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A Layperson's Video Guide to a Few of the Therapies that Aim to Reverse Aging

Last month a couple of noted YouTube channels, in collaboration with the Life Extension Advocacy Foundation, published a set of popular videos that covered aging and the rationale for seeking to control aging through new medical technologies, aimed at laypeople unfamiliar with both the current promising state of the science and recent years of advocacy for rejuvenation research. The videos are quality productions and were quite widely viewed - a good job on the part of all those involved. We can hope that some of the many viewers will stop to think about how they can help to make this vision for the future a reality, and ultimately find their way to our community. The SENS Research Foundation and other groups working on the foundations of rejuvenation therapies need a larger grassroots movement and greater support if they are to make progress as rapidly as possible towards the realization of a complete suite of treatments to repair all of the cell and tissue damage that causes aging.

As a follow-up, the Kurzgesagt organization today published a second video that explaining at a high level the scientific basis behind a few of today's contending therapies: senolytics to remove senescent cells; NAD+ supplementation, such as via nicotinamide riboside; and some of the many varieties of stem cell therapies. Like the earlier videos it is well-crafted, and the more people who learn about the existence of senescent cells and senolytic therapies the better in my opinion.

Of these approaches, only the first is a SENS-like approach of damage repair, addressing a root cause rather than a secondary issue that results from some combination of root causes. Delivery of NAD+ attempts to override reductions that occur due to cellular reactions to rising levels of damage, a case of revving up a damaged engine. Present stem cell therapies work through signaling changes, temporarily making the signal environment less inflammatory and more conducive to regeneration - and the changes in cell signaling with aging definitely have the look of a reaction to damage, not a form of damage themselves. There is a future of stem cell therapies that involves replacing failing stem cell populations with new, fresh cells - but we are not there yet, and that is not what is achieved by near all present stem cell medicine.

The split of therapies in the video between those that have the potential to truly reverse aging by reversing its causes, and those that can only achieve more modest effects because they fail to address root causes is emblematic of the divisions in the present field of research and development. It is the case that immediately after the battle to convince people that extension of healthy life spans is possible, plausible, and desirable, comes the battle over exactly how to proceed. There are plenty of very different opinions on that topic. This is a much better position to be in, since it will eventually come down to hard evidence for and against specific approaches, as potential therapies are tested in animal studies and human trials - senolytics are very much more reliable and broadly effective in turning back measures of aging than just about anything else tried to date, for example. Nonetheless, this second battle is just as vital, lest time and funding be wasted on strategies that cannot possibly produce large and reliable gains.

The scientific effort to treat aging as a medical condition is still a tiny fraction of the efforts that go towards trying and failing to cope with aging, putting minimally effective patches on the symptoms, small and limited gains obtained at great expense. Of the efforts to treat aging, the majority of researchers and funding sources are not focused on what would be considered root causes in the SENS model of damage accumulation. The competing Hallmarks of Aging and Seven Pillars models overlap with SENS in theirs lists of causes, but some of them are clearly secondary effects from the SENS point of view, such as telomere length and epigenetic changes.

From an outsider's point of view, you'll see scientists backing senolytics, a true rejuvenation therapy that reverses a root cause of aging, and scientists backing NAD+ replacement, an attempt to partially compensate for consequences of the root causes, but which fails to actually address those causes. The former should be expected to be much, much better than the latter. But it'll take years for the studies to run through to prove that, and for the various champions to be vindicated or defeated. This will be the struggle for the next decade or two: to prioritize efforts that are much more likely to produce large effects on aging, and which are truly rejuvenation therapies capable of being applied again and again in the same individual for continued reversal of aging, rather than compensatory treatments that may produce modest benefits, but that leave the underlying causes of aging untouched and marching on to their inevitable conclusion.

Comments

Thanks for posting this Reason :)

Posted by: Steve Hill at November 3rd, 2017 6:36 PM

To be fair, SENS strategies haven't yet yielded better results in the lab than calorie restriction mimetics or other strategies that aim to boost innate repair mechanisms. I agree that long-term, the damage repair strategy holds more promise (though inducing massive innate repair mechanisms via Yamanaka factors or something similar is starting to look highly promising also). But for anyone interested in getting something right now, there's not that much more empirical reason to prefer a senolytic over something that promises to deliver nearly the same results as CR (though probably NAD+ upregulators fail short of the full positive effect of CR).
This is coming from a person (me) participating in the Longecity FOXO4-DRI group buy, btw-I do think the senolytics are very promising, but again, not substantially more so than more mainstream therapies if just measuring achieved lifespan gains in lower organisms.

Posted by: gheme at November 3rd, 2017 9:37 PM

@gheme: Yet calorie restriction doesn't achieve a fraction of all of the impressive things that even limited, one-time senescent cell clearance does when it comes to fibrosis, tissue elasticity, atherosclerosis, etc.

Posted by: Reason at November 3rd, 2017 9:48 PM

@gheme - If you are in that FOXO4-DRI buy group, hopefully you could take it on yourself to get a skin biospy stained for senescent cells. I think Reason mentioned in a previous post that this would be the only decent measure of if it is doing anything.

I don't know how difficult it is to arrange such a biospy though?

Posted by: Jim at November 3rd, 2017 11:36 PM

One thing I've been wondering is - how much did this video cost to make? And could videos like this be made each month (same topic regurgitated), with a call to action to carry out your own fundraiser, or donate?

I suspect a lot of the views will be because these videos were produced by youtube creators with a lot of subscribers. And obviously the creators are already very good at producing cartoon videos, which is talent that would have to be outsourced for monthly videos. But could this approach bring in money overall once costs have been taken into account?

On a more sober note the SENS cartoon videos on each of the classes of damage (which are pretty damn good) each have less than 10,000 views each:

https://www.youtube.com/watch?v=mJqnO_kNHCU

Posted by: Jim at November 4th, 2017 1:08 AM

It will be interesting to see if these videos bring in any new funding, as Kurzgesagt has a pretty large following out there.

Posted by: Ham at November 4th, 2017 7:16 PM

@Reason, do you know, are there any stem cell therapies clinical trials that show that new cells integrate into host tissue? I hear of Parkinson's desease but I may be wrong. I know it works fine for mice brain, however.

Posted by: Ariel at November 4th, 2017 8:18 PM

@ham This video has already brought in nearly 1k a month of new patrons and several hundred dollars of donations to MouseAge. We have also seen a massive increase in our followers on our social media platform. So yes this is absolutely working and has given us a huge boost.

Posted by: Steve Hill at November 5th, 2017 6:04 AM

I would also add that our Discord community is filled with hundreds of new people and a lot of people are saying they had no idea this field existed but are fascinated and supportive. There are a lot of people out there who are open to the idea it seems.

Once again like the previous videos the like/dislike ratio is massively in favor of rejuvenation too and once more reinforces what I said about the vocal minority not being the dominant feeling among the general public.

We are really pleased to meet all these new people, we have dozens of emails offering help and we are very very grateful for all the donations and support we have gotten in the last 2 days. Avalanche would be a good way to describe what has happened.

Posted by: Steve Hill at November 5th, 2017 6:08 AM

The comments in the comment section are also very positive this time. It seems like most of the the critics went somewhere else. There's also a noticeable increase (about 3 or 4-fold) in the number of new subscribers per day to the longevity group on reddit. I'd estimate about 700 of those arriving in the last days are due to your videos.

Posted by: Matthias F at November 5th, 2017 6:47 AM

Very glad to hear about all these positive developments ! Kudos to all involved !

Posted by: Spede at November 5th, 2017 8:14 AM

@Ariel: You might take a look at these reviews:

https://www.fightaging.org/archives/2016/12/looking-back-and-ahead-in-the-use-of-pluripotent-stem-cells-in-medicine/
https://www.fightaging.org/archives/2015/09/developing-stem-cell-therapies-for-parkinsons-disease/

Parkinson's disease work would be the place to look for evidence of stem cell therapies producing new cells that engrafted and survived. That sort of cell therapy is in a minority in the current practice in clinical medicine, even through it is the goal of a great many research programs.

Posted by: Reason at November 5th, 2017 8:22 AM

@Steve Hill, perhaps this is the public relations breakthrough that SENS has been hoping for. Perhaps more videos could be produced regularly on relevant topics such as current SENS research projects, Methuselah Prizes, etc. It just requires appealing videos made by an expert production company. It will generate more funds than it consumes.

Posted by: Morpheus at November 5th, 2017 8:45 AM

@Morpheus - I wouldn't crack open the champagne yet. People still have massive difficulty thinking about unpleasant seemingly inevitable things such as aging and death. So it could be a very long slog.

Although it will be interesting to see if a dam breaks in another area of research like it has in senescent cells. Obviously glucosespane is seemingly just some decent antibody markers away from being an active research topic.

Posted by: Jim at November 5th, 2017 12:31 PM

These videos are expensive to produce but yes they could drive the movement a huge amount if done often enough. But to circle back to an earlier article about advocacy by Reason - this level of advocacy isn't something that can be done by Zealotry and thus advocacy is equally as important as the research itself in many ways. We are starting to turn the tide though and pulling out all the stops here.

Posted by: Steve Hill at November 5th, 2017 1:25 PM

I'm glad there had been an uptick in funding. Also happy that the comments section has been more positive, which is a real change for this type of topic. I still think the vast majority is against or doesn't know about it yet, but more people on board is definitely a positive.

Posted by: Ham at November 5th, 2017 1:59 PM

The vast majority don't know and the vocal minority are against it based on our experience.

Posted by: Steve Hill at November 5th, 2017 5:30 PM

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