Pharmacologic inhibition of mTOR with rapamycin or its analogs shows promise for lifespan and healthspan improvement, even when initiated late in life.

“Mice that are given a drug called rapamycin, which is used to suppress the immune system in patients, but you can take low doses as a human, or give it in low doses to a mouse. Those mice live dramatically longer, even if you give them rapamycin when they're 20 months of age, which is a really old mouse, that'd be like a 75-year-old human, they still live longer.”

“we could with enough capital week and money invested we could do multiple different experiments we could do people in their 50s 60s 70s and 80s so let you know dream with me the other thing that makes me optimistic is it's not just recognizing that works late in life we've got results in my lab now that we'll be publishing that if we start even later than 600 days in a mouse which is what close it to 70% yeah we can still extend lifespan”

“the curves for the early start nine months or late start 20 months we're compared very carefully by scott pletcher who's a mathematical demographer biodemographer and they're indistinguishable that is there's no statistical difference between the early start mice and the late start mice”

“the gold standard intervention for treating mice which is caloric restriction typically only works when initiated earlier in life and so typically when you wait until a mouse is two years old to begin calorically restricting it it's too little too late”

“our study where we did three months right of rapamycin treatment between 20 and 23 months of age and then let them go to the end of life the magnitude of effect was pretty similar to what the itp saw so it was it was reasonably close to continuing um treatment”

“you know what has emerged now is there are five or six or seven or maybe even more different interventions that can be initiated in middle age or even in late age in mice and you actually go it's not only that you slow down the declines you actually reverse the declines”

“it was really the first time anybody had convincingly shown that you could start an intervention intervention not even and get robust lifespan extension and for me honestly i reviewed that paper and when i when i first time i saw that result i'm like this changes everything we actually have a chance for translational geroscience because because you might be able to intervene late in the aging process and have significant impacts so it honestly in in that was 2009 paper came out so in the 13 years since then the whole paradigm in the shields field has changed right most people who are studying interventions today are studying things that they test for efficacy late in life because that's what we need to do in people”

“and what they found was that they got this robust lifespan extension from starting with rapamycin treatment at 20 months of age and just to give some context that's about the mouse equivalent of a 60 or 65 year old person”

“so with rapamycin you get almost exactly the same benefit starting at 20 22 24 months as you do starting early in life so that might tell us that there's a difference right there clearly there's a different mechanism potentially as well it could be that rapture is doing something different or it's a different dose effect exactly so so that that's an open question exactly why it's different but it seems to be it seems to be different”

“I still think we are really in early days of understanding what pharmacologic inhibition of mtor can do again there's really a lot of promise with this approach in virtually every other model species outside of humans and that doesn't mean it will work in humans but it's very interesting and I think if we had better biomarkers which again I think that's something that can happen in our lifetime I I think that's a very promising strategy and it's especially promising when you consider that the animal models show that M pharmacologic inhibition of mtor using rapamycin or its analogs even applied late in life still provided lifespan and health span Improvement”

“it's not counterintuitive to me that exercise or calorie restriction induce a longer life in the right model it's a little counterintuitive to me that rap ay does to be completely honest like I I don't dispute it for a moment because I've seen it now over and over and over again but it's still remarkable to me that a molecule is able to act at a fundamental level of Aging”

“rap ofy in that first paper was also the first drug I believe where anyone had showed we we found that it works quite well even if you start in really old mice some of the mice that were exposed in that paper did start until 20 months of age where the median survival is about 24 for males and 26 for females it took me very much by surprise”

“when you compare within sex so you're comparing older females to younger females there's no difference surprisingly the benefits you get starting in old age and the benefit you get starting in young mice is statistically insignificant in females and it's statistically insignificant in males in both sexes starting as is 20 months of age does not diminish the um ability of the drug to extend lifespan”

“fast forward to 2009 and um a very welldone study is published as part of the interventions testing program that looks at the use of Ramy in a very well documented strain of mice that are far more representative of what happens in biology than the typical strain of mice that are used in a clinical research setting you know the rest is history basically that study showed more convincingly than any other study in the ITP history that Rapa extended life in male mice in female mice and most importantly when initiated very late in life a period of time in which No Other Drug had ever been able to extend life”