Fight Aging!

George Church is a noted geneticist, involved in a number of gene therapy projects that relate to aging in some way - though largely through manipulation of metabolism to slow aging rather than by directly attacking the root causes of aging. Gene therapy tends to lend itself to adjustment of cellular metabolism first and foremost, raising or lowering expression of regulatory proteins, but there are certainly ways in which it can be used to produce repair of damage rather than changes in cell behavior to override reactions to that damage. Church is clearly one of those who thinks that the viable path for aging is to produce incremental gains via adjustment of metabolism to look more like that of very long-lived species. This is more or less the polar opposite of the SENS view on the road to human rejuvenation via repair of the underlying cell and tissue damage that causes aging.

Do we have any successes with gene therapy specifically in the rejuvenation field?

That's a little further out. I mean, most are in pre-clinical animal trials or in very tiny, not yet approved human trials. But yes, pre-clinical animal trials are looking good. We published two papers, one on three genes that spread from the site to which they were delivered systemically, and another one about three genes that are localized; these are the so-called Yamanaka factors that cause rejuvenation. Those are two different studies.

Therapies for animals is something that one of your many start-ups, Rejuvenate Bio has been doing. Recently, it has secured another 10 million in funding, and it has been alive for a few years, so what is the situation there?

Rejuvenate Bio was involved in both of those papers, and those were both in mice, and they since have taken one of those two combination gene therapies, three different genes, things like fibroblast growth factor (FGF21), the soluble form of the TGFß receptor, and aKlotho. Anyway, that three-gene combination has then been moved into dog trials. So, this is not an animal model, this is an actual veterinary product, because people do care quite a bit about their pets.

Do you think an abundance of private initiative is the way to go when it comes to fighting aging, or maybe governments should play a greater role?

I think, and some of my colleagues agree, that we need to re-educate the FDA to be more interested in preventative medicine and in aging as a disease, and I think that's a fine goal, but that could take time, and that's uncertain. I think it's easier and probably better to just accept that something that works on the core, fundamental components of aging will also reverse several different types of diseases simultaneously. We are working on eight different diseases. In a way, diseases of aging are even better than biomarkers, because they are really what we care about. That doesn't require the FDA to think revolutionary new thoughts or wrap their heads around something strange. It also has advantages over preventative medicine. I love preventative medicine, we work on it, but to convince a cautious federal agency to give a dose of something powerful to someone who is already healthy...

So, most preventative medicine has been very benign, a very "do no harm" sort of thing. But in this case, if you work on eight different diseases of aging, and some of them have a fairly early onset, and you can actually show reversal, you will get approval. Then you will have, as a side benefit, preventing all the other diseases. You will not only cure the early-onset disease, you will prevent all the others. That is, if you have the right thing.

Do we even know how to aim at life extension?

I don't think we do. I think if we get serious aging reversal, it's something that we can continue to improve on, just like we improved on transportation from the first wheel to rocket ships, or the way we moved from being able to sequence a few base pairs of DNA to being able to sequence the entire biosphere. The thing is to get the foot in the door where we're actually working on the core processes of aging, on the clock that decides that a mouse is going to die in two years and bowhead whales die in two hundred. If we get to that core thing, then we can keep improving it, and, if you keep reversing, there is a chance that you can do that for a very long time. But I don't think this should be the goal. It's hard to do clinical trials on that. The trial where you show that you've extended life by even fifty years would be a very expensive, very long clinical trial. So, let's just focus on things we can do in weeks.

Link: https://www.lifespan.io/news/george-church-on-gene-therapies-and-longevity/