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The Popular Press in Better Form on Senolytic Research and Development

Research programs and investment in commercial development related to senolytic therapies are growing rapidly, particularly in the last couple of years. As today's article demonstrations, journalists in the popular press are improving when it comes to their ability to report sensibly on these developments. This has taken far too long to come to pass; it wasn't all that long ago that near every article in the media on the prospects for treating aging was some combination of nonsense, scorn, and fear-mongering.

Senolytic treatments are those that selectively destroy senescent cells in aged tissues. The accumulation of senescent cells is one of the root causes of aging; even in small numbers these errant cells cause chronic inflammation and degrade tissue function in numerous ways via the signal molecules they generate. Removing senescent cells is a form of rejuvenation, capable of reversing aspects of aging and age-related disease and extending healthy life span. The data in mice is robust, impressive, and expanding. The first human data will be published over the course of the year ahead.

Clearance of senescent cells as a way to intervene in the aging process has been recognized as a plausible goal for quite some time, and in fact was in the SENS rejuvenation research proposals from their inception around the turn of the century. Unfortunately, aging was not seen as a legitimate target for therapy at that time, and obtaining support for this line of work has required long years of advocacy and philanthropy. In a better world, in which the research community had not relinquished its duty in the matter of aging for the better part of a generation, this all could have happened two decades or more before it finally arrived.

These days there seems a certain eagerness to forget the years in which the SENS program was mocked, researchers dismissed the likely relevance of senescent cells to aging, and the talking heads of the media sneered at the idea of treating aging as a medical condition. It is now said that nothing could have happened any faster than it did, that in fact everyone was doing the right thing just as soon as they could. This is self-serving nonsense. Countless lives have been lost and continue to be lost because of entirely unnecessary delay in the matter of addressing aging and age-related disease as an urgent concern. Senolytics is just one branch of many needed approaches. Most of the others, biotechnologies that could be just as influential on the progression of aging, are still minority concerns, disregarded by the research community, the press, and the public at large. Much work remains to be accomplished.

Want to live for ever? Flush out your zombie cells

Two blown-up images of microscope slides are the same cross-sections of mouse knees from a six-month-old and an 18-month-old animal. The older mouse's image has a splattering of little yellow dots, the younger barely any. That staining indicates the presence of so-called senescent cells - "zombie cells" that are damaged and that, as a defence against cancer, have ceased to divide but are also resistant to dying. They are known to accumulate with age, as the immune system can no longer clear them. They have been identified as a cause of ageing in mice, at least partially responsible for most age-related diseases. Seeing the slides, it makes me worried about my own knees. "Tell us about it," says Pedro Beltran who heads the biology department at Unity Biotechnology, a 90 person-strong company trying to halt, slow or reverse age-associated diseases in humans by killing senescent cells. "We think about it all the time... Wait until you see your brain."

Developing therapies to kill senescent cells is a burgeoning part of the wider quest to defeat ageing and keep people healthier longer. Unity, which was founded in 2011, has received more than $385m in funding to date. Its first drug entered early clinical trials in June, aimed at treating osteoarthritis. Other startups with zombie cells in their sights include Seattle-based Oisín Biotechnologies which was founded in 2016 and has raised around $4m; Senolytic Therapeutics whose scientific development is based in Spain and which was established last September; and Cleara Biotech, formed this June backed by $3m in funding and based in the Netherlands. In addition, Scottish company CellAge, also founded in 2016, has raised about $100,000 to date, partly through a crowdfunding campaign.

"The concept is totally getting the imagination of investors because it isn't about just slowing down the clock but actually turning it back and rejuvenating people," says Aubrey de Grey, who for nearly a decade through his campaigning charity the Strategies for Engineered Negligible Senescence (Sens) Research Foundation has been urging scientists to work towards eliminating ageing and extending healthy lifespan indefinitely. "I've never seen a field grow so quickly," says Laura Niedernhofer, a researcher who studies ageing at the University of Minnesota Medical School, adding that there isn't even as yet any human data. "There is a recognition that there is potential here to go to a root cause of ageing."

To date about a dozen drugs have been reported that can mop up zombie cells. Clearance of the cells in mice has been shown to delay or alleviate everything from frailty to cardiovascular dysfunction to osteoporosis to, most recently, neurological disorders - though whether killing senescent cells extends life is complicated. Most of the benefit seen in mice seems to be in extending healthspan, the time free of frailty or disease, and as a result median lifespan. True longevity - the maximum time the animals remain alive for - remains relatively unchanged, though studies show a 36% extension of remaining lifespan in mice that were treated when they were very old.

Unity's method is based on targeting the biological pathways senescent cells use to resist the normal death of ageing cells. Inhibit the right pathway and death can be "nudged" to occur. The company's approach is to find small molecules (so called "senolytics") that can do this. Oisín is trying to do something more ambitious: killing all a person's zombie cells in one go. The idea is to load the body with nanoparticles that insert a "suicide gene" into every cell. It only triggers if a cell has a lot of a particular protein (p16) that acts as a marker of zombie cells, albeit imperfectly.

Oisín is planning to run what co-founder Gary Hudson calls a "stealth ageing trial" in people with a variety of late-stage cancers next year (there are lots of cancers for which no treatment is available so the regulatory bar to the clinic is lower). That will test a version of its anti-ageing therapeutic modified to target cancer, but it may also be possible to see - by virtue of observable age characteristics - whether the drug has had any effect on senescent cells.

If eliminating senescent cells does improve specific age-related diseases in humans, the next step will be to go broader. That's tough because regulators don't recognise ageing as a treatable condition. On the positive side, if there is an eventual treatment it wouldn't have to be taken every day. Imagine an annual or biennial therapy, starting from middle age, that sweeps away any senescent cells building up. And because you wouldn't chronically be on the drug, the risk of side-effects would be minimised.

Comments

The title of the article is awful and sensationalist. Which, in turn leads to the comments section being full of the nonsense, scorn, and fear mongering that you mentioned.

Posted by: Ham at October 8th, 2018 3:28 PM

Blame the editors. The writer doesn't get to choose the headline.

Posted by: Gary at October 8th, 2018 3:46 PM

The reason the editor did that is sensationalist and inflammatory titles are how you sell your magazines.

Basically 'do you want to live forever', you know is going to shock peoples paradigms and enrage them. Which then they read the article to see where you are 'wrong'.. and even take the time to comment on the article.

The stronger the argument in the article, the more people will read it and be enraged.

Posted by: aa3 at October 8th, 2018 11:13 PM

@Aa3
Ironically, living forever is too abstract and remote that people take it as some rhetoric metaphor.

On the other hand, a functional cure for back abd/or knee pain is something close and concrete enough to be believed

Posted by: Cuberat at October 8th, 2018 11:51 PM

The Guardian article's title is annoying, but overall the article is a net win for senolytics and anti aging publicity.

A title like "Do you want a cure for your sore knee" would have been much better, but I guess you've got to pay the piper in some way.

I've tried to tell my flatmates in the past about senoltyics, but their eyes instantly glaze over and they act like they think I am a crazy person. I whatsapped this article to a flatmate, she said she hasn't read it yet... but it is there, and it is from a well known newspaper so it is harder to dismiss. Do I think my flatmates will ever donate and support this research? Nope. Do I think they will use senolytics in the future? Yep. I guess articles in the mainstream newspapers are useful as the message will reach more people who are receptive.

Posted by: Jim at October 9th, 2018 3:49 AM

At least senolitics are getting a good press. In the news they might replace the stem cells, which have been the miracle cure of tomorrow.. for the last 20 years.

senolitics have much less moral objections from the conservatives and the required investments are much lower, v while the payback much sooner that I don't see much resistance

Posted by: Cuberat at October 9th, 2018 8:35 AM

I really wish there were quick and easy ways to get better monitoring of my body so I can run experiments. Some of these senolytics are actually available to the general public right now, but without any sort of baseline or measurement, trying them out doesn't make nearly as much sense.

Posted by: Dennis Towne at October 9th, 2018 11:46 AM

@Jim,

Unfortunately "do you want a cure for your sore knee" is what a lot of people want, and nothing more. At least by reading what tons of people say in every one of these articles, they supposedly want to die on time, but in good health.

@Cuberat

Senolytics get just as much flak from internet commentators as the next thing. 'Ethicists' are more 'comfortable' with senolytics because they supposedly won't have people live longer, but just healthier longer. Can read it in this article here: https://www.politico.com/agenda/story/2017/12/13/anti-aging-research-drugs-000595

But here is the snippet I was alluding to:

"Ethicists are also more comfortable with senolytics than some other anti-aging ideas, because the drugs aren't intended to extend how long we live, but improve how well we live. The goal is to achieve what McGill University bioethicist Jennifer Fishman describes as the "ideal form of aging": to be healthy until right before you die. People would experience more years of healthy, active, dementia-free life and then a briefer, more merciful final illness."

Everything is fine until people might live longer it seems. Ugh. We'll see if the allure of tons of money outweighs these 'ethical and moral concerns'.

Posted by: Ham at October 9th, 2018 12:12 PM

A quite good article. They did their homework, particularly on the current state of the field (including referencing a senolytics company I didn't know). Probably they had a long conversation with Aubrey.

Posted by: Antonio at October 9th, 2018 1:08 PM

@Ham, "the drugs aren't intended to extend how long we live, but improve how well we live", so are you saying w/o any additional progress in rejuv, we will still die on time, at about 80 years old?

Also, does anyone know what the average "Healthspan" is currently?

Posted by: Robert at October 9th, 2018 1:14 PM

Robert,

I don't know. But I'm of the mindset that if you're healthier for longer, you're probably going to live longer. If you're continually healthy why would you suddenly drop dead, right? But who knows. What I do know is that I'm (and I assume others will be as well) going to be quite upset when so called 'ethicists' try and hold up things or try to decide how long people can live because something makes them uncomfortable.

Posted by: Ham at October 9th, 2018 2:38 PM

@Ham,Antonio ,Robert
If we can live up to 120 and be healthy and active, then we can actually talk about exceeding the lifespan. For somebody in early forties, like me that sounds like forever, though

Posted by: cuberat at October 9th, 2018 3:16 PM

@cuberat: I'm in my middle forties and it don't sound like forever at all. And much less so when I look at the my parents in their early seventies, with sarcopenia, osteoporosis, the first signs of dementia and what not. They don't have a second to lose.

Posted by: Antonio at October 9th, 2018 4:25 PM

Thanks guys for your thoughts/comments. I am rubbing shoulders towards 60 (yikes, where the hell did time go?) I visually being on a merry go round, and it is spin faster with each revolution as an analogy.

I was asking about healthspan because I thought a few people live to 120, so if Solyntics increase our healthspan W/O increasing lifespan, that is the number we could be looking at, to live. If so, it would be awesome cause imagine if we have a number of decades to improve lifespan (40-60 years before we hit 120) it should be a no brainer for the possibilities (LEV)

And, assuming exponential increase in medical knowledge, even better.

Posted by: Robert at October 9th, 2018 5:03 PM

@Antonio
I was talking about the hypothetical scenario where you have rejuvenation technology to help you live healthy up to 120 but not actually extend the max lifespan
if you are ~45 and expect to live to 120-125 it is like you have 80 more healthy years in front of you. Even for your parents, if tomorrow there was a pill that can give good chances to live up to 120, it would seem like a long ahead.

Of course, we don't expect to live 120y. So even forties seems a bit old... And

Posted by: cuberat at October 9th, 2018 5:08 PM

Say with current medicine some person who is 65 has kidneys going downhill fast, and realistically they will be dead by 75 at best. But then new senolytic drugs for their kidneys are able to repair some of the damage to the kidneys and stop further damage. Now the person might make 90, with a dramatic increase in their remaining health span.

Now imagine a flood of similar drugs that are for many organ systems in our body.

Posted by: aa3 at October 10th, 2018 2:57 PM

Ham: I agree, improving health is what leads to longer life expectancy.

Posted by: aa3 at October 10th, 2018 3:00 PM

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