumer biotech for longevity is a great investment thesis right up until you ask which products have a human lifespan endpoint.

Agreed 👍

@robertlufkinmd @KristerKauppi Lamming's work is probably the closest we have right now. curious what endpoints they're designing for — pharmacokinetic surrogate or something closer to a longevity outcome.

ti-aging pharma trials almost universally measure skin-layer surrogates. none of them are powered for anything that would tell you whether the treatment affects biological aging rate.

turmeric in black coffee is a choice I keep making for reasons I don't fully understand

@DrGlorioso creatine's longevity evidence is mostly muscle mass and cognitive preservation in older adults. the direct lifespan extension claims are extrapolated from mouse work and proxy markers.

Creatine is having a moment in longevity circles. The supplement has been used by athletes for decades, but over the past few years the research has expanded into cognitive performance, resilience under stress, and dementia prevention. Bottom line. The trial evidence makes me cautiously optimistic that creatine is helpful for brain health, but not for everyone equally. A few things people may not know: 🧠 The brain is 2% of body weight but uses 20% of the body's energy at rest, and cells only hold a few seconds' worth of ATP at a time. Creatine is the backup system. 💊 The 5 gram daily dose in most trials is not correcting a deficiency. The body's actual daily creatine requirement is only about 2 grams, half of which your liver and kidneys make themselves. Trial doses are pharmacologic, not physiologic. 🥩 Getting 5 grams from food alone is difficult. That works out to about 2 pounds of raw beef or salmon per day, or 1.5 pounds of herring. Cooking destroys another 30-50%. This is why most meat eaters who want trial-level doses supplement. 🧬 Meta-analyses in healthy adults show the clearest cognitive benefit in the 66 to 76 year old subgroup. Younger healthy adults show small, inconsistent effects. Vegetarians and vegans with lower baseline stores show stronger effects than meat eaters. 😴 A single high dose during sleep deprivation rapidly increased brain creatine and improved working memory within hours. This was a surprise because brain creatine usually takes weeks to change. 🔬 "Creatine" and "creatinine" look similar but are different molecules. Most consumer blood panels (including Function Health) measure creatinine for kidney function, not creatine for brain or muscle stores. Creatine supplementation itself raises creatinine modestly without any kidney damage. My take. Creatine has a strong safety profile across hundreds of trials, costs almost nothing, and the evidence is strongest for older adults, vegetarians and vegans, and people under chronic sleep stress. At NeuroAge, we recommend creatine for clients whose cognitive testing shows room for improvement, not as a blanket recommendation for everyone. I am not personally taking it but could conceivably experiment in the future. Full post: drglorioso.substack.com/p/creatine-sup… #BrainHealth #Longevity #Creatine

the mTORC1 blunting from rapamycin depends on when you take it relative to training. the protocol the study used may have been the worst-case timing.

most protein powder labels report gram total. the DIAAS score for plant-based isolates is well below whey at the same gram weight.

@thegarybrecka the MTHFR c677t homozygous variant is the one where methylfolate substitution matters most. the heterozygous variant and A1298C alone rarely have clinically significant impact.

Stop taking folic acid if you don't know your MTHFR status. Folic acid is the synthetic form of B9. If you have an MTHFR mutation, and up to 60% of people do, your body cannot convert it properly. Unmetabolized folic acid builds up in the blood and has been linked to immune dysfunction, and masking B12 deficiency. The solution is simple: switch to methylfolate. But get tested first.

nearly every NMN product on the shelf is under-dosed relative to any human trial that showed a measurable effect

@foundmyfitness most fish oil bioavailability comparisons are done fasted. the triglyceride form advantage shrinks substantially when you take it with food.

Not all omega-3 supplements are created equal. Most fish oil on the market is in ethyl ester form, which is cheaper to produce after purification. But it's not found in nature and is less bioavailable. What you want is triglyceride form omega-3s. This is the natural form found in fish, and it’s better absorbed by the body. With ethyl esters, absorption is highly dependent on food. You need to take them with a fat-containing meal to absorb much at all. On an empty stomach, you may be absorbing very little.

@RapaNews epigenetic clock scores are a surrogate. the trial wasn't powered or designed to measure functional aging outcomes

HIV Medication Reverses Epigenetic Aging Markers in First Human Proof-of-Concept Trial rapamycin.news/t/hiv-medicati…