Success in Rejuvenation Research to Date is Partial: Many Projects Still Need Our Philanthropic Support to Flourish

The past few years have seen very encouraging progress in rejuvenation research and the commercial development of therapies. Senolytic treatments capable of clearing senescent cells, one of the root causes of aging, are moving towards human trials, with a number of companies hard at work on therapies at various stages of development. The animal data continues to roll in, and continues to look very promising, with senescent cells shown to contribute directly to an increasing number of age-related conditions. In addition the established mainstream efforts to remove age-related protein aggregates such as amyloid-β, tau, and α-synuclein are broadening the number of targets and strategies, and in addition are coming closer to success after many years of failed trials. Amyloid-β has finally been cleared from human brains in a clinical trial, and many of the newer approaches to reducing levels of various forms of aggregate seem quite promising in animal and human studies. These aggregates are another of the causes of aging and age-related disease, there is a real sense that the present time is a tipping point in this area of medical development.

As you've no doubt noticed, this zeitgeist has been reflected here at Fight Aging! in an increased consideration of startup companies and the early steps in translation of the most important lines of research from laboratory to clinic. Similarly, groups like the SENS Research Foundation and Methuselah Foundation have also focused a sizable fraction of their attention on this part of the development process. See, for example, the Rejuvenation Biotechnology conference series of the past few years that brought together academia and industry, and the Methuselah Fund launched this year.

Yet it is important to remember that all of this welcome progress, the move from non-profit research to for-profit development, with human trials on the near horizon, is only taking place for a fraction of the areas of science and technology required for comprehensive human rejuvenation. Yes, senescent cell clearance is well under way now, and both protein aggregate clearance and cell therapies seem well funded and pointed in roughly the right direction. But what about therapies to address glucosepane cross-links, a cause of blood vessel stiffening and bone fragility; or the mitochondrial DNA damage and consequent mitochondrial malfunctions that are implicated in such a wide range of age-related disease; or the scores of other forms of metabolic waste found in lipofuscin and amyloids? What about the decline and disarray of the immune system; what about steering the cancer research community towards universal therapies based on prevention of telomere lengthening, applicable to all cancers?

Aging has multiple root causes. Fixing one root cause - say if senescent cell clearance progresses stupendously well, and we're all having 75% of our senescent cells removed at a $15,000 price tag for a form of FOXO4-p53 interdiction via medical tourism sometime around 2021 - has a limited upside because it is only one root cause. Each of the categories of damage outlined in the SENS view of aging is ultimately fatal in and of itself, though it is far from clear which are more or less important to any specific aspect of aging. Remove just one and some forms of mortality will decrease considerably. Others might be postponed. Yet more might be only slightly affected, however, and they will still kill you. The upside of partial rejuvenation is nonetheless a much better prospect than anything that can be done with yesterday's medical technology, but it is only the opening chapter, not the whole story.

Yes, we should do what we can to help commercial development: invest if we are able, cheerlead and publicize if we can. But we can't become distracted from the important lines of research still underway in their earlier phases, prior to the point at which they can make the leap to startup companies, and in need of philanthropic support to move ahead. Despite the considerable evidence supporting the SENS view of aging as damage and rejuvenation as damage repair, the research community and institutional funding sources continue to give little attention to lines of work that are capable of becoming just as large and just as important as senolytic treatments to remove senescent cells. Prior to 2011, senescent cell clearance was another of those ignored lines of work: that success can and must be repeated for the others.

Of the less well supported lines of work that could turn back aging, those closest to realization appear to be: immune system restoration via some form of targeted cell killing; immune system restoration via regeneration of the thymus; pharmaceutical clearance of glucosepane cross-links; and allotopic expression of mitochondrial genes. These are all still at the stage wherein the charitable donations that we as a community can raise for specific projects, or provide to the SENS Research Foundation, make a real difference. These projects all appear to me to be a few years from reaching viability for commercial development, on average, and they all scrabble for needed funding to one degree or another. All of these should produce similar overall degrees of benefit to those produced by senolytic therapies, albeit in very different ways. This is where we can accelerate progress towards the near future of greater human longevity, just as we have in the past.

Growing success in portions of the broader field of rejuvenation research should encourage us: it shows that the support we have provided over the last decade or more has worked. Things are moving, the wheel turns. We can do the same for the parts of the field that have yet to attract the attention they need, have yet to reach the same level of enthusiasm and funding. Give it some thought.


Speaking of thymus regeneration and senolytics, Bill Faloon recently started a website for patient-organized clinical trials:
Senolytics are on his list, thymus regeneration, stem cells and some others. The goal seems to circumvent medical regulations for the adventurous and create some useful data on the way. Since he's experienced with the FDA I guess he checked the legal issues beforehand.

Posted by: Matthias F at August 28th, 2017 10:44 PM

@Matthias - USD 28,000 to get on the thymus regeneration trial! Do they mention what approach they are taking anywhere?

IMO this could generate a lot of negative PR. I wish they'd instead take the approach proposed by Alexander Masters:

" "The biggest complaint about your scheme is going to be that it means rich people are getting treatment and poor people aren't. But you've dealt with that by ensuring benefits go to people who can't afford the treatment."

This is, in fact, critical to the scheme. An early-phase clinical trial might involve 15 or 20 people; so, to set up a personal trial, the wealthy donor also has to pay for 14 to 19 poorer patients. There is no way round that. The donor is shackled to beneficence. Savulescu believes this necessary generosity is vital to funding medical care in the future. "People don't understand that there's an extraordinarily limited health budget. People are denied access to interventions and treatments all the time because it's too expensive to provide them. You could find cures for these rare forms of cancer very quickly if you put enough money in, given the huge advances of science, but it's too expensive, and if you rely on conventional funding modes it is just not going to happen. I had a similar idea to yours: there's this new form of cancer therapy called proton therapy. It's very expensive and delivers very high doses in a very precise way with much less tissue damage than other treatments. My idea was, why don't you build a state-of-the-art facility and have half of the patients massively rich oil billionaires from the Middle East?" "

It is actually a much trickier problem than appears:

" O'Connor's next objection had not occurred to me at all: "What happens if the drug works?"

"Splendid. He's bought back his life and the lives of 20 others, for a measly £2 million."

"And he's going to want to go on having access to the drug. Very few trials are for a drug that might cure you outright. Most are to treat chronic conditions, like cancer or diabetes or HIV."

"Of course."

"But then he'll have to provide it for all the other patients who'd been on the trial too, otherwise they'll die."

In short, the wealthy individual gives £2 million, returns home triumphant from the hospital, and finds a bill for another £10 million lying on his doormat because he's now got to fund the drug in perpetuity for every other patient who shared in the risk of the trial in order to let him have access to it. In fact, as O'Connor pointed out, it would not be a lifelong commitment because there is well-established etiquette on this matter. A lot of drug companies say, "If you're on this trial and it works, we will pay for you to have the drug for the next two years." Within these two years other sources of funds will have been easy to find, because everybody loves a drug that works.

But then, added O'Connor, there's the adjusted problem: what happens if the drug works for some of the people on the trial, but not for the donor? He still finds a £10 million bill on his doormat, only this time he's come home knowing he's about to die. "I suppose that's just the risk of doing business in this way," said O'Connor, answering his own question with unexpected corporate brutality - the brutality of the ethicist rather than the moralist."

Posted by: Jim at August 28th, 2017 11:59 PM

new project that need our support at lifespan dot io. i have already donated.

Posted by: Norse at August 29th, 2017 4:39 AM

Every quarter I throw a few bucks at Aubrey, and I think most of us do that from time to time.

That being said, some of these companies that are in early stages (Think Ichor, Oisin etc) will probably go public at some point. Investing in these companies is a triple win.

1) Help move the product development along of the therapy (And hopefully make a few bucks along the way)
2) Continued awareness of the technology to the moneyed class
3) The SENS family of companies intend to help move the other technologies along once they are established.

Jim Mellon's book should be out in a month. I've reserved a copy. That book is going to tell us a great deal about where the first wave of funds are going to be distributed. From there, we should follow Aubrey's lead and see what areas are lacking and do our best to fund and push focus in that direction (Divide and conquer).

I have a good feeling about glucosepane breakers. That is an area ripe for the taking. The other areas I don't know as much about and have to do some reading.

Posted by: Mark Borbely at August 29th, 2017 9:54 AM

I don't have any more information than what's on the website, but I thought I'd share it anyway, because it's quite interesting if that scheme works.
But I don't think the ethics shown in that theoretical example work here. First the numbers don't fit and a thymus regeneration isn't applied frequently. But even if it was - suppose we have a wealthy donor that pays for the trial and doesn't help the other patients on the trial any further. So they die. But they would have died anyway and got a bit more time. And the lifes of numerous others that come later can be safed.
So that selfish rich donor still does more good than someone that tries to stop him on ethical grounds.

Posted by: Matthias F at August 29th, 2017 12:10 PM

@Mark Borbely: Every month I throw some buck at AdG.

Posted by: Norse at August 29th, 2017 12:31 PM
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