João Pedro de Magalhães on Rejuvenation Therapies

Here find an interview with researcher João Pedro de Magalhães, nowadays involved with a new cellular reprogramming company as well as ongoing research programs in the UK. One of the more interesting parts is the commentary on rejuvenation versus slowing aging, noted below. I agree that terminology, definition, and measurement are challenges at the moment. But I would say that he is overly conservative on the point of whether or not rejuvenation can be produced in mammals, given the extensive evidence for senolytic therapies to reverse aspects of aging and the progression of specific age-related diseases.

You could argue that there are some really simple model systems where we can reverse aging. You could also argue that we can reverse aging in human cells with telomerase and cellular reprogramming with Yamanaka factors, but whether that applies to whole organs is a completely different question. The jury is still out on whether we can actually reverse aging in mammals.

I think this might be a terminology issue. If you take an obese individual, and this individual goes on a diet, they will be healthier. Their risks from various age-related diseases are going to decrease because of the diet, but that doesn't mean that this person has been rejuvenated, it just means that a lifestyle intervention improved their health.

A lot of times, you can have interventions that improve health and maybe ameliorate elements of epigenetic clocks without necessarily doing anything about the process of aging. I think we've had this problem in the field for quite a long time - that you can have interventions that increase longevity without necessarily retarding aging, just because they're healthy. Do obese individuals age faster? I wouldn't readily assume so, although some of my colleagues may disagree with me.

You can have interventions, pharmacological interventions, for instance, that extend lifespan, but don't slow down aging in humans and even in model systems. Mice mostly die of cancer, and if you have a drug that prevents cancer, the mice are going to live longer. It doesn't mean aging has been retarded, even though longevity has increased. The problem we have in the field is what do those various interventions mean? Do they really slow aging, do they reverse aging, or are they just healthy? That's why we sometimes need to be more careful about what we are claiming to have achieved.

How would you show something like aging reversal? To me, there's still a question mark on it. I think you must have some pretty strong evidence for it - functional evidence, molecular evidence. It has to be something quite substantial to prove that you've reversed aging in a mammalian organism, that you've rejuvenated a tissue. I think that would require some pretty substantial evidence which I haven't seen yet. Going back to the question, in complex models, such as mammals - no, I don't think we have really reversed aging.



Speaking of senolytics....

Any chance, Reason, you'd want to do a blog entry on the current status of senolytic therapies at the moment? The only clinical trial "going on" right now that I can easily find is this one:
and they are supposedly "still recruiting"!?

I could use a morale boost

Posted by: GREGORY S SCHULTE at May 19th, 2022 11:55 AM

He may say he is conservative, but he is one of the researchers out there that believes in radical life extension & he is working on cellular reprogramming.

Gladyshev spoke on the Sheekey Science Show on Youtube recently about his lab's work. He said that they would like to research more closely what is happening during embryogenesis. Is it OSKM? He said we don't really know.

Posted by: Matt at May 19th, 2022 12:52 PM

Hasn't Harold Katcher already demonstrated that age is in fact reversible in mammals?

DNAm aged reversed- check
Memory improved- check
Problem solving improved- check
grip strength improved- check
body composition improved- check
more youthful blood biomarkers- check

Posted by: Lee at May 19th, 2022 3:25 PM

First time I hear of this guy and I'm Portuguese...

Posted by: mcmp at May 19th, 2022 3:44 PM

@GREGORY S SCHULTE: Going by the info at, there are three senolytic compounds in clinical trials and seven more at the preclinical stage. There may be more - whether any of them has a fighting chance to make a difference is a different matter.

Posted by: Barbara T. at May 19th, 2022 4:03 PM

@Lee: yeah, whatever happened to Katcher's magic Elixir? His rats experiments never seem to be moving on to randomised controlled clinical trials...

Posted by: Barbara T. at May 19th, 2022 4:08 PM

@Barbara i don't have any new information except to point you to Josh Mittledorf's blog where Harold and his business partner Ashkay comment fairly regularly. I think dog trials were/are scheduled at Greg Fahy's lab at some point.

Posted by: Lee at May 20th, 2022 10:00 PM


Posted by: KATYUSHA at May 24th, 2022 2:59 PM
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