George Church Discusses Gene Therapies as a Basis for Therapies to Control Aging

George Church is one of the more noteworthy business-oriented scientists whose work touches on aging and longevity science. He is involved in a number of different companies, and while his primary focus is genetics, his interests include tissue engineering, farming engineered pigs for xenotransplantation, and a range of other items. Just about everyone of note in the scientific community has a different view on aging: the theory, the plausibility of various endeavors, and how best to go about tackling it as a medical challenge. This interview illuminates a little more of Church's viewpoint, which is, as one might expect, quite focused on using gene therapies as the primary tool for delivery of therapeutic effects. In principle, though not yet in reality, a gene therapy can do everything a drug can, more effectively and more accurately. There is a little way to go yet in generating the necessary methodologies and a reliable technology platform, probably built atop CRISPR.

Is there an accepted causal or ultimate theory of aging? There are hypotheses and different schools of thought. It's not so mature that there's total consensus. There are relatively few exciting fields of biology where there's total consensus. In aging, there's a school of thought that it's all about damage and you have to repair that damage. There's another school it's all about regulation and epigenetics, and if you get the cell in the right epigenetic state then it can repair its own damage; a young cell is much more powerful at repair than an old cell.

Then there's hallmarks of aging - about nine components - and maybe you have to get all of them pushed back for rejuvenation. I like this version where they talk about specific biological mechanisms. If you fight or leverage those mechanisms you get your best shot at treating aging. Why we age is less useful than the mechanisms, but having some intuition for why the mechanisms are the way they are can help you manipulate them. And very often you want to manipulate them in an unnatural way, and that requires a deeper understanding. If you're trying to do something totally natural your protocol is clear. If you find that in the western world we're eating a lot of marbled cow that didn't exist in the ancient days, all you have to do is get rid of the marbled cow and you're all set. On the other hand if you're trying to get people to live past 150, there's no precedent for that.

Certainly if you could fix all nine hallmarks at once that would do well to solve aging. Reversal of aging has been demonstrated in simple animals. Some people will dismiss those as too simple - because they have such a short life already, it's not surprising you can make them live longer. But I think it's quite clear that aging is programmed in some sense. It's not like you've been programmed to die at some age, but the laziness of evolution has resulted in your program to not avoid dying. Over evolutionary time, to use analogy, it was not cost effective to invest a lot of your precious food to live longer because you're going to get eaten by a wolf anyway.

To address the hallmarks of aging, the idea is to take the subset of genes that has been demonstrated to work for longevity or aging reversal in smaller organisms and reconfigure them into something that's usable in gene therapy. You change it from longevity that requires introducing it into the germ line, which is not really a good strategy for humans because most of us that want longevity are already past the zygote stage, and we're reconfiguring it as a adeno-associated virus gene therapy.

How far off is age reversal? The simple answer is, I don't know. Probably we'll see the first dog trials in the next year or two. If that works, human trials are another two years away, and eight years before they're done. Once you get a few going and succeeding it's a positive feedback loop. The FDA doesn't need to classify aging as a disease in order to treat it. If you actually have something that causes aging reversal, they'll approve it. You'll frame it in conventional terms, but it can have additional benefits. In other words If you have something that fixes one disease problem and happens to fix a bunch of others, you don't need to put them all on the label. The FDA doesn't stop you for using things off label or curing two things at once.



Great to see him in favor of Hallmarks of Aging, that means a lot of what he wants to do will overlap with SENS which is good news.

Posted by: Steve Hill at December 4th, 2017 8:04 AM

@Steve Hill: He's on the SENS Research Foundation's advisory board.

Posted by: Reason at December 4th, 2017 8:20 AM

A good read. The phase Hallmarks of Aging seems intentionally fuzzy. A label like Proteostasis dysfunction is not useful in organizing treatments.

Posted by: JohnD at December 4th, 2017 12:00 PM

@JohnD , yeah, Hallmarks are clanky, mixing things from various levels. For example they count loss of stem sells and shortening of telomeres -- while first is mere the reason for second. Hovewer, they are better than nothing in a world where pure SENS model is not very popular.

Posted by: Ariel at December 4th, 2017 12:13 PM

Are you sure Ariel? Stem Cells lose telomeres too...

Posted by: Mark at December 5th, 2017 2:54 AM

Its basically the same thing as aubrey has said many times. Church is on the leaf advisory board too reason its just good to hear he likes repair approaches.

Posted by: Steve Hill at December 5th, 2017 5:24 AM

"Probably we'll see the first dog trials in the next year or two. If that works, human trials are another two years away, and eight years before they're done."

Does he mean 8 years from now or 8 years from the start of the human trials? Either way it's quite a long time but i applaud his effort.

Posted by: Fuzzymath at December 12th, 2017 5:47 AM

Also he refers to 9 different hallmarks. Is it accurate to say he disagrees with Aubrey about the number of "7 deadly sins" ?

Posted by: Fuzzymath at December 12th, 2017 5:51 AM

Also he refers to 9 hallmarks. Is he in disagreement with Aubrey about the number of "7 deadly sins" ?

Posted by: Fuzzymath at December 12th, 2017 5:52 AM

@Fuzzymath: The Hallmarks of Aging is a model of aging analogous to SENS but prioritizing different potential causes of aging. There is some overlap, but from the SENS point of view, the Hallmarks includes things that are not primary causes, but rather secondary effects.

Posted by: Reason at December 12th, 2017 7:32 AM
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