The Public Cannot Distinguish Between Scientific versus Unscientific, Likely Good versus Likely Bad Approaches to Longevity

One of the challenges inherent in patient advocacy for greater human longevity, for more research into aging and rejuvenation, is that journalists and the public at large either cannot or will not put in the effort needed to distinguish between: (a) scientific, plausible, and likely useful projects, those with a good expectation of addressing aging to a meaningful degree; (b) scientific, plausible, and likely unhelpful projects, those that will do little to move the needle on life expectancy, and (c) products and programs that consist of marketing, lies, and little else. This last category is depressingly large, and the first category still depressingly small.

There are examples of useful, high-expectation scientific projects in the senolytics industry, working on the means of removing senescent cells from old tissues. In animal models this is far and away the most impressive approach to rejuvenation attempted to date, applicable to many age-related diseases. The first good senolytic therapy will be revolutionary for human health in later life. As a counterpoint, an example of a poor and unhelpful scientific project is the use of metformin as a geroprotective drug, an approach that appears to very modestly and unreliably slow the progression of aging. Beneficial effects in animal studies are haphazard and small. The single study in diabetic humans shows only a small effect size. If devoting vast expense to clinical trials that target the mechanisms of aging, then why do so for a marginal therapy? Lastly, for examples of marketing and lies, one has to look no further than the established "anti-aging" industry and all of its nonsense and magical thinking. Apple stem cells. Random peptides with cherry-picked studies. Clearly no meaningful effects in the many humans using these products.

As meaningful attempts to produce rejuvenation therapies progress, and begin to attract greater attention in the world at large, we continue to see articles such as the one I'll point out today, in which no attempt is made to differentiate between sleep strategies, stem cell therapies, senolytics, metformin, and other approaches good and bad. High expectation versus low expectation of gains in health, good data versus bad data in animal studies, scientific or unscientific, it is all just lumped into the same bucket. This is unfortunate, as it leads to the situation in which any arbitrary health-focused demagogue selling branded coffee is presented just as legitimate and useful to the field as an industry leader in the clinical development of actual rejuvenation therapies, or another industry leader working on projects that can in principle only produce small gains in late life health. Which is clearly not the case. As a 60-year-old, you can practice changing your sleep and coffee habits, you can take a calorie restriction mimetic, or you can take senolytics, and only one of those three things is going to make a very sizable difference to your health and remaining life expectancy.

Why Silicon Valley Execs Are Investing Billions to Stay Young

Dave Asprey, 48, is the founder of the Bulletproof wellness empire and a vocal champion of the movement to extend human life expectancy beyond 100 years. He's made millions by experimenting on his own body and packaging his home-brewed discoveries into books, a podcast, consulting services and consumer products (you may have even tried his butter-laced coffee). Thanks to a recent explosion of advances in longevity medicine, Asprey's vision of living healthfully into his second century might not be so crazy. In fact, for people in middle age right now, a handful of therapies in clinical trials have the potential, for the first time in human history, to radically transform what "old age" looks like. If the life extensionists are right, a person who's 40 today might reasonably expect to still be downhill skiing, running a 10K or playing singles tennis at 100.

It might be an exaggeration to say BioViva CEO Liz Parrish believes death is optional, but for her, Asprey's goal of living to 180 shows a distinct lack of ambition. "If you can reach homeostasis in the body, where it's regenerating itself just a little bit faster than it's degrading, then what do you die of? An accident or natural disaster, probably. There's no expiration date at 90 or 100 years old." Like Asprey, she has received criticism from the longevity research community for becoming "patient zero" in her own experimental drug trial, aimed at halting aging at the cellular level. In 2015, Parrish underwent telomerase and follistatin gene therapies in Bogotá, Colombia. The procedures involved receiving around a hundred injections of a cocktail of genes and a virus modified to deliver those new genes into her body's cells.

Humans have always aspired to find the fountain of youth, so "people might be skeptical about the fact that anti-aging technologies are working now," says British investor and businessman Jim Mellon. "But the fact is that this is finally happening, and we need to seize the moment." Mellon cofounded Juvenescence, a three-year-old pharmaceutical company that's investing in multiple technologies simultaneously to increase the odds of bringing winning products to market. Mellon, 63, has made his fortune betting on well-timed investment opportunities, and he predicts that a new "stock-market mania" for life extension is just around the corner. "This is like the internet dial-up phase of longevity biotech. If you'd invested in the internet in the very early days, you'd be one of the richest people on the planet. We're at that stage now, so the opportunity for investors is huge." One of Mellon's bets is on a class of drugs called senolytics, which destroy senescent cells. Senescent cells harm the body by secreting compounds that cause inflammation in surrounding tissues. Many age-related conditions - arthritis, diabetes, Alzheimer's, cancer - have an inflammatory component, and studies suggest that a buildup of senescent cells is a large part of the problem.

Eric Verdin, 63, is president and CEO of the Buck Institute, a globally renowned center for aging research just outside San Francisco in Marin County. Verdin is bullish on the promise of living healthfully to at least 100. Today. But 180? Don't count on it. "My prediction, based on everything we know today, is that getting to 120 is about the best we can do for the foreseeable future. I'll bet my house we're not going to see anyone live to 180 for another 200 years, if ever. But making everyone a healthy centenarian, this is something we can do today. And that's something to be excited about." Verdin's own lab at the Buck Institute studies the aging immune system and how it's affected by lifestyle factors, such as nutrition and exercise. Take, for instance, rapalogs, a class of drugs derived from rapamycin that interact with a protein called mTOR, which serves as a linchpin for multiple critical biological processes, including cell growth and metabolism. Rapalog drugs tamp down mTOR, possibly preventing age-related diseases such as diabetes, stroke, and some cancers. One of the many effects of rapamycin is that it mimics the mechanisms of calorie restriction. As Verdin's lab and others have shown, fasting provides a number of anti-aging benefits, including insulin regulation, reduced inflammation and, to put it colloquially, clearing out the gunky by-products of metabolism.

Comments

When the public sees Unity Biotechnology destroying $900 million of its investors value, maybe some of the shills in the longevity world should take a long look in the mirror, and stop whinning about Liz Parrish and her nonsense

Posted by: Jim Burnbae at August 20th, 2020 3:39 PM

Well before you go off on the ignorant public consider the fact that most scientists think de grey is full of it and that crying s is pseudoscience but your signed up for it as I understand. What do you think of this https://bigthink.com/videos/why-cryogenics-is-bogus I've been following this site since early 2006 and all I've seen are interesting stories but it doesn't seem like we're much closer to actual therapies. Why would it be different in another decade and a half

Posted by: J at August 20th, 2020 6:56 PM

@J
Just in the last few years there were some serious progress with reversing most of the aging hallmarks in cells with partial programming which done by turn.bio and Salk institute. there are senolytic drugs being developed including human trials. there are glucosepane(the main AGEs in the body) breaking enzymes that were discovered and being developed for therapeutic use and this is just part of the list of the progress done mostly in the last three years.
So how you say there were no progress since 2006?, it doesn't look like you read much of this blog or even watch the news because some of the progress I mentioned got published in the mainstream media.

Posted by: golden axe at August 20th, 2020 7:54 PM

@J
And who are those "most scientists"?, Aubrey de grey was one of the firsts in the field of fighting aging but today there are many companies and scientists in the field.
There was never a serious scientific criticism against Aubrey goals of fighting aging, many scientists are trying to solve problems more complicated than aging without the "criticism" anti-aging science had faced mostly in the past because of cultural norms and nothing more.

You are stuck in 2006. many things have changed in the last 14 years.

Posted by: golden axe at August 20th, 2020 8:07 PM

@golden axe I try to keep up with the blog but I do go stretches without seeing it so I doubt I miss things. I'm simply giving my honest assessment Here, I hope I'm wrong in my pessimism. Maybe it's time to seriously consider cryonics ( though most scientists think it's bogus) and I'm saying that as among the younger cohort of readers of this blog. In a purely hypothetical scenario where cryonics was guaranteed to work I'd opt to be sure Suspended at 18 as I have no desire to go through any of the aging process. It's also clear my values differ tremendously from the author of this blog.

Posted by: J at August 20th, 2020 10:10 PM

The truth is no one knows exactly what will work. We do know a lot of approaches that do not work, however.

Part of the problem is inappropriate mice models.

Also there are various approaches that are marginal in terms of benefits, but the right combination with other marginal therapies may well unlock significant gains in lifespan because enough of the age driving pathways are being hit at once.

There is also the possibility that an area of investigation may come out of left field and surprise us with its effectiveness; plasma fractions are an obvious example.

Posted by: Mark at August 21st, 2020 3:11 AM

The unity failure was bad news. I'd still really love to see someone trial a whole body senolytic for knee osteoarthrhitis. But it might also be one of those diseases where once too much cartilage is gone, removing senescent cells won't do much, only recreation of the cartilage would help.

I get a feeling of pain when reading about Liz Parish, she seems like a missed opportunity. The clinic she is building down in Colombia seems to be turning into the Telomerase gene therapy version of those dodgy stem cell clinics in the US. All promises and no data. There is a tested model out there for using paid research in a positive way (https://medium.com/mosaic-science/a-plutocratic-proposal-deba1f979bff) but I dont think Liz will go down that route.

There is also the fact that Liz is an attractive looking person, rather than a middle aged or old bloke, which naturally means more people will be open to her ideas. Just look at renaissance paintings, they were paid for by the catholic church or patrons, but even back then those people knew that if you wanted to sell an idea you'd use the image of a young attractive woman.

Oh well, sooner or later a senolytic therapy will achieve good results in the clinic in a larger trial.

Posted by: jimofoz at August 21st, 2020 5:35 AM

Why do we see this pattern again and again?
"I'll bet my house we're not going to see anyone live to 180 for another 200 years, if ever."
->
"I think there is a world market for maybe five computers."
Thomas Watson, president of IBM, 1943

Posted by: Nick Westgate at August 21st, 2020 7:55 AM

@J: You want to be frozen at 18 to avoid the aging process? You must be older than that if you have been following cryonics since 2006, so you know that you are not old in any meaningful way for years after the end of your teens.
BTW, I am all for cryonics too, even if at 40 I am pretty sure that I will benefit from many "real" rejuvenation therapies before having a shot at being cryogenically preserved with an even minuscule chance of success.
The way I see it, the problem is not the difficulty of revival in the future, rather the near impossibility of decent preservation - with optimal perfusion minutes from death - in the present. All the fantastic lab results in the world won't change the fact that until there's a massive paradigm shift in the legalities and logistics of death, cryonics won't save a soul. The field is snake oil not because its premises are faulty, but because implementation is nigh to impossible.

Posted by: Barbara T. at August 21st, 2020 9:39 AM

@Nick Westgate: It blows my mind that some people are "sure" of what science will look like in 180 years when they can't even predict what will happen in the next 12 months. Cognitive dissonance at its wildest.

Posted by: Barbara T. at August 21st, 2020 9:46 AM

I think one of the big mistakes we've made is to allow "damage repair" and "reduced metabolism" themes to dominate our thinking. Rather, we should be looking for upstream levers that prevent damage while maintaining a youthful metabolism. In other words, we need to ultimately tweak the aging program itself, rather than making minor adjustments to the current program's input (such as diet and exercise), or cleaning up the current program's output (damage repair - a last resort).

Posted by: dtkamp at August 21st, 2020 10:21 AM

@Barbara T.

Well yes I'm older than that, but I'd been following this site for a few years prior and I've been interested in life extension and cryonics since the age of 12, not everyone fits into stereotypes of younger people being braindead morons who can barely consider the future a few months down the line. So yes back then I would have chosen if it were possible to know it would work to be suspended and old is a matter of perspective, I want as little damage as possible. Yes the same laws that restrict people taking advantage of cryonics optimally are the same ones that will prevent access to rejuvenation therapies for a significant period of time.

Posted by: J at August 21st, 2020 2:50 PM

A good analogy is face cream. A zillion products, a zillion studies, all claiming this or that percent improvement. The bottom line however is that, not counting sunscreen protection, not a one of them really move the needle. There is no cream that makes enough visible difference to actually make anyone look more than a couple years younger. The expensive ones especially are not worth the time and cost. Somewhat promising ingredients are just that - somewhat. And nobody combines more than 2 or 3 actual actives, you have to decide on either or...when you probably need 20 in a product.
I'm hoping that either oneskin or alive by nature can actually move the needle because they work by killing off senescent cells in the skin. Now that's a technology that just might make one look better than 3 years younger. After years of cosmetic marketing crying wolf I'm not holding my breath on anything though. Take a face from 60 back to 40, or 25 - then we might have something.

Posted by: august33 at August 21st, 2020 3:11 PM

@J. "The same laws that restrict people taking advantage of cryonics optimally are the same ones that will prevent access to rejuvenation therapies for a significant period of time."

Not really. Cryonics costs 200K if one doesn't buy life insurance decades in advance, and this doesn't include the tens of thousands that you'll need if you want to await death in a clinic that's enlightened enough to call the stand by team before your brain starts to rot. Let alone that for the billions of people who live far away from, say, Scottsdale or Moscow, the idea of dying alone, separated from loved ones who are unlikely to be able to drop everything and sit in a foreign hospital for weeks, is not that enticing. And this scenario is for the lucky ones, because get a death that doesn't announce itself in good time, i.e. the majority, and all your best laid plans go flying out of the window.
Can't see how taking a course of senolytics, getting gene therapy, or having an infusion of OSKM factors would be that problematic or such a gamble. Even cost, which is likely going to be high at first for in vivo editing, will drop quickly, while the same could be said for cryonics only if the procedure magically became as common as cremation. They'll invent a time machine before that happens.
The insurmountable problem of cryonics (on top of many others) is infrastructure.

Posted by: Barbara T. at August 21st, 2020 7:59 PM

@August33: "I'm hoping that either oneskin or alive by nature can actually move the needle because they work by killing off senescent cells in the skin."
But with such a narrow focus, wouldn't they incur in the exact same problem that Unity is experiencing now?
Also, a huge portion of facial aging is caused by loss of bone and muscle, so no skin treatment will ever take a face from 60 back to 25 (or 40).

Posted by: Barbara T. at August 21st, 2020 8:07 PM

The whole waiting around in a clinic wouldn't bother me, but i am very sceptical of the prospects of it working. If assisted suicide was legal across the board though couldn't they just " put you under" at NBC a clinic on arrival and then commence the cryonics procedures? Ya the cost is and probably will continue to be prohibitive

Posted by: J at August 21st, 2020 8:28 PM

@Barbara T. - OneSkin might have a chance since aged skin is a huge contributor to the aged SASP, and if you knock down SnCs in the epidermis, you'll also be knocking down the systemic SASP which will benefit every organ/tissue in the body. Unity couldn't use its treatment systemically due to toxicity so was forced to employ it only locally; since they didn't reduced the systemic SASP they never got regeneration of cartilage in their animal model (and presumably also not in their human trials). That is why I predicted problems for their Phase 2 a year ago.

Posted by: Gary at August 21st, 2020 10:59 PM

@J. You can get euthanised in Oregon or Switzerland and have a stand by team at your bedside, but how much does that cost? And again, this assumes that everything falls into place perfectly, by which I mean you get a disease that doesn't kill you suddenly (even with cancer you can crash just when you think you've turned a corner) and manage to coordinate everything to perfection. Given how unknowable the odds of being revived are, and they are likely in the single digits, even someone with a terminal disease would be better off on a clinical trial, so very few would choose euthanasia even if they could both afford and organise it.
My point is that cryonics would be a realistic option only if all hospitals in the world had a team to cool down and perfuse whoever dies, of whatever they die, as soon as they die.
It's not about lowering the cost of cryonics to make it more affordable, or pushing its inclusion in life insurance policies. The field requires a huge investment in infrastructure, which is not going to happen without a huge shift in our collective mentality, which is going to happen even less than making anti-aging a political priority given that freezing bodies is seen as more outrageous than rejuvenating them.
I will definitely consider cryonics if nothing else comes first, but from a societal perspective it's a chimera.

@Gary: Thanks!

Posted by: Barbara T. at August 25th, 2020 8:56 AM

@Barbara T.

I don't think it's feasible right now as a society wide thing, but I still don't see much I terms of anti-aging. You mentioned cancer and that's a good example to make my point about how far off we are profess wise. Millions will continue to die From it, this despite the fact that there is enormous funding of the top minds in the world working on the problem and near unanimous public support for defeating cancer which has been going on for decades. In contrast to this, life extension research has none of this and is looked at as a fringe field populated by weirdos with the overwhelming majority of the public being either largely indifferent or overtly hostile to the idea. Also I don't feel that many of the people in it interesting, a lot of boring middle aged or older people living boring lives who just want to continue living those boring lives longer. exhibit A https://www.fightaging.org/archives/2013/01/vision-and-efforts-made-to-live-longer/

Exhibit: B https://www.fightaging.org/archives/2016/07/finally-signed-up-for-cryopreservation-the-existence-of-a-fallback-plan-is-great-but-only-if-you-actually-take-advantage-of-it/

Posted by: J at August 25th, 2020 1:05 PM

@J. Let's say (numbers out of my a*** but ratio likely accurate) that proper rejuvenation is 50 years away and cryonics 500.
What's your objection?
That we shouldn't pursue anti-aging because we are not there yet? Or that anti-aging is a bad idea because people interested in it are "middle aged or older" and (god forbid!) "boring"?
So, who is rejuvenation for, 25 year old rock stars?
I am not following you...

Posted by: Barbara T. at August 25th, 2020 3:28 PM

@Barbara T. Well I don't understand wanting to live longer just to do boring things

Posted by: J at August 29th, 2020 9:25 AM

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.