The Daily Mail interviews Andrew Steele, the author of Ageless: The New Science of Getting Older Without Getting Old. Steele makes a couple of key predictions in the interview:
"I'd be shocked if in five years we don't have some senolytics in the clinic. It probably won't be for aging at first. It'll be for a specific disease - and maybe in 10 years, we'll use it for aging. These things are very, very near term."
This market is conerned with the second of those predictions: Clinical use of senolytics in humans for the specific purpose of slowing, reversing, or preventing aging by 2033 (within 10 years of 2023). Senolytics are simply drugs whose mechanism of action is the destruction of senescent cells.
Resolves YES if credible news articles or medical journals describe the successful clinical use of a new senolytic drug for anti-aging purposes outside of trials before the end date. Resolves NO otherwise. I will not be betting in this market.
1,000
3.00I think Aubrey de Grey has an interesting view on aging; it's accumulation of damage from the wear and tear of metabolism/living, and so rather than trying to prevent it by manipulate the complicated metabolism its better to repair the damages in a continuous way before they get overwhelming. Now, I'm not sure if this is what senolytic drugs do? They destroy senescent cells, which means "cells that permanently stopped dividing" so I guess it counts as repair to remove them? Maybe, I remember that de Grey classifies a bunch of different classes of "repair". In either case, here he is on a JRE from 2015, here on a Google talk in 2017 and then there's a JRE from 2020. I think he too gives forecasts of when different things will happen, which is not so easy. Also, he has some criteria for when people will start to take notice that they might not have to die, and what will happen then. This too seems extremely hard to foresee; the fable about the dragon tyrant touches upon this question so I link it if someone didn't read it.
In case I misrepresented de Grey above, in the Google talk he classifies 7 damage types and gives maintenance approaches to each: Replace, Reinforce, Remove or Repair. Two damage types should be removed: "Death-resistant cells" and "Extracellular waste products". Do the senolytic drugs in development do any of these two, or is it something else?
I don't recall if de Grey ever used this specific terminology in his original formulation of the SENS strategy, but the current SENS Research Foundation page does mention senolytic drugs as a means of removing senescent sells under its "ApoptoSENS" initiative: https://www.sens.org/our-research/intro-to-sens-research/apoptosens/
I think the SENS strategy groups senolytics in with the general category of "removing dysfunctional cells" or "death-resistant cells."
(I don't think de Grey is directly associated with SRF these days, but they still seem to be using his basic framework.)
Since cell senescence is less than a third of aging, a very effective senolytic treatment could only ever slow, but not prevent aging.
Senolytic treatments are the closest of aging therapies to be put in use.
Other therapies such as injection of genetically modified and re-differentiated stem cells will be required in order to prevent and reverse aging
@MichaelDickens IDK
But at least some of it is:
1) DNA information loss (including Mito and other extranucleic genetic information)
2) Tissue level structural changes (scarring,thymus,skin, cardiovasculature, bone marrow &More)
3) Accumulation of poison and waste material in otherwise immortal cells like neurons (heavy metals, plastics, misfolded proteins/prions)
4) cell loss (overlaps with all of the above, this and the downstream effects is what Stem Cell treatments seek to remedy)
Quantifying by relative contribution in reduction of health (and death)
Every single aging damage must be accounted for in order to cure aging, naturally some are more imminently relevant than others and we should focus limited resources on preventing & repairing those damages which kill the most people at the youngest ages, or reduce the most QUALYs first.
I am unclear on what 'outside of trials' is supposed to mean. On the one hand, there are at present drugs that are already being prescribed outside of trials for slowing or preventing aging, off-label (take metformin). They clearly do so, if weakly. GLP-1 agonists might be prescribed off-label to slow or prevent aging, too. But on the other hand, it seems significantly less likely that the FDA approves a drug for the specific indication of slowing or preventing aging in this time frame (if only for logistical reasons). Is the latter what you're talking about? If the odd anti-aging doctor giving off-label prescriptions is acceptable, it should already resolve yes.
@lydia Metformin is not a senolytic drug: https://en.m.wikipedia.org/wiki/Senolytic
The description clearly requires only clinical use for aging, not FDA approval for aging. The bar is that the senolytic drug has to be approved for something, in some country, so that it can be used clinically, and then prescribed for aging. Since it also requires credible news articles or medical journals, it will presumably have to be somewhat legitimate and not just a rogue doctor. "Successful" is probably the part that will be most contentious.
@miller on a quick Google I can't find any evidence that it's a senolytic. Seems to delay cell senescence.
@miller market requires a new senolytic anyways, rapamycin has been studied since the 70s
@lydia My thinking is, it should be generally possible for an average person to get access to it (which wouldn't be the case with a limited trial), and there should be an overall medical consensus that it's expected to actually work. So if it's common for doctors to believe that something works to treat aging and to prescribe it off-label for that purpose, I would still count that, even if it hasn't gone through a formal approval process for that purpose.
Regardless of its exact mechanism of action, my impression is that rapamycin hasn't really passed that confidence bar yet; it's still something that a few people are self-prescribing based on a few inconclusive early trials.
I'm not totally sure at this point what my intent was with the "new" criterion. I wouldn't want to exclude, for example, dasatinib just because it was used clinically for other purposes and believed to be a potential senolytic at the time of market creation, if it does turn out to be a broadly usable treatment later on. I think my goal was just to indicate that, at the time of market creation, I did not believe that the status quo satisfied the conditions, and there would need to be some kind of visible advancement to qualify. (Which might be a literally "new" drug, or some kind of better understanding of the senolytic properties of an existing drug like dasatinib.)
You can put together an estimate of, for example, P&G's evaluation of P(anti-aging senolytic) from estimates of P(anti-aging senolytic by P&G | anti-aging senolytic by anyone (and) P&G invests X billion dollars) for a few values of X, an estimate of the market value of a working anti aging drug, an estimate of overall investment in senolytics and an estimate of P&G's investment in senolytics. I've tried to do this a few times and I can't value this market at 4%, let alone 40
@HastingsGreer Also the timeline is actually quite short. Demonstrating any kind of anti-aging effect will almost by definition require long followup time, so trials will be slow to complete... (there are some possible exceptions like a true elixir of youth with almost instant effects, but those are IMHO extremely unlikely to materialize)
I just searched and only found 2 current trials on clinicaltrials.gov with "senolytic" in the intervention.
The Alzheimer's one - most Alzheimer's drugs fail. It's only phase 1.
I just think that there is more interest in other anti-aging therapies right now, like reprogramming.
Maybe I'm wrong.
@MafeNoguera Such "ethical concerns" might cause media controversy or even impede FDA approval of such a drug, but are unlikely to stop research groups or doctors from testing such drugs. Those groups aren't restricted by vague concerns about social implications.
Since the resolution doesn't require widespread use, just reported successful use, I think this question boils down to whether senolytic drugs can be made to work well by 2023. If they are, some doctor or research group will test them and report success.