Rapamycin Longevity Lab

Wanna know what I am so tired of? I am so tired of armchair science commentators and influencers posting uninformed and misleading comments about longevity science. I understand the knee-jerk reaction, because there are plenty of irresponsible and sometimes dishonest people promoting sirtuin activators (or fake sirtuin activators such as resveratrol) as proven longevity therapies. Rapamycin less so, although the hype can definitely get ahead of the data at times. As someone who has been working in this space on both sirtuins and rapamycin for nearly 30 years - in fact I co-authored both the first sirtuin longevity paper and the first rapamycin longevity paper - I know something about this topic. Rapamycin is definitely not a "dead end". In fact, it's about as far from a scientific dead end as you can possibly get at this point. Sirtuins are harder to quantify, but it seems premature to characterize the entire family of proteins as a "dead end" for longevity at this point. Sirtuins have many important biological functions; that's clear. They do not appear to be central regulators of longevity in mammals, but they do intersect with the longevity network in interesting ways. SIRT6 might indeed be a legitimate target for slowing aspects of biological aging, although the body of literature here is limited and comes from only a few labs. However, the fact that there is both mouse data and human genetic data for SIRT6, suggests perhaps we should not completely ignore this protein as a potential target for longevity. In my opinion, it is extremely unfortunate that people have started selling putative "SIRT6 activator" supplements, but that follows the long tradition in the sirtuin space of letting marketing get way out in front of legitimate science. Rapamycin, on the other hand, is by far the most robust and reproducible drug for increasing lifespan and slowing age-related decline in laboratory organisms spanning more than one billion years of evolution. This is backed up by multiple genetic lines of evidence using loss of function and gain of function variants in the mTOR pathway, and has been replicated by dozens of labs across hundreds of studies. It is about as rock-solid as things ever get in biology. There is also unpublished (but presented at conferences) data that rapamycin can increase lifespan in non-human primates. What about mTOR and rapamycin in the real world? There is human genetic data also supporting the idea that mTOR signaling is associated with longevity in people. There is early randomized clinical trial data in companion dogs suggesting that rapamycin can improve age-related declines in heart function, activity, and quality of life. There is a growing body of data across numerous independent studies that rapamycin may improve immune aging, brain aging, ovarian aging, age-related changes in body composition, and a variety of chronic inflammatory conditions in humans. It's true that most, but not all, of these studies are small and underpowered for strong conclusions. Fortunately, a couple of major initiatives, including the ARPA-H PROSPR and the R. Ken Coit-funded clinical trial at U. Arizona, will generate larger clinical trial data sets for rapamycin in older adults in the coming years. This information is all in the published literature for anyone who wants to put in the effort to become informed. I'll also be speaking on this topic at @LongevityDublin next week. The title of my talk is "Is Rapamycin Dead?". You can probably guess the answer. Once I get back, I will put together a video for @longevityscipod . You might want to check it out.