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Disruptive Change in Aging Research Arrives from the Outside

Disruption is a part of progress. All communities of research and development go through cycles in which (a) the established mainstream and its insiders become slow and ineffective, (b) outsiders become frustrated given the unrealized potential for faster progress and better outcomes, (c) some of these outsiders succeed in developing a vastly better path forward, despite being opposed at every turn by the mainstream, (d) the new path forward displaces the existing mainstream, and the outsiders become the new leaders and insiders, (e) with time, this new mainstream becomes slow and ineffective. So the cycle repeats.

In the matter of medicine, aging, and longevity, we are presently somewhere in the midst of step (c). The mainstream of ineffective, expensive approaches to the treatment of age-related conditions is ineffective and expensive because it fails to consider or address the root causes of aging. Try making any damaged machine work better and longer while not actually repairing the damage - it isn't easy. The typical approach to research is to start with the end stage disease state and work slowly and painfully backwards through a very complex dysfunctional metabolism. At the first proximate cause, stop and try to build a treatment that can manipulate the diseased metabolic state so as to make the proximate cause less onerous to the patient. Then return to tracing the disease backwards towards root causes. There are so many layers of proximate causes in most diseases that this type of approach can continue - and has continued - for decades without ever getting close to the cell and tissue damage that is the root cause of aging, and thus the root cause of all age-related disease.

This, however, is the mainstream, the default approach. It is an established culture, reinforced by regulation and tradition, and will change but little without disruption. The most important outsiders attempting to disrupt aging research in favor of effective progress towards treatment of aging are those of the small community that built and supported the Methuselah Foundation and SENS Research Foundation, pulling in philanthropic funding and gathering allies in support of a repair-based approach to the treatment of aging. The fundamental, root causes of aging are well cataloged, forms of cell and tissue damage caused by the normal operation of metabolism, so why wade through the mud of how exactly aging progresses in detail from these causes, and why start at the end and work backwards? Just fix the known causes using any of the envisaged and planned potential classes of repair therapy and see what happens. The potential for cures first, full understanding later: too many people are dying to indulge the mainstream's preferred approach.

We are far enough into this process of disruption that some outsiders have become scientists and some scientists have joined the insurrection. There are thousands of supporters of rejuvenation research, there is respectful and informed press attention, and tens of millions of dollars have been deployed to advancing this cause. The first rejuvenation therapies are under development in startup companies. We're almost at the stage where the people who at the beginning carried out the hard, thankless work of spreading new ideas, obtaining support, and kicking shins - telling the scientific community that they were going about everything the wrong way - start to be buried by the second wave. It is the fate of all pioneers to be forgotten and trodden upon by a collaboration between later newcomers, those with more resources to claim the mantle of leadership, and those of the former mainstream who decide to pretend that they agreed all along. Such is life. It is frustrating, but the important thing is not the credit, but that the job will be done, that repair-based therapies for aging will become the new mainstream on the basis of obtaining far better results than the present approaches to aging. Life and health before pride.

The article linked below struck me as exhibiting a nice mix of many of the agendas that come to the fore during the disruption of an industry, ranging from the several factions intent on burying the original disruptors to individuals with the mainstream attempting to present a slight adjustment of their methods as an alternative to the still vastly better disruptive technology. I'm not sure I agree with all of the core thesis. Some of those presented as outsiders, such as Larry Ellison and Paul Glenn, were almost immediately co-opted by the mainstream of the time. There isn't enough of a distinction made between for-profit and philanthropic funding, as the latter has been vastly more influential and important over the years in which I've been observing progress in aging research. But see what you think.

Despite the hyperbole, private funding is changing the science of aging for the better

I've been led here by Sonia Arrison, a Silicon Valley local and author of 100-Plus: How the Coming Age of Longevity Will Change Everything. Arrison has agreed to show me around her strange Californian world, populated with very wealthy, very smart dreamers, who share her certainty that a longevity revolution is on its way. We've arrived on Joon Yun's doorstep to learn how and why he, along with a small group of big power players, plan to "cure" aging and extend human health span - and possibly even human life - by decades, if not centuries. "I essentially made a wager to myself that aging is a code," Yun explains to me from across a shiny conference table. "If aging is a code, that code could be cracked and hacked. The current system in healthcare is a whack-a-mole of your symptoms until you die. It addresses the diseases of aging, but not curing the underlying process behind aging itself. The healthcare system is doing a good job of helping people live longer and stronger lives, but aging is still a terminal condition." In 2014, Yun created the Race Against Time Foundation and Palo Alto Prize, which will award $1 million to a team that can demonstrate the capacity to mitigate aging by, among other things, extending the life of a mammal by 50 percent.

Faith that science will conquer aging is common in Silicon Valley these days. The language Yun uses to explain his dream - especially the use of the word "cure" - makes traditional researchers in the field of aging cringe. But few are complaining about the interest of the big-spending Silicon Valley crowd. In recent years, public institutions like the National Institutes of Health have been slow to commit any more than a token of their overall budgets to aging research. It is the private funders with big dreams who are galvanizing the field. The Ellison Medical Foundation has spent nearly $400 million on longevity research. Oracle founder Ellison told his biographer, "Death makes me very angry." PayPal cofounder and venture capitalist Peter Thiel helped fund the SENS Research Foundation, a longevity organization co-led by British gerontologist Aubrey de Grey, who's argued we might someday halt aging and extend life indefinitely. (Arrison, Thiel's longtime friend, introduced the two).

In 2013, the founders of Google launched Calico, short for California Life Company, to research aging and associated diseases. A year later Calico teamed up with the biopharmaceutical company AbbVie, with which it plans to invest up to $1.5 billion to develop age-related therapies. "With some longer term, moonshot thinking around healthcare and biotechnology, I believe we can improve millions of lives," wrote Google cofounder Larry Page. The quest to extend longevity makes perfect sense in Silicon Valley, explains Lindy Fishburne, a longtime lieutenant of Thiel's, in her stately office in San Francisco's Presidio, a former military base that sits on a pictorial tip of the San Francisco Bay. "It's the engineering culture which says we'll build our way out of it, we'll code our way out of it, there has to be a solution. I also think it's coupled with a very unique optimism that is pervasive in Silicon Valley."

It is worth noting that all too few of the people and funding sources mentioned in the article are in fact backing the repair-based approaches to rejuvenation that are, to my eyes, the most likely to realize a future of greatly extended healthy lives, and to accomplish these gains soon enough to matter to you and I. Many of those involved are either already or on their way to being captured by the present ineffective mainstream, just like Ellison and Glenn. Nonetheless, disruption is underway, and threads of meaningful work will continue to grow. It is still early enough in this process that ordinary folk like you and I can make a mark: our philanthropy and support for the SENS Research Foundation and similar organizations in past years has produced meaningful change in the status quo, and that change is spreading.

Comments

Someone posted a link to this in /r/longevity, so i'll give the same response.

While this is a very good and thorough article, I think it went too easy on the pro-immortality crowd. It didn't illustrate the tremendous challenges that still need to be overcome. The fact is that despite our progress we're still largely in the dark as to the aging process. There are still many gaps in our knowledge. And even when we get new knowledge, it's a whole different challenge to transform knowledge into actual medicine. If real anti-aging medicine is possible, it's a long way off.

Posted by: MissKaioshin at May 28th, 2016 12:20 AM

Obvious troll is obvious.

Posted by: Antonio at May 28th, 2016 2:31 AM

Antonio, completely agreed. Always same comments from her. She must be bored, naive, or looking for a reaction.

Posted by: Robert Church at May 28th, 2016 2:41 AM

There's some weird compulsion with this one. I'm not sure why she feels the need to copy/paste the same stuff over and over again. Her opinions might have some weight behind them if she worked in a relevant field instead of being an internet layman with zero credibility, but alas, that isn't the case. It never ceases to amaze me how she thinks she knows more than everyone else though. Awesome.

Posted by: Ham at May 28th, 2016 3:45 AM

MissKaioshin you are not a researcher so you do not know what we are doing in the lab. Stop with the negative crap we all KNOW how hard the task is without people like you grinding down our will to try.

Great Article reason thanks! New allies are arriving and more researchers are stepping forward to state that aging is something that can be controlled. This is why ICD-11 is critical to change this established view and open the floodgates!

Oh and also if you can spare even the cost of a starbucks grande please consider a donation to our Senolytics program on lifespa.io

https://www.lifespan.io/campaigns/the-major-mouse-testing-program/

Posted by: Steve Hill at May 28th, 2016 5:56 AM

Steve Hill:
No, I'm not a researcher, but neither are most longevity enthusiasts. I haven't said anything that was supported by the vast majority of experts in medicine, genetics, stem cells, biotechnology, etc. Yes, more scientists are agreeing that aging is a biological process and it has mechanisms that can possibly be manipulated, but that's way different from saying that aging treatments are around the corner. Most scientists are very skeptical. Can they be wrong? Of course they can. But I think it's good to maintain a healthy skepticism.

I'm not trying to grind down anyone's will to do anything. It's good that we have people who are willing to pursue these lines of research despite what the majority believes. But we also need to be realistic about our expectations.

Posted by: MissKaioshin at May 30th, 2016 1:52 PM

"I haven't said anything that was supported by the vast majority of experts in medicine, genetics, stem cells, biotechnology, etc."

LOL, there's supposed to be a NOT in between "was" and "supported". Now I'll never hear the end of it. :)

Posted by: MissKaioshin at May 30th, 2016 1:53 PM

You say its good to pursue these lines of research despite what the "majority" believes, then you proceed to constantly try and discredit and denounce anything that anyone involved in the research has to say. All while not being a scientist yourself. Makes total sense.

Posted by: Ham at May 30th, 2016 3:25 PM

She thrives on us engaging. The only way to make her go away is to ignore her always and forever. As long as she thinks that she can get a reaction... she will be back.

Posted by: Barbara T. at May 30th, 2016 4:07 PM

A plea for civility.

First, while MissKaoshin has occasionally seemed somewhat unreasonable in her level of skepticism, most of her comments are well within the range of reasonable skepticism. We are a very small community and are constantly confronted by completely ignorant, knee-jerk incredulity (rather than true skepticism) and/or ideological hostility, and I think it sometimes makes us overly-sensitive. Contrariwise, people who are ideologically on "our side" make far less reasonable comments about the potential of particular therapies or prospects and timelines for a comprehensive medical solution to aging without challenge here on FA! and in other communities favoring intervention in aging all the time.

If we are to make real progress toward our goals, we need to be able to engage respectfully with reasonable critique from the wider public and from scientists who have not yet been brought on board with our goals and strategies. It's also critical that we avoid the dangers of group-think, and of drinking our own Kool-Aid generally. And, finally, and without intending to insult anyone, we don't want people who are curious to come into our discussions for the first time and see discussion threads that look like a cult that is intolerant of heretics and heathens.

Posted by: Michael at May 30th, 2016 5:36 PM

I don't find her *reasonable* at all. She never writes any *reason* supporting her claims. It's only a bunch of claims (well, really the same claim, always) without any attempt of proof.

And I'll not feed the troll anymore.

Posted by: Antonio at May 30th, 2016 5:51 PM

Michael:
Thanks. It does seem like no one here likes criticism or skepticism. There is too much wide-eyed optimism and expectations are way too high. People should temper their expectations with realism. Most scientists do not think we are close to extending our lifespans by any significant amount, nor do they think we are close to extending so-called "healthspans". Every time I read about some new "breakthrough" in regenerative medicine, stem cells, gene therapy, etc., there are always experts picking it apart until nothing is left. There are always caveats to every headline. If you take the headlines at face value, then perhaps it is easy to believe that we'll have anti-aging treatments by 2030. But if you dig below the surface, it becomes clear that even the first modest treatments will not be available before 2050, and that's being optimistic.

Posted by: MissKaioshin at May 30th, 2016 9:26 PM

"If we are to make real progress toward our goals, we need to be able to engage respectfully with reasonable critique from the wider public"

No. No, you really don't.

Sometimes I genuinely wonder if you know the first thing about human psychology. Don't you have any idea how the Moon landings were done? Practically everybody was saying it was impossible, but because we had national hope back then, they convinced people that they could do it, used the woefully underdeveloped technology of the late 60s, and got there anyway. Except now Neil's dead and Buzz is going to go the same way because nobody knows how to clear the amyloids and glucosepane from his system.

And are you seriously talking about cult-like thinking while Aubrey de Grey's still on the guest list of an "anti-aging" convention sponsored by, and chock full of, known quacks?

You have a functional framework to stop people from dying of old age. It either can work or it can't, if it can't work then this whole business really is a cult, and if it can work you need to start acting like it, holding the opinions of people actually doing the work to get this done higher than the opinions of people who don't know anything about it.

This kind of thing is why right-wingers use the term "cuck" - you've held the opinions, desires, and beliefs of people who oppose you more highly than your own. That's intellectual cuckoldry in a nutshell.

That isn't how you promote a charitable organization to get donations, Mike. Can you imagine if Susan B. Komen, Autism Speaks, or, hell, any other non-profit in the world took that kind of attitude? "We need to have reasonable discussion with people who will never believe that what we're doing is possible until we've already done it."

Of course there's going to be hefty setbacks, challenges, and problems, everything always takes longer and costs more, but you can't convince people to give their money to overcome these challenges if you make them believe that they're insurmountable within their lifetimes. Recruiting researchers is the same thing. What college student is going to get involved in anti-aging research if that person isn't convinced that he won't be completely wasting his time?

And even here everyone's completely forgotten the elephant in the room, which is that if we have no access to something that can lengthen our lifetimes WE ARE ALL FUCKING DEAD. So there's no point whatsoever in acknowledging "you can't do it any time soon" - if you can't, at least you died trying.

Posted by: Slicer at June 2nd, 2016 11:27 AM

@Slicer,Well said.

If we don't have hope for trying to get something done, why bother.
MissKaioshin takes a lot of positive energy from people. I really believe she loves doing that and getting a reaction from it. Reading her comments over the year, I would hate to be working with her or related to her. The old saying goes, if you can't say something nice, don't say anything. I guess she did not get the memo.

Posted by: Robert Church at June 2nd, 2016 8:45 PM

Less than a year ago I was in my 18th year of type2 diabetes. I weighed 224 lbs, with a height
of about 6'1.5" My hbA1C was 7.9. Now, thanks to extended release Metformin, taken along with
several substances that seem to greatly enhance the effect of Metformin, I am dramatically healthier & look much younger, than my 75.5 chronological age. These substances are Ptero-pure
developed by scientists with the USDA, working at the Pharma lab at the University of MS. A
scientist for the USDA, Agnes Mirando, is actually listed as inventor on the patent, which is issued to the U.S.government, itself. Pterostilbene, is the less powerful organic version of
the substance. In most respects it is similar to another fruit based sertuin substance,which
is quite well known, Resveratrol. A small group of Vets, that must use Metformin have joined
in the test efforts. Another substance, Quercetin, a well known apple sourced medicinal, which
working together in tandam, were tested with short lived lab rats at Mayo Clinic,& the Scrips
Inst. of Medical Research, in Jupiter FL. The rats live dramatically longer. It seems that the
research shows that this anti-oxidant, fruit substance, helps the body to rid itself of very
nasty senescent cells, which are found in the endotheliam of mammalian arteries...which includes those in human mammals. Now for 6 months I have been thriving at 177 lbs. on average.
My blood sugar is in the mid 5s! Blood pressure is basically optimum, as is cholesterol. Rosacea has disappeared on my cheeks. I have been able to do 600 curls daily with a 10 lb. hand
weight. I expect to have carotid artery endarterectomy on my left pair of carotids within a month or two, that will help ward off future stroke. I had my vision greatly improved by laser
surgery, which greatly improved my sense of wellness. I expect to live another 20 to 30 years
longer in good health if medical progress continues to advance. That will allow me, perhaps to
see age 100 or a little beyond. Millions of people could do the same, as these meds & medicinals are DIRT CHEAP...& our little band of VA enrolees have already helped to show the way. I hope at least a few of those reading this will read what is said about these effective
PRESENT DAY anti-aging options for longer "health-span"!

Posted by: Allan Silliphant at September 21st, 2016 2:42 AM

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