Fight Aging!

There are many different potential approaches to the treatment of aging as a medical condition. It is a sad truth, however, that funding the wrong type of project will almost certainly fail to move the needle on human aging. Further, it is almost certainly the case that most present effort in research and development is going towards the wrong type of project. A majority of the projects that could lead towards treatments for aging are focused on upregulation of the cellular stress response mechanisms triggered by exercise, calorie restriction, hypoxia, heat, and the like. We have a good idea as to the likely outcome of such approaches in humans: look at the results of structured exercise programs and calorie restriction, meaning a modest slowing of health that does little to change the present shape of a human life, and its decline into disability and mortality.

A different approach is needed if the goal is rejuvenation rather than a gentle slowing of the aging process. That approach should be to repair the various well-described accumulations of cell and tissue data that lie at (or close to) the root of aging, thereby allowing restored function. Clearance of senescent cells from aged tissues is an important example of this type of approach. Senescent cells secrete signals that provoke chronic inflammation and tissue dysfunction: their presence actively maintains a more aged, damaged state of organs. Targeted removal of even only a third of such errant cells produces quite startling demonstrations of rejuvenation in mice, reversals of age-related conditions that are greater and more rapid than can be obtained by even the best of stress response upregulation approaches (such as mTOR inhibition). And yet there is a great deal more of work analogous to mTOR inhibition taking place than work analogous to selective destruction of senescent cells.

Aubrey de Grey on Rejuvenation Policy at EARD2021

If we look at the maintenance approach, the damage repair approach, that, of course, I founded more than 20 years ago now, that has become very much the focus or one of the major focuses of the anti-aging research field. We can see that potentially, there is a bit of an issue, because there are lots of different types of damage that we have to go after.

Of course, the whole reason why geriatric medicine was originally seen to be a non-starter that would never really have all that much effect on the healthspan of the human race was because of that precise problem that there are so many things you have to fix. The maintenance approach kind of sidesteps that; it makes the divide-and-conquer problem more manageable in ways that I've talked about many times and I won't reiterate now.

But still, it's a divide-and-conquer problem. And that means that we have to make quite sure that the most difficult parts of that divide and conquer approach are not left behind and neglected. Of course, SENS Research Foundation was set up more than a decade ago, with exactly that in mind; we set it up as an independent charity, an independent nonprofit funded almost entirely by philanthropy.

We did that precisely in order to avoid the constraints that forced both industry and mainstream academia into short-termism into focusing on low-hanging fruit and neglecting the harder but equally important problems that otherwise they might work on. Of course, the past decade of work that we and others have done, has had great successes, and certainly some of those successes constitute progress in the most difficult areas of damage repair.

For example, in the area of mitochondrial mutations, in the area of extracellular matrix stiffening, these are areas which were completely stalled when we started, and they're not stalled anymore. But they're still nowhere near as far along as getting into clinical trials, for example. So we've got to make absolutely sure that that does not persist, that these things are continuing to be pushed forward.

That's where emerging challenge number one is: it is extraordinarily hard to get most people to not focus on the low-hanging fruit. In industry, of course, we know that people who want to make money, they want to make it soon, and therefore they are going to put pressure on to cause that to happen. Some of you who have long memories may recall a company called Elixir Pharmaceuticals, which were founded by two absolute demigods of gerontology, Cynthia Kenyon and Leonard Guarente. The reason why those of you with short memories will probably not remember Elixir is because it ended up being a complete waste of time. That was why: they took the wrong money, they got pressured into doing stuff that wasn't useful, and nobody remembers them at all.

It's, of course, exactly the same in academia, that short-termism arises from the need to publish or perish. And same result. The worst of it is that it's quite easy in biology in general, and certainly in our field, to identify areas where you can make quick progress and make a big splash and get a terribly interesting paper on the front page of Science Magazine. Unfortunately, it doesn't go anywhere, because there is no actual way to take it forward to something that would have clinical relevance in the long run.

And the final problem, a final aspect of this problem, is that most of the real visionaries who have money are actually capitalists: they are people who made their money in the private sector, and they believe in that kind of way of doing things. Many of them simply do not believe in philanthropy, or in charity in general.

Now, some of those people have been visionary enough to recognize that they have to bite that bullet. Of course, the person who gets the greatest credit for that in our world is Peter Thieltps://en.wikipedia.org/wiki/Peter_Thiel">Peter Thiel, who started funding Methuselah Foundation back in 2006. But the fact is now that these people have the opportunity to invest rather than to donate, they are very, very tempted to do exactly that. So we absolutely need to be vigilant in making sure that the most difficult components of the damage repair portfolio are not neglected.