The Wealthy are Just Like the Rest of Us in that Many Want to Do Good in the World
The public echo chamber is often crowded by class warfare sentiments, and they are rarely absent from any discussion of progress in medicine. The green-eyed monster of jealousy dons its best suit and those without power denounce those who have more of it because of their greater wealth. Many believe that the wealthy have greater access to medical technology, while the truth is that those who complain, sitting in the first world, are in exactly the same tier as their wealthier counterparts, with access to exactly the same forms of medicine. The yawning gulf is that which exists between the complainants and the genuine poor in the third world, while the only thing that being first world wealthy buys you is a more handsome, well-dressed set of doctors than the average American will see. Under the hood the drugs are the same, the heart surgery the same, the cancer treatments the same, the outcomes the same. We are all aging to death, and the demographic studies tell us that massive wealth doesn't buy you all that much of an advantage at all.
That is unless the wealthy choose to spend that massive wealth on research and development, the production of entirely new capabilities in medicine. In which case they and everyone else might win together - provided the right research programs are funded. The wealthy who choose to fund medicine with the goal of extended health longevity are, with only a few exceptions, doing it not for their own benefit for but the population as a whole. Most of them believe that they will not live long enough to enjoy more than the first tentative results, as they are either not aware of the potential of SENS-like rejuvenation research programs if fully funded, or not yet convinced by those who advocate that work.
A truly wealthy individual is primarily a figurehead for a process, a life consumed by the demands of maintaining a vast amount of property and business interests. He or she cannot also be a citizen scientist, taking the years to become knowledgeable enough to make their own call about what is the best path forward in research. These high net worth individuals are each the leader of a tribe, beholden to advisers and interests, insulated from views and truth by a layer of people regardless of their desires on that front, and with many ongoing responsibilities that have little to do with philanthropy. Almost all philanthropists in the modern mold of successful businessmen are philanthropists in their snatched spare time, a minute here and a minute there taken hastily around the edges of the all-consuming job of steering their ventures. The exceptions are rare and usually older, retired, focused on spending down their fortunes to get things done: Paul Allen, Bill Gates, Paul Glenn, for example.
The class war voices would have us believe that the evil modern rich have turned to selfishly building longevity technologies for their own use, and to hell with the result of the world. That is simply untrue, not to mention impossible. It takes thousands of people, an entire industry, to build any entirely new class of medical technology. No-one can keep that to themselves: there are no secrets in business and science, and competitors always arise close on the heels of success. Further, the rejuvenation therapies of tomorrow will be infusions, mass-produced, and cheap as today's immune-altering biologics, taken every few years at a cost that after the first few years will settle to a couple of thousand dollars a shot or thereabouts if today's medicines are any guide. A few decades after that and these will be cheap enough for the third world, one step removed from free, like the simpler medicines of past years are today. In the matter of treating aging as a medical condition, we all win together or we all lose together. This is a collaborative game, not a competitive one.
Given this why do we not see the world's wealthy falling over themselves to change the world? Not just in the way we care about, to eliminate aging, but in general? I think it is that many simply do not know how to even begin to do this. Wealth doesn't grant vision, and becoming wealthy only gives you experience in managing your particular process for becoming wealthy. Most people don't look beyond their immediate surroundings, don't think far to the future, and that is just as true of high net worth individuals as it is of the rest of us. They have followed their particular passion, whatever it was that happened - as a side-effect - to mint money. That doesn't give a person any particular insight into how to use that money to change the world for the better. Look at the number of wealthy individuals who go into politics, for example. That is the ultimate public declaration of a lack of vision: it is an admission that you have no ideas on to how to change the world; you can see no further than ordering people around and rearranging the deck chairs that exist today.
So don't snipe at those who are actually trying to use their wealth to make the world a better place. They're figuring it out as they go along, just the same as everyone else has to, new entrants to areas of interest such as aging research and human longevity. Remember when you were first learning about this field of science and the present state of research? A wealthy individual will have just the same issues as you did; it's no easier for them to figure things out. The best that we can do is to help make the signposts better, more clear, and put forward sensible position statements on how newcomers can help to make a revolutionary difference in this field. (Such as by funding SENS research). This is just the same as we'd do for everyone else, as, after all, we're all in this together.
Why are all the tech billionaires chasing 'immortality'?
Although undoubtedly motivated by financial reward, for some investors who have proclaimed their wish to radically extend human lifespan there are also personal factors which can explain each individual's contributions. In this regard, those investing in radical life extension of course want to see the benefits of it themselves. But is it so hard to believe that billionaires really seek to do good with their money? Perhaps these investments can actually be explained as a desire to genuinely improve society by leading the cause of prolonging healthy lifespan.When Page and Brin formed Calico Labs, Missy Krasner, a Google Health employee declared: "Larry and Sergey have always had this grand vision about how to help society and improve public health." For Sergey Brin this mission has so far manifested itself in over $150 million of personal investments, given primarily to companies that use data to understand DNA. Together with Mark Zuckerberg, he also co-sponsors the $33 million Breakthrough Prize for Life Sciences, awarded to scientists engaged in curing age-related diseases.
Peter Thiel is also driven by the desire to improve public health in the US, a system which he is openly critical of, and one which is increasingly burdened by an aging population. In a Reddit AMA Peter Thiel declared: "We would never design a system like this if we were to start from scratch." As a result, through his $2 billion capital Founders Fund, Thiel regularly provides money for biotechnology companies and researchers looking at different ways to slow down or stop aging. He has provided Aubrey de Grey's SENS Research Foundation with over $6 million to help with their mission to find drugs to cure age-related damage.
Similarly Bill Maris has long insisted on a more meaningful purpose for Google Ventures' investments, and moving into the field of healthcare represents a chance for Google money to be used towards developing a more optimistic scenario where people are given the chance to live longer healthier lives. In exclaiming "medicine needs to come out of the dark ages", he plans to use Google Ventures as a primary vehicle for making this happen.
For the newest tech billionaire to enter the arena, Facebook's Mark Zuckerberg the intentions particularly appear to be altruistic and humanitarian. To Stephen Hawking's question in a recent Facebook Q&A on which of the biggest mysteries in science he would like to have an answer to, Zuckerberg wrote an entire list, including "how to cure all diseases" and "what could enable us to live forever?" Also, in 2013, in a status update, the Facebook chief executive wrote: "Our society needs more heroes who are scientists, researchers, and engineers," and "we need to celebrate and reward the people who cure diseases, expand our understanding of humanity, and work to improve people's lives."
Thus, judging by the amounts of money and time these investors are devoting to supporting a range of innovations designed to improve both the human condition and healthcare, one can easily determine that there is genuine interest in making a positive impact on society.
I've always thought it strange that Elon Musk hasn't, as far as I am aware, come out in support of radical life extension. I would have thought that he would be an ideal candidate to get behind it.
@Link: Musk is more interested in climate change, it seems.
"As a result, through his $2 billion capital Founders Fund, Thiel regularly provides money for biotechnology companies and researchers looking at different ways to slow down or stop aging. He has provided Aubrey de Grey's SENS Research Foundation with over $6 million to help with their mission to find drugs to cure age-related damage."
This shocks me. Only 6 million out of 2 billion? Why? Surely he knows SENS well, since he funded it. So, what's the problem? Does he think SENS is unrealistic? Why? Surely he knows that 1-2 billion will suffice for robust mouse rejuvenation, so why so small funding? What medical research can be more important than defeating aging?
@Antonio - I think Peter Thiel is still hedging his bets somewhat. He is willing to give a small amount to very high risk long term research bets such as SENS. If they can produce some solid technological demonstrations in mice then I'd imagine more money will be forthcoming.
It might be like powered flight, no one really believes in it until the first demo has been produced.
Do you know why he perceives SENS as very high risk and long term? I think usual gerontology research is much more long term and has less probability of success.
@Antonio how so? An example of more usual gerontology such as the work of Michael and Irina Conboy at UCB has had some excellent progress in tissue regeneration. Having spoken to Irina on a few occasions they believe they are ~5 years from having practical regenerative medicine passed phase one clinical. Demonstrated regeneration of tissue in rodent models as well as in human tissue via transgenic mice and in-vitro. You would think given their very recent demonstration of rejuvenation of brain and muscle people would be falling over themselves to fund and speed up that work. They are not, so what is really going on here?
@Steve H:
It's much longer term because it involves understanding how metabolism functions and how to safely and efficiently modify it to slow aging. This task is so hugely complex that it will take centuries, not the decade of RMR if properly funded.
Conboy's work is hugely ineffective compared to a working first generation set of SENS therapies.
Obtaining RMR with the usual approach of messing with methabolism to gently slow aging is thus much longer term and more risky than SENS approach.
Why not simply using half of the fund to fund SENS and see what happens in ten years?
It's annoying to wait. I really wanna shake up one of these billionaires. "How do you expect to use all those billions once you fall to pieces and die".
They are all waiting for someone else I guess. What a pity.
The entire idea that the human body can be repaired exogenously seems alien to most of everyone. The Chinese government should be interested in a nice and simple way to fix all those pollution-riddled Chinese lungs for instance. It ought to be cheaper to develop some Mitochondrion-repair techniques than to refit their entire society to pollute less.
@Antonio how can you compare the Conboy work which has been demonstrated with a first generation of SENS therapies? This set of therapies do not exist so how are you making such a comparison or is that a guess? You cannot compare the merits of a proven therapy against something that may or may not happen in ten years time, that is not scientific. I could just as easily say blue crystals are better at curing Cancer than currently available drugs but unless I have the data there can be no comparison.
Granted some aspects of SENS will no doubt be very useful IF they can be made to work, but we cannot compare the merits of one approach vs another if one technique is not at a stage where a meaningful comparison can be made and may not be so for ten years and only in mice.
Also I have to say that the Conboy work is not aimed at slowing aging it is aimed at direct regeneration of cells, tissue and organs by repairing the stem cells and restoring youthful gene expression profile and restoring replicative and regenerative potential. This is not the usual CR bandwagon aimed at modestly slowing aging they are addressing functional decline in what they see as the most direct manner.
Also Antonio Irina is talking about having a practical version of her regenerative therapy that is effective without a doubt in completed phase 1 clinicals in ~5 years. We are not talking about mice either this is in people.
Within 10-20 years time I really hope we see at least senescent cell removal in humans as far as the SENS therapies go. That would probably be useful in conjunction with something like Irina Conboys treatment, if that gets brought to market.
Steve H said:
"I could just as easily say blue crystals are better at curing Cancer than currently available drugs but unless I have the data there can be no comparison."
Not at all. Blue crystals prediction is supported by nothing, but SENS is supported by our current knowledge of physiology, pathology and gerontology. The fact that the therapies aren't available yet doesn't put them on the same foot than snake oil. We know the causes of atherosclerosis, sarcopenia, etc. and there are good reasons to think that they will be cured by SENS-type therapies.
If therapies worthiness could only be compared when completed, then medical research funding would be totally impossible.
AFAIK, Conboy's research is based on altering blood levels of substances that control stem cells level of activity, so that they work harder to do their function. These therapies don't repair the damage, only make a damaged machinery work harder, but damage is still there and it's still accumulating. Convoy's approach is not a rejuvenation therapy but a slowing aging therapy.
By simple logic, a therapy that eliminates damage must have a much larger effect on life expectancy than this one.
As for risk, I was comparing the risk of ten years of SENS to obtain RMR to the risk of the metabolism approach to obtain RMR. I was not comparing therapies with different goals (tiny increase in longevity vs. RMR).
If biology was that logical why do so many trials fail? There may be aspects of aging that are programmed and can be reverted.
IMO damage repair is probably the right way but don't be so sure.
During an AMA Bill Gates was asked about Calico and life-extension, and replied:
"seems pretty egocentric while we still have malaria and TB for rich people to fund things so they can live longer. It would be nice to live longer though I admit."
Would he say the same about putting billions of dollars into entertainment (doesn't Microsoft fund and publish very expensive AAA video games?) or spending much time and energy on romance and sex and nice tasting foods etc? None of this helps with third world malaria. Isn't life-extension with everything that implies (no alzheimers etc) actually a more worthy and worthwhile goal than creating another huge Hollywood blockbuster and many other things that seem uncontroversial and unproblematic to most. Not that I'm against those, but as a comparison to gain some perspective. If you're going jump on anything as "egocentric" don't let it be life-extension. Besides, ultimately it will likely benefit the entire world even if it will arrive earlier at some places.
@Antonio
"AFAIK, Conboy's research is based on altering blood levels of substances that control stem cells level of activity, so that they work harder to do their function. These therapies don't repair the damage, only make a damaged machinery work harder, but damage is still there and it's still accumulating. Convoy's approach is not a rejuvenation therapy but a slowing aging therapy."
I do not agree with this. Irina has reported that rejuvenated stem cells repair DNA double strand breaks and are almost as good as young stem cells (her own words) as well as enabling the repair pathways that enable them to repair adjacent tissues restoring function. This in turn helps restore a more youthful gene expression profile improving not only regenerative capacity as well as replicative potential but also addresses to a certain level genomic stability. So no it is not simply slowing aging but is in fact regenerative in nature. There is no reason why an approach such as the Conboys propose can be applied systemically as part of an overall repair stratergy. This idea that it is forcing damaged cells back to work comes up from time to time and is something that Irina has demonstrated to be untrue.
"Not at all. Blue crystals prediction is supported by nothing, but SENS is supported by our current knowledge of physiology, pathology and gerontology. The fact that the therapies aren't available yet doesn't put them on the same foot than snake oil. We know the causes of atherosclerosis, sarcopenia, etc. and there are good reasons to think that they will be cured by SENS-type therapies."
I am not suggesting SENS is snake oil, not at all. A fair amount of the theory is based as you suggest on current knowledge. I have no doubt if such therapies could be developed they would be very useful. However you originally compared Conboys regenerative approach with SENS which as I have pointed out is not possible, you cannot compare efficiency or efficiency of one therapy with another if one exists and the other does not yet exist in a state where a direct comparison can be made. When SENS has something that rejuvenates tissue then we can compare and choose the best option.
"By simple logic, a therapy that eliminates damage must have a much larger effect on life expectancy than this one."
Yes that logic is correct and by that metric stem cells returning to working order with repaired double strand breaks and improved gene profile and improved regenerative capacity by your definition would effect life expectancy. The Conboy approach has demonstrated numerous times in various tissues that repair of "some damage types" is occurring, why are you choosing to ignore or sidestep rather than acknowledge that some level of repair is happening here? Note: I am not suggesting it clears all damage eg, accumulated plaques etc... so these will continue to build up and need dealing with.
"As for risk, I was comparing the risk of ten years of SENS to obtain RMR to the risk of the metabolism approach to obtain RMR. I was not comparing therapies with different goals (tiny increase in longevity vs. RMR)."
Once again the goal of Irina and Michael Conboy is regeneration of tissue and organs not a tiny increase in longevity. If they applied their technique to every organ in your body and returned them to youthful function what basis do you have to support that it would only give a small increase in lifespan?
There are also many types of metabolism approach from things certain to achieve little eg, NAD+, Resveratrol etc... these are downstream effects of things happening upstream. The Conboys are going as far upstream as possible to an intervention point and addressing the cascade at that earlier point rather than getting bogged down in the complexity of downstream consquences. All metabolic approaches are not made equal.
Thank you for the discussion so far btw it has been genuinely interesting. Also if you have not seen this worth checking out:
https://www.youtube.com/watch?v=2IGpJTobI3k
and their latest paper:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494916/
You will note they mention B2M levels being reduced to near youthful levels when they inhibit TGF-b1 for a duration thus resetting both expression levels to an earlier state. B2M is also confirmed to contribute to aging as this follow on related study at TWC lab confirms:
http://news.sciencemag.org/biology/2015/07/old-age-protein-may-cause-memory-loss
B2M contributes to inhition of neurogenesis and Myogensis and cognitive decline.
@Arren: Since metabolism is so complex, drugs that modify metabolism are much prone to fail than drugs that don't.
Except that the Conboys have so far demonstrated a suitable intervention point which shares a common single targeted pathway that leads to rejuvenation. Brain, muscle, bone and skin all so far respond the same way to this single pathway. Irina believes it could be fairly generic as they are targetting metabolism far upstream at an intervention point.
@Northus:
Even the Malaria-TB vs. aging comparison is crazy non-sense. Aging is responsible for 2/3 of worldwide deaths, while malaria and TB together causes a mere 5%.
Steve H said:
"Irina has reported that rejuvenated stem cells repair DNA double strand breaks and are almost as good as young stem cells (her own words)"
This is repair of new damage (that is, slowing of damage accumulation), not repair of already present damage.
"as well as enabling the repair pathways that enable them to repair adjacent tissues restoring function"
This is true tissue repair, but there are still lots of molecular and cellular damage not repaired by this and, more to the point, it's repaired by forcing a still damaged machinery (stem cells).
"This in turn helps restore a more youthful gene expression profile improving not only regenerative capacity as well as replicative potential but also addresses to a certain level genomic stability."
According to SENS, DNA damage is not so important for aging, apart from its relation to cancer. I concede that this point is disputed by some researchers.
"So no it is not simply slowing aging but is in fact regenerative in nature."
This depends on the importance you concede to mutations/epimutations in aging (apart from cancer). If you think that aging is caused by damage, then this isn't repair/rejuvenation. If you think that aging is programmed, then it's. SENS researchers and the majority of gerontologists belong to the damage camp, while others belong to the programmed camp.
"ou cannot compare efficiency or efficiency of one therapy with another if one exists and the other does not yet exist in a state where a direct comparison can be made"
Of course I can and all funding organizations do that all the time. As I said, if they didn't medical research funding would be impossible.
"Once again the goal of Irina and Michael Conboy is regeneration of tissue and organs not a tiny increase in longevity."
But that is its probably outcome. Surely they didn't say that they will obtain something like RMR, it isn't?
Surely Conboy's research is far better than resveratrol and the like, but I think SENS is even far better.
I just like how everyone's arguing about Irina Conboy's approach being somehow a competitor to the SENS approach... when the Conboy lab has been funded by SENS and Irina's on the advisory board.
Anyway, I have to mostly agree with Reason's original post, but I do not find it credible that the founders of PayPal and Facebook do anything out of the goodness of their hearts; stick me firmly in the "they're doing this because they don't want themselves or their immediate family members to die, and if everyone else in the world survives, that's okay too" camp. Bill Gates opposes it, but he's been the Internet's whipping boy for two decades now; if he came out in favor, a huge chunk of people would be against, just because they hate him. Google, on the other hand, is run by transhumanists.
Still, the reasons why rich people fund this stuff are immaterial. Even if they wanted to keep it from other people indefinitely (what would be the point of that, again?), they can't. Forget morality for a moment; it'd be suicide if they tried, and every last one of them knows it.
People might do things because of altruism, ideology, or selfishness, but no one who functions in society ever does anything "for the evulz".
As far as the billionaires funding stuff... I'd like to see Larry Ellison get back into funding some research, given his past foundation and his vast amount of money. Wishful thinking I know, but still. Gates admitted it would be nice to live longer, I just think he feels like there are more pressing matters in the world. It would be great to see another big billionaire put their name behind SENS though. Would definitely catch more people's attention.
Sorry, I should have been more clear; I mentioned when he first made the comment that Gates' apparent public opposition is entirely because of PR matters. He can't divert money from his poverty funding to longevity, and he can't really make any statement that directly supports it beyond "it would be nice". Not now, anyway. It'd backfire, both on him and the idea as a whole. Too many people hate Gates, and too many people are paranoid of the whole "rich people want to keep it for themselves" thing.
I think the arguments against that are of five separate types: the moral, the financial, the social, the practical, and the consequential.
The moral: This is probably the weakest argument, but restricting access to longevity therapies is against the morality and ideologies of everyone involved in the business. Seriously, pick a name you recognize at SENS, Calico, the Buck Institute, anywhere; I guarantee that person will be opposed to restricting longevity therapies to any subset of people. Now, it could be that a few of these people are secretly uneasy with the idea of the world's worst, most useless, people also getting it, but they aren't dumb enough to say that out loud, because the overall morality is one of global access to longevity. (Expect the same with future transhumanization, most notably intelligence improvements.)
The financial: This is probably the stickiest part. "You won't be able to afford it" is a lot more credible than "It will be kept from you". People seeking wealth want to charge a lot of money for their products, especially to effectively captive audiences, and so overpriced drugs are a real problem. However, insurance companies will be a lot more willing to either negotiate those prices down or simply pay them anyway, because fixing problems in one shot is a hell of a lot cheaper (and easier to sell!) than prolonged end-of-life (also known as slow death) care. That's for private insurance; countries with socialized medical care don't charge their citizens. Similarly, the U.S. government, facing eleven-figure debts to the elderly, will find it much, much cheaper to keep these people out of nursing homes if it can't just eliminate the "elderly" category altogether. A lot of organizations offer assistance for people who can't afford lifesaving medical care, which is what this is. And prices always, inevitably, drop at some point, just as they have for everything else.
The social: People live in monkeyspheres, which intersect with other monkeyspheres, ad infinitum. Does the security guard's crippled mom get regenerative therapy for her aged spine? (Probably yes, you don't want to piss off your security people.) Okay, now this woman has a lot of friends her age who just watched her toss aside her wheelchair. Perhaps they have wheelchairs of their own they'd like to discard. She'll be asking him when they can get it, too, and it'll filter to his boss, who likely has a lot of other people suggesting to him that their friends, or their friends' friends, should get it at an affordable price. It's difficult to quantify the weight of this pressure, the power of literally everyone you know going "Listen, my mom's gonna die if she doesn't get..." SENS already has a lot of people going "uh, so yeah, when can I get fixed?" even though there aren't even any human treatments yet. Imagine the cacophony when there are! And then there's the clinicians whose patients can't afford it but need it to keep breathing.
The practical: Competitors have a wonderful habit of popping out of the woodwork once it's proven that a thing can be done. If your prices are too high, someone else does it for cheaper. You can't keep it a secret, and it's a hell of a job to prevent everyone, everywhere, from copying your techniques. The battle between generic manufacturers and patent holders is well-known, and that's for stuff that barely even works, let alone makes fundamental parts of people younger! (And, of course, a lot of these drugs will be fake, causing news headlines and a lot more screaming.) What happens if some large country just goes "Screw your patents" and institutes a national longevity program?
The consequential: Okay. Let's say that longevity treatments were, against all odds, somehow bought out and controlled by a cabal hell-bent on keeping them from the masses, charging tremendous amounts of money, refusing to listen to social appeals, and instituting global draconian patent protection to keep anyone else, even Eurosocialist countries, China, and Russia, from copying their techniques and making them available to the general public. What happens when literally everyone in the world is dying of old age, except for a few people who aren't? What might everyone do? Riots in the street would be the go-to approach, although it probably wouldn't even get that far; any candidate who ran on a "These people are getting indefinitely rejuvenated right now, vote for me and you won't rot to death" platform would sail to victory. If the democratic process failed to the point where that wouldn't be effective (and now we are firmly in implausible nightmare world), people might do literally anything in response. It's their lives at stake! All-out corporate hacking, robbery, hostage-taking, assassinations, outright terrorism of the splodey and shooty variety, you name it. A hotel maid, whose father died of curable Parkinson's, hands a door keycard to a man whose older brother died of curable atherosclerosis, and in a few minutes that maid has a lot more to clean up. A jaundiced gasoline truck driver, who's just been told that his insurance won't cover the really effective stuff for his pancreatic cancer, spies a Ferrari driven by a 60-year-old teenager on the other side of a double yellow. All he has to do is turn the wheel a little bit to the left. If you're trying to live forever, it's not a good idea to live in a world where everyone has a reason to kill you.
Steve H, SENS in the form of beta-amyloid vaccines is actually further along than any parabiosis research. Some of the vaccines are being tested in late-stage, human trials, and while they initially produced disappointing results, recent news has been more hopeful.
Slicer, the SRF is interested in parabiosis research to determine what underlying damage needs to be repaired in order to obtain the results seen in the parabiosis experiments without the potential side effects (see Michael's comment).
@Slicer:
I know that Conboy's research was funded by SRF. But that doesn't mean that it's part of SENS therapies. As Florian points out, they are funding it because it helps them to know where to focus SENS research on.
I agree with your opinion about billionaries.
And totally agree with your long post on why treatments will not be kept only for a few people.
Sorry, I meant Florin, not Florian.
Thanks for the info Florin about the plaque clearing technology that is very interesting!
Antonio, Florin: Yes, I know it's not complete repair by itself, but it's still a necessary component of successful stem cell therapy. One of the key findings of the Conboy lab is that even fresh stem cells stop working when exposed to an aged environment, and the blood factors that make up an aged environment (in skeletal muscle, anyway) are excreted by the same cells that they're trying to replace with fresh ones.
So any treatment involving stem cells has to directly intervene in this environment- otherwise it can't replace the cells it needs to replace to have a fresh environment! The only alternatives are to either directly modify the aged cells so that they stop producing these factors- a treatment that I'm sure Dr. Conboy would love to see- or kill off the aged cells before you replace them, which is a very inappropriate idea for, say, heart muscle.
Exactly Slicer!
Slicer, I don't see any problem with killing off the aged cells or repairing them. The aged cells you're referring to could be senescent cells or cells which have mutant mitos. Killing off senescent cells is unlikely to damage muscle, because these cells are rare even in old people, and AFAIK, aren't part of muscle fibers. The cells with the mutant mitos might be rescued by allotopic expression.
Slicer, check out this the comments on this thread... worth reading if you're going to partake in the AMA with Aubrey de Grey on the 4th like you mentioned. https://www.reddit.com/r/Futurology/comments/3f6thg/first_humans_to_live_to_150_already_alive/
I really have to agree with Aubrey when he says the term "immortal" is damaging. It gets thrown around here relentlessly, along with the usual "it'll be restricted for the rich only" and "our resources are strained, overpopulation" type comments. There are plenty of people out there who's opinions we need to hopefully change and get on our side. No one seems to actually think or realize that this will likely be a piecemeal approach. Everyone hears "longevity", and equates it with "immortality" and a magic pill. Ugh.
Sorry for posting this here, it's a busy comments section at the moment though. I wish we were able to PM or something.
I'm going to have to leave the relevant questions to the professionals, as the details determine what therapies can be done in what order.
Drs. de Grey, Conboy: If you're reading this, are the cells responsible for the aged environment in fact totally senescent, or are they still mostly functional? Is the blood factor problem caused by a substantial portion of the muscle cells, or is it caused by a few bad ones that can be identified and picked off without causing serious overall harm? Are these blood factors being caused by malfunctioning mitochondria or something else? Is it even remotely feasible to alter cells so that they stop producing these factors?
(I'm not really expecting answers to these questions, because I don't think they know them yet.)
Stepping in for Dr. de Grey:
Slicer wrote: are the cells responsible for the aged environment in fact totally senescent, or are they still mostly functional? Is the blood factor problem caused by a substantial portion of the muscle cells, or is it caused by a few bad ones that can be identified and picked off without causing serious overall harm? Are these blood factors being caused by malfunctioning mitochondria or something else? Is it even remotely feasible to alter cells so that they stop producing these factors?
You're right that we are very far from having a complete answer to this question. They are being caused by any number of different forms of aging damage to different cell types, each of which causes the cell to alter the signaling environment in different ways. Any time you damage a cell, you're likely to alter its output of signaling factors and its response to same; when you gradually accumulate cellular or molecular damage that doesn't resolve over time in aging tissues, you progressively distort the signaling environment. Hence, the aging body's signaling environment becomes progressively altered, both adaptively (to allow cells to carry on functioning in the near term in the face of damage) and, of course, maladaptively.
Two of these, where the effects on the signaling environment are particularly high-profile, are senescent cells and cells harboring mitochondria with deletion mutations in their genomes (so right there, you can see that some of the responsible cells are totally senescent, and some aren't "senescent" at all in the sense that the term "cellular senescence" is normally used). But, in the case of muscle, for instance, the signaling environment is also altered by foam cells in local atherosclerotic arteries; by differentiated muscle cells with intracellular β-amyloid accumulation (which is characteristic of aging muscle and linked to sporadic inclusion body myositis (sIBM); by the systemic effects of accumulation of excessive visceral adipose tissue macrophages; by adipocyte replacement or transdifferentiation in aging muscle; and doubtless any number of forms of damage whose role hasn't yet been uncovered, or of which I'm not thinking or aren't aware.
Agree with the above especially some senescent cells are not senescent at all. I have various papers showing that some senescent cells can be returned to working order via factoral signals.
Sliver I will speak to Irina and Michael and see what they have to say about your question. She recently said when they regnerated the cells they are almost as good as young cells and that the damage rapidly was gone, meaning either the cells were able to repair damage fast (circa 48 hours or so) or that the damage was not significant in the first place.
She was I believe talking about DNA damage eg double strand breaks and that is vindicated by a study I saw recently where senescent cells were recovered to full working order, strand breaks observed in these senescent cells were no longer evident when regenerated. Admittedly the paper I read was involving neonatal cells in-vitro but I believe something similar occurs with her work.
Anyway I will pose ask them about this as it is an interesting question, thanks to Michael for wading in for ADG too.
I am interested in the SENS work for foam cell clearance and I know of at least one other projects of a similar nature, cannot say more at this point in time unfortunately.
Slicer answer to your question from Irina Conboy:
"Any cell can and will repair DNA damage (more effectively, if such cell is dividing). We do not observe accumulation of DNA damage in muscle stem cells with age to begin with and the tissue which they make when activated by "young blood" or defined molecules, is as good as new, based on what we looked at (gene expression, epigenetics, regeneration). The cells of the aged tissues are not totally senescent and in fact, it is difficult to see the elevated p16 expression or SA-beta gal in most old tissues in live mammals; there are only small clusters of the "bad senescent" cells, based on current thought; and the work on their characterization and removal is in progress in Campisi lab. Based on our work, old cells, including the old muscle stem cells and old muscle fibers express more p16 mRNA and protein than young, but they can still be induced to divide and repair the tissue damage by defined molecular cues in hours to days with p16 levels going down to "youthful" (e.g. they are not "spoiled" irreversibly)."
Hope you like this information.
Slicer it's your lucky day. Michael Conboy jumps in and says:
>There is a discussion on fight aging about signals and senescent cells and your work is being discussed as the main focus. >Someone has asked Aubrey de Grey and you the following question:
>"Are the cells responsible for the aged environment in fact totally senescent, or are they still mostly functional?
Irina got that one, still mostly functional.
>Is the blood factor problem caused by a substantial portion of the muscle cells, or is it caused by a few bad ones that can be >identified and picked off without causing serious overall harm?
I don't think the "blood factor problem" is caused by muscle cells, at least not specifically. One could argue from in-vivo data alone that it is because of "bad platelets" (with more inflammatory cytokines), but they can't be all to blame either.
>Are these blood factors being caused by malfunctioning mitochondria or something else? Is it even remotely feasible to alter >cells so that they stop producing these factors?"
So that's the real question. In general, I see the circulatory millieu changing to something more differentiation-signaling and inflammation-signaling, with odd changes indicating increasing dysregulation. The stem cells in tissues become less prone to proliferate, and thus maintain/repair/regenerate tissues. The tissue cells become more dysregulated, including having malfunctioning organnelles, like those mitochondria. Which ones of those changes are chickens and which eggs, I don't know, maybe that's not the question.
>You mentioned you observed rapid regeneration of cells in your work (I think michael said in about 48 hours) and that the >damage rapidly repaired itself and that meant either the cell were able to quickly repair the damage or the damage was not >that significant to begin with. You have said to me that regenerated cells are almost as good as young ones (certainly the case as the gene expression changes prove)
Yes, they have to be "rejuvenated" to respond to muscle injury within a day or so by the various interventions or we wouldn't see the molecular and cellular restoration to young levels by the time we do (1-3 days depending on what we look at) . Now that might also be because if they weren't boosted in a day or so, the muscle wouldn't regenerate well and we'd have put that intervention in the "didn't work" pile, which doesn't always get published (and often forgotten...)
>but what about mtDNA damage, have you observed any reversal of damage to them?
So we have some data (about $100K away from being published), that a postdoc worked up in the lab showing that gross mitochondrial function of old muscle regenerative cells was restored by some of the things we do to restore old muscle cell function. Whether that means the cells with the bad mitoes die, repair their mitoes, autophagocytose them to make room for the good mitoes or whatever, we don't know.
I keep coming back to the theory that if we could just keep growing a little, or somehow replace or regenerate tissue, we'd get ahead of the dysregulation, inflammation, accumulation of junk (mitochondria, plaques, whatever). The problem seems bigger and more chaotic than one process, like only telomeres or mitochondria, although studying those have been super informative.
More researchers should make a habit of presenting financial matters relating to research in the form of "about $100K away from being published".
What you think of the work so far then Reason? 100k seems so trivial for some really important answers IMO
Fusion researchers say something similar:
[quote]
When will fusion power my house (or vehicle)?
MIT Researchers: This is obviously an impossible question to answer, but we can give some thoughts about when it might happen, and why. First, the current official plan is that ITER will demonstrate net fusion gain (Q = 10, that is, ten times more fusion power out than heating power put in) in about 2028 or 2029. (Construction will be done by about 2022 but there’s a six-year shakedown process of steadily increasing the power and learning how to run the machine before the full-power fusion shots.) At that point, designs can begin for a “DEMO”, which is the fusion community’s term for a demonstration power plant. That would come online around 2040 (and would putt watts on the grid, although probably at an economic loss at first), and would be followed by (profitable, economic) commercial plants around 2050.
This seems like a long time, and it is, but it’s important to understand that this is not the only possible path. You might say that we’re not a certain number of years away from a working fusion power plant, but rather about $80-billion away (in worldwide funding). We’ll get into this more in response to one of the other questions, but there are other experiments that could be done in parallel with ITER that would certainly speed up the goal of a demonstration power plant, if there were the money for it.
[/quote]
http://slashdot.org/story/167399
I too like this form of addresing funding.
BTW, very interesting information, Steve.
Talking to Michael I said 100k seems such a trivial amount to answer important questions and he said something I think it quite interesting and a possible idea for community fund raising:
"Donor-sponsored projects might actually be more productive, and much less of a waste of time, than what were currently enjoying with the NIH unfunding model! To get this kind of project rolling in our lab means getting a new person on the project who's not obligated to the existing funding committments. I've attached some numbers from recent budgets that we've submitted, where a postdoc costs around $100K per year for salary, supplies, etc., (IMO, postdocs have the highest ratio of productivity to costs compared with students or most senior researchers).
The discussions I've had with well-educated, non-scientist, anti-aging enthusiasts makes me think many donors would get a kick out of planning and cultivating their "pet" project. They would learn a lot (especially to see how ideas and plans adapt into something defensible, when challenged by a room full of academics), and have the satisfaction of personally turning the scientific wheels a notch, and we'd get the funding to do what is our passion. "
I think the work they do is very valuable and they seem to feel they are not that far from having regenerative medicine in clinical trials ~5 years. Probably sooner with more support. Question is can we do anything to help them?