Aubrey de Grey Speaks on Several Longevity Topics

[Dean Pomerleau]

Here is a new 20min video interview of Aubrey de Grey on Youtube in which he covers some interesting topics, including:

• The self-experimentation Liz Parrish from Bioviva has done to modify expression of genes telomerase & for preventing sarcopenia.
  • Aubrey says there some evidence these modifications could be beneficial.
  • But both have their potential downsides as well (e.g. cancer for telomerase).
  • He admires Parrish for her boldness, and for bringing the possibility of genetic manipulation in humans for health / longevity to the public debate.
  • But he worries that it will be very difficult to identify any measureable benefits that might result from these interventions, since Parrish is young and healthy
• The newly FDA-approved study of metaformin as a potential anti-aging drug.
  • He is skeptical of CR mimetics like metaformin, due to his skepticism that CR will have much longevity benefit in long-lived species.
  • He applauds the effort to study aging as a disease that can be treated, as this study attempts.
• CRISPR-cas9 gene editing technology
  • He sees lots of potential for this technology to facilitate the kind of health / longevity interventions his SENS Foundation is investigating
  • He doesn't see a lot of benefits/advantages (yet) for using the other recently publicized DNA technology, DNA_Origami, for drug delivery relative to other drug delivery methods.

--Dean

[Dean Pomerleau]

All,

 

Here is a new 30-min audio interview with Aubrey by one of the leaders at Longecity.org.

 

As you might expect given the source of the questions (i.e. longecity.org members) this isn't Aubrey's typical 'stump speech' on anti-aging. It is quite informative. The podcast starts out with some very good detail about how 3 different SENS research strands have progressed over the past decade - getting rid of oxidized cholesterol (very good progress) eliminating the intracellular gunk associated with macular degeneration (pretty good progress) and extracellular crosslinks (can now synthesize the crosslinked compound in the lab so experiments like what they've done with oxidized cholesterol can finally begin in earnest).

 

He estimates with the proper funding (i.e. a lot more than today) successful mouse rejuvenation could happen in 6-8 years, but with current level of funding it will likely take 15 years. As for human trials, the progress they are making to break down oxidized cholesterol or eliminate the macular degeneration gunk will probably take "15 years if we're lucky".

 

The last 10 minutes deal with funding and "politics" of aging research. Some good commentary about Calico (they've pretty much blown off collaboration overtures from SENS Foundation) and the NIA/NIH (still not much progress on joint funding of projects by NIA and diseases-of-aging-focused agencies like National Cancer Institute due to politics). 

 

So unfortunately, but not surprisingly, the fight to defeat aging in humans appears to be at least several decades away, unless things change massively in the funding & political landscape.

 

Michael, here is something I've wondered about and perhaps you can answer. In the SENS engineering approach to defeating aging, the strategy is to target specific pathways by which aging-associated damage occurs, like the accumulation of intra- or extra-cellular gunk. Do you guys have a ballpark estimate of how many different specific gunk compounds there are that would each need to be targeted individually, like you are doing with 7-ketocholesterol, in order to conquer aging? Are there just a few, tens, hundreds or thousands that will need to be dealt with before we get a handle on postponing/curing the diseases of aging? It would seem to make a big difference wrt to the tractability, not to mention the timeframe, of the SENS approach.

 

On a related note - in this answer on Quora.com to a question about the "low hanging fruit" of anti-aging research, Aubrey says:

 

If we go with the seven categories, probably the one we call "intracellular waste products" would be first [i.e. lowest hanging fruit] because it drives the #1 killer in the Western world, atherosclerosis. However, even then we would only expect a few years. To get more than about 15 years we'd definitely need to have at least reasonably effective repair of all seven categories (the sole potential exception being mitochondrial mutations because we don't yet know for sure what pathologies they drive and how powerfully).

 

Having "reasonably effective repair of all seven categories" (and thereby achieving longevity 'escape velocity') which are not only implemented in vitro or animals, but tested on humans and FDA-approved, sounds like a pretty daunting task. But as Aubrey always emphasizes (except perhaps to rich potential donors  ), he's in this for the long haul, not necessarily to help himself or adults alive today, but to help future people, or perhaps young people alive today...

 

--Dean

[Zeta]

So unfortunately, but not surprisingly, the fight [success of the fight, you mean, not, I assume, the time when it commences in a far more serious way than it has already has - Zeta] to defeat aging in humans appears to be at least several decades away, unless things change massively in the funding & political landscape.

 

Dean, thanks for the link/tip.

 

Whence your "so" here, about "at least several decades"? Not sure that follows from the foregoing, nor even that "appears to be according to Aubrey..." follows. I'm not sure how much you're taking Aubrey's comments about Calico to be relevant to the timing of anti-aging fights and successes, but, personally, I think Calico and other huge, for-profit efforts started being started by rich "nouveau longevists" might succeed dramatically very soon. The resources that are being put into intervening in aging are skyrocketing, and I see no reason for that to change.

 

Zeta

[Dean Pomerleau]

 

Zeta,

 

Whence your "so" here, about "at least several decades"? Not sure that follows from the foregoing, nor even that "appears to be according to Aubrey..." follows. I'm not sure how much you're taking Aubrey's comments about Calico to be relevant to the timing of anti-aging fights and successes, but, personally, I think Calico and other huge, for-profit efforts started being started by rich "nouveau longevists" might succeed dramatically very soon. The resources that are being put into intervening in aging are skyrocketing, and I see no reason for that to change.

 

My perspective on how far away we are from appreciable, deployable solutions to human aging (at least several decades), is based on statements from Aubrey, who I respect greatly in this regard. If anyone has a realistic perspective on what its going to take to beat aging, I think it is Aubrey. Here is what he has said:

1. Clearing extracellular junk is the 'low hanging fruit' among the seven contributors of aging he's identified.
2. Human trials (or perhaps human deployment) of the first of these junk clearing solutions (e.g. 7-ketocholesterol therapy via genetic engineering of human cells to eat the stuff) is "15 years out if we're lucky".
3. 7-ketocholesterol is just the first of who knows how many forms of extracellular junk that will need to be cleaned up to defeat aging - it is probably at least in the 10s, perhaps even 100s - the human metabolism seems crushingly complex and messy. (see image below of just a small part of it, which you can zoom in on here - panning around the details of this image can't help but fill one with awe, and makes me wonder how we avoid dropping dead on the spot - seriously...)
4. Extracellular junk is just one of the seven categories of causes of aging he and colleagues have identified.
5. We'll need "reasonably effective repair of all seven categories" to make dramatic gains in healthy lifespan (i.e. 15 years extra years of life).

I think it is pretty clear from this chain of statements that Aubrey thinks dramatic progress in defeating human aging is at least several decades away.

 

Regarding Calico - listen to 18:45 - 21:30 for the basis of Aubrey's skepticism. He says almost all of the money going into Calico is going into "short term stuff - big pharma deals to develop specific drugs that mights modestly postpone specific diseases of aging", which Aubrey says isn't going to get us very far towards defeating aging. As for the future-oriented stuff going on at Calico, the leadership is steering their effort towards "discovery-driven basic science", rather than an engineering approach building on what we already know. Aubrey says the leader of this effort at Calico is "on record as saying he doesn't have a translational bone in his body, which is disconcerting."

 

It seems from Aubrey's perspective, there isn't going to be a magic bullet (like some people think telomerase might be, or people used to think of calorie restriction) - i.e. a master switch that dramatically improves, to say nothing of actually solves, the aging problem. Instead, he thinks the approach that will work will require chipping away at the many metabolic pathways that eventually break down, cause damage, and result in (or are) aging.

 

I not naturally one who likes to rain on anyone's parade - I'm usually an optimist. But I'm just extrapolating from Aubrey's remarks that such a 'chipping away' effort is likely to be a long slog, just like it appears translating the human genome into actionable benefits for human health has become, after the initial euphoria of decoding the human genome wore off 10 years ago.

 

I'd love to hear Michael's take on SENS Foundation perspective on this stuff.

 

--Dean

 

[Zeta]

 

My perspective on how far away we are from appreciable, deployable solutions to human aging (at least several decades), is based on statements from Aubrey, who I respect greatly in this regard.

 

I love Aubrey's efforts, but, after starting out in a different field, he's now become an expert, and "experts tend to underpredict".

 

More importantly, there are plenty of other people working on anti-aging with a very different view of the challenges. I'm not convinced they're wrong and Aubrey's right.

 

Myself, I'd say that if a concerted effort to develop stemcell-based rejuvenation techniques were made, we could have organ-rejuvenation and -replacement by around the end of the 2020s, for every part of the body except the brain. The other six "sins" wouldn't be so relevant.

 

But, alas, they wouldn't be entirely irrelevant precisely because of the brain. That, of course, would completely negate an argument about stem cell-based therapies obviating the complete SENS approach. But it's a question to which I'd say we don't yet have answers. Clearly, injecting a bunch of stem cells into the brain won't do. (It won't do for other organs either!) But there's been lots of interesting work showing, for ex., that glial cells can be transformed into neurons, and, with enough effort, we can learn how to get them to integrate into the brain in such a way as to replace or reinforce networks of memory that otherwise would be dying out, so that identity is maintained. This would mean that at least a few of the seven elements of SENS could be ignored.

 

We're not there yet, but with a doubling or so of funding, I think a 1.5-2 decade time frame is not unrealistic. We need more people working on brain rejuvenation!

 

Zeta

[Dean Pomerleau]

Hi Zeta,

 

I respect your perspective on this, but believe Aubrey is one of the very few longevity researchers who is both focused on actually doing something about aging (as opposed to basic research) and who is not employing "smoke and mirrors" to make their approach seem more promising and comprehensive than it is likely to be. 

 

 

 

We're not there yet, but with a doubling or so of funding, I think a 1.5-2 decade time frame is not unrealistic.

 

I think it would take a lot more than doubling of funding, but I think it might be possible to make progress towards "longevity escape velocity", and buy us all perhaps another decade or so within 1.5 - 2 decades via a "Manhattan Project"-like effort to address aging. 

 

 

 

We need more people working on brain rejuvenation!

 

I agree the brain is perhaps the weakest link, or the biggest hurdle to indefinite lifespan extension. The big problem is that unlike all our other organs, brain scientists have very little idea about how the brain actually works. Heck, it was just discovered a couple months ago that the lymphatic system is connected to and likely contributes to brain health by clearing out junk that accumulates in the brain. Perhaps we can figure out how to preserve and rejuvenate it without such understanding, but I'm far from certain of this, and even a semi-complete understanding seems likely to take a long time, despite big programs like the federally-funded European Human Brain Project & US Human Brain Project, and efforts like the Allen Institute for Brain Science, led by one of my heros, Christof Koch. We're throwing a lot of money at brain research, and making progress, but its not clear at this point that even more money will result in faster progress.

 

On a related note here is an interesting new Quora.com answer from Aubrey relevant to both Calico and the question of replacement organs.

 

Question: Does SENS Research Foundation have plans to start collaborating with, or to collaborate more closely with Calico, Human Longevity Inc., and/or Alcor Life Extension Foundation?

 

Answer from Aubrey:

 

Calico: we hope so, but they have basically blown us off so far. They are being quite secretive about their plans, but from the range of people they are hiring they have not yet really got the message that damage repair is the way to go.

 

HLI: maybe, but the connection is less obvious there, because HLI are not (yet!) really in the business of defeating aging entirely; instead they are seeking to improve personalised medicine by sophisticated use of genomic sequence data.

 

Alcor: yes and no. I've been on their SAB for a decade but we don't work directly with them. However, their ex-CEO Tanya Jones, who was for five years our COO, is now CEO of a hugely exciting startup named Arigos (along with Steve Van Sickle, who preceded her as Alcor CEO) - they are working on a new method of cryopreservation that has huge near-term potential in the organ preservation market as well as being a potential game-changer in cryonics per se. We invested in Arigos when they set up.

 

--Dean

[Dean Pomerleau]

One other thing. Besides the problem of brain aging, Zeta you expressed optimism about the power of stem cell therapy to deal with (most) other causes of aging. Aubrey and Biomedical Gerontologist, Marios Kyriazis aren't quite so sanguine. Here is what they wrote in response to another Quora.com question on the potential longevity benefits fo stem cell therapy alone. 

 

 

 

These two answers, and particularly Marios analogy with repairing a city after a war involving not just the buildings but the linkages between them. I'll ask about it in my next post in this thread, to avoid trying to cram too much into one post.

 

--Dean

[Dean Pomerleau]

In the above Quora answer on why stem cell therapy isn't the holy grail for life extension, Mario Kyriazis says:

 

It is not just the individual elements (cells, proteins, genes, enzymes) that matter, but also the way these are connected between them and how they interact. 

 

This statement reminded me of this story about progress in aging research in 2015 that I read over the holiday and have been meaning to post/ask about. Since it relates to the SENS strategy, I'm hoping Michael might chose to answer, particularly since I'm serving as his conduit to fund the subversive web service Sci-hob.io (misspelling intentional and no last name mentioned, for the sake of Michael's extremely cautious nature). 

 

In the story, it talks about one source of aging that is receiving more attention lately, namely the breakdown of essential barriers, often in the form of necessary and important connections between cells. Here are a couple quotes:

 

Beyond the deterioration of proteins and DNA packaging, the body may age when essential barriers break down. 

 

Old stem cells in the brain had worn-out walls inside an organelle called the endoplasmic reticulum. These weakened walls let cellular junk seep back in during division, cutting down on the stem cells’ ability to produce new cells.

 

Another protective wall, the blood-brain barrier, might also waste away with time. Usually this barrier guards the brain from dangerous toxins in the blood. But MRI scans measuring barrier permeability in living human brains found that old people had leaky walls around the hippocampus, a structure involved in learning and memory.

 

And it pretty commonly accepted that permeability of the colon wall increases over time, especially with a bad diet, increasing systemic inflammation and therefore accelerates aging, not to mention leaky gut syndrome. Plus (obviously) permeability of artery walls to LDL cholesterol (particularly small, oxidized LDL cholesterol particles) is implicated in atherosclerosis [1].

 

So my question for Michael or anyone else with better insights into SENS way of categorizing damage than I have, is the following:

 

Which of the seven causes of aging SENS has identified (and is targeting with its research agenda) does this type of breakdown in important barriers  & linkages between cells fall? Here are the seven: 

1. Extracellular Junk
2. Intracellular Junk
3. Extracellular Crosslinks
4. Cell Loss and Atrophy
5. Death-Resistant Cells
6. Cancerous Cells
7. Mitochondrial Mutations

#3 or #4 seem like the most likely candidates, but it sounds to me like #3 is focused on preventing/reversing bad crosslinks (like glycation) rather than preserving/rejuvenating good linkages and connections between cells. #4 doesn't seem to quite fit either, although I guess this type of damage to barriers could be stretched to be classified as "atrophy". 

 

I know in the specific case of atherosclerosis, SENS is currently focused on clearing the bad gunk (i.e. 7-ketocholesterol) associated with the disease, that is downstream from the event of LDL leaking through artery walls. And in general, it seems that the SENS Foundation strategy is not to prevent changes that lead to the damage of aging, but instead to clean up the mess that results. By analogy, you can try to bail water out of a leaky boat, but when the holes get numerous or large enough, the task becomes hopeless.

 

In short, it seems at least to my naive understanding that the problem of "barrier breakdown" is a source of damage that may be slipping through the cracks of the SENS research strategy. (Yes - pun intended, heck, it was half the motivation for penning this post   ). And more generally, this type of damage seems like one more challenge that will make robust life extension difficult to achieve within the next couple decades.

 

--Dean

 

-----------------

[1] Atherosclerosis. 1996 Jun;123(1-2):1-15.

Transfer of low density lipoprotein into the arterial wall and risk of
atherosclerosis.

Nielsen LB(1).

Author information:
(1)Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen,
Denmark. Lars_Bo_Nielsen@quickmail.ucsf.edu

The aim of the review is to summarize the present knowledge on determinants of
transfer of low density lipoprotein (LDL) into the arterial wall, particularly in
relation to the risk of development of atherosclerosis. The flux of LDL into the
arterial wall (in moles of LDL per surface area per unit of time) has two major
determinants, i.e. the LDL concentration in plasma and the arterial wall
permeability. LDL enters the arterial wall as intact particles by vesicular
ferrying through endothelial cells and/or by passive sieving through pores in or
between endothelial cells. Estimates in vivo of the LDL permeability of a normal
arterial wall vary between 5 and 100 nl/cm2/h. In laboratory animals, the
regional variation in the arterial wall permeability predicts the pattern of
subsequent dietary induced atherosclerosis. Moreover, mechanical or immunological
injury of the arterial wall increases the LDL permeability and is accompanied by
accelerated development of experimental atherosclerosis. This supports the idea
that an increased permeability to LDL, like an increased plasma LDL
concentration, increases the risk of atherosclerosis. Hypertension, smoking,
genetic predisposition, atherosclerosis, and a small size of LDL may all increase
the arterial wall permeability to LDL and in this way increase the risk of
accelerated development of atherosclerosis. The hypothesis that atherosclerosis
risk can be reduced by improving the barrier function of the arterial wall
towards the entry of LDL remains to be investigated; agents which directly
modulate the LDL permeability of the arterial wall in vivo await identification.

PMID: 8782833

[Dean Pomerleau]

More on the topic of my last post in this thread - the importance for health and longevity of maintaining healthy barriers between compartments in the body. 

 

Al Pater posted this new paper [1] which discusses how methionine restriction (MR), a regime thought to mimic some aspects of CR and extend lifespan, at least in some organisms, leads to tighter junctions between epithelial cells, which is important for "proper function of all organs, including the lung, liver, gastrointestinal tract, reproductive tract, blood-brain barrier, and kidney." I bet CR may have the same effect, and maintaining such barriers may be part of the way CR benefits health and longevity in the animal models in which its been shown to work. 

 

As for mechanism, the authors say:

 

MR has been found to modify the protein composition of tight junctional complexes surrounding individual epithelial cells in a manner that renders the complexes less leaky.

 

Again I wonder which (if any) of the seven SENS remediation strategies would target the maintenance of these extra-cellular junctions, which serve as important barriers between bodily compartments.

 

--Dean

 

-----------

[1] Methionine restriction fundamentally supports health by tightening epithelial barriers.

Mullin JM, Skrovanek SM, Ramalingam A, DiGuilio KM, Valenzano MC.

Ann N Y Acad Sci. 2015 Dec 8. doi: 10.1111/nyas.12955. [Epub ahead of print]

PMID: 26646941

 

Abstract

 

Dietary methionine restriction (MR) has been found to affect one of the most primary tissue-level functions of an organism: the efficiency with which the epithelial linings of major organs separate the fluid compartments that they border. This process, epithelial barrier function, is basic for proper function of all organs, including the lung, liver, gastrointestinal tract, reproductive tract, blood-brain barrier, and kidney. Specifically, MR has been found to modify the protein composition of tight junctional complexes surrounding individual epithelial cells in a manner that renders the complexes less leaky. This has been observed in both a renal epithelial cell culture model and in gastrointestinal tissue. In both cases, MR increased the transepithelial electrical resistance across the epithelium, while decreasing passive leak of small nonelectrolytes. However, the specific target protein modifications involved were unique to each case. Overall, this provides an example of the primary level on which MR functions to modify, and improve, an organism.

 

KEYWORDS:

 

barrier function; claudin; methionine; occludin; tight junction; transepithelial

[Dean Pomerleau]

All,

 

Earlier in this thread, Zeta expressed what might be a healthy dose of skepticism about what he considers Aubrey's de Grey's pessimistic prognostications about how long it will take to reach longevity escape velocity (LEV):

 

My perspective on how far away we are from appreciable, deployable solutions to human aging (at least several decades), is based on statements from Aubrey, who I respect greatly in this regard.

 

I love Aubrey's efforts, but, after starting out in a different field, he's now become an expert, and "experts tend to underpredict".

 

More importantly, there are plenty of other people working on anti-aging with a very different view of the challenges. I'm not convinced they're wrong and Aubrey's right.

 

...

 

We're not there yet, but with a doubling or so of funding, I think a 1.5-2 decade time frame is not unrealistic. We need more people working on brain rejuvenation!

 

Here is what Aubrey said recently on Quora about the timeframe for reaching LEV: 

 

Q: How long will it take for anti-aging technology to reach escape velocity under current SENS funding?

 

A: Aubrey de Grey

 

That depends on how long one expects the funding to stay at current levels. At present I think we could be going roughly three times faster than we are if we had $50M per year to spend rather than only $5M. But as we make more progress, it will inevitably become easier to raise more funds. Taking all such things into account, I currently estimate that if we jumped to the $50M/year level tomorrow we would have a 50% chance of reaching LEV within 20-25 years, and every three years that go by with funding staying stagnant adds two years to that number.

 

So Aubrey estimates  50% chance of getting to LEV in 2 - 2.5 decades assuming SENS research suddenly gets 10x their current level of funding.

 

[Aubrey has] now become an expert, and "experts tend to underpredict".

 

Yes, Aubrey is an expert, but he's also (unhappily) a fundraiser and a politician, spending most of his time advocating for more support for research into anti-aging interventions. If anything, those are strong motivations to over-promise rather than under-predict. I consider his seemingly pessimistic timeline (from our personal perspective anyway) in the face of this strong temptation to sugar-coat the situation to garner more resources be refreshingly honest, and a sign that he's probably better calibrated than most in the anti-aging field. 

 

Further, it seems to me that most other researchers in the anti-aging field have yet to fully cognize (let alone factor in) the complexity of the aging process, instead focusing on single interventions like telomere lengthening, or stem cell therapy. I consider it nearly impossible to argue with Aubrey's observation that there are multiple distinct causal pathways in the aging process (seven by his count). While I'm not certain he's covered them all (see the two previous posts in this thread), researchers will definitely have to deal with each of these individually in order to really move the bar on human longevity, even if CR (or CR mimetics) could keep the wheels from falling off our aging bodies for (very optimistically) a decade or even two.

 

--Dean

[Zeta]

 

[Aubrey has] now become an expert, and "experts tend to underpredict".

 

Yes, Aubrey is an expert, but he's also (unhappily) a fundraiser and a politician, spending most of his time advocating for more support for research into anti-aging interventions. If anything, those are strong motivations to over-promise rather than under-predict. I consider his seemingly pessimistic timeline (from our personal perspective anyway) in the face of this strong temptation to sugar-coat the situation to garner more resources be refreshingly honest, and a sign that he's probably better calibrated than most in the anti-aging field.

 

Good points, Dean, though he also needs to emphasize complexity to draw funds away from those emphasizing simplicity....

 

 

I consider it nearly impossible to argue with Aubrey's observation that there are multiple distinct causal pathways in the aging process (seven by his count). While I'm not certain he's covered them all (see the two previous posts in this thread), researchers will definitely have to deal with each of these individually [...]

 

I remain unconvinced. With stem cells and whole organ replacement we would have everything solved aside from the brain (a huge aside, of course!).

 

Stem cell therapies are advancing rapidly, as is whole organ replacement, but, to be sure, it will be a while before we can replace most organs. An ear is one thing, a kidney, with its complicated architecture, is another.

 

But I confess I'm being overly optimistic. I have too many health problems, and see the end approaching too rapidly, not to sink into fantasy thinking a bit.

 

Zeta

[Dean Pomerleau]

Zeta,

 

This is the second time you've said something along the lines of the following:

With stem cells and whole organ replacement we would have everything solved aside from the brain (a huge aside, of course!).

Stem cells and organ replacement will certainly be a lifesaver for a people with failing organs, will likely be helpful for everyone eventually. But I'm curious about the basis for your contention that stem cell therapy and whole organ replacement will be a panacea that defeats all the causes of aging outside of the brain. These two therapies don't seem to address several of the seven causes of aging that Aubrey and other researchers have enumerated:

1. Extracellular Junk
2. Intracellular Junk
3. Extracellular Crosslinks
4. Cell Loss and Atrophy
5. Death-Resistant Cells
6. Cancerous Cells
7. Mitochondrial Mutations

Clearly #4 and perhaps #7 could be addressed by stem cells and organ replacement. But our number one killer, cardiovascular disease, seems to mostly be some combination of causes 1-3, and wouldn't be addressed. And neither stem cells nor organ replacement seem likely to fully address cancer, our second leading killer. While stem cell therapy might help by keeping immune cells in top shape and able to kill cancerous cells better, the available evidence suggests that organ replacement generally increases cancer risk.

 

--Dean

[Zeta]

 With stem cells and whole organ replacement we would have everything solved aside from the brain (a huge aside, of course!).

 

Stem cells and organ replacement will certainly be a lifesaver for a people with failing organs, will likely be helpful for everyone eventually. But I'm curious about the basis for your contention that stem cell therapy and whole organ replacement will be a panacea that defeats all the causes of aging outside of the brain. These two therapies don't seem to address several of the seven causes of aging that Aubrey and other researchers have enumerated:

1. Extracellular Junk
2. Intracellular Junk
3. Extracellular Crosslinks
4. Cell Loss and Atrophy
5. Death-Resistant Cells
6. Cancerous Cells
7. Mitochondrial Mutations

Clearly #4 and perhaps #7 could be addressed by stem cells and organ replacement. But our number one killer, cardiovascular disease, seems to mostly be some combination of causes 1-3, and wouldn't be addressed. And neither stem cells nor organ replacement seem likely to fully address cancer, our second leading killer. While stem cell therapy might help by keeping immune cells in top shape and able to kill cancerous cells better, the available evidence suggests that organ replacement generally increases cancer risk.

 

--Dean

 

Dean, pardon delay.

 

My response is simple: If one replaces organs, one replaces 1-7! If one replaces all organs, one replaces all instances of 1-7: problem solved -- except: most of us don't want to "replace" the brain....

 

Some organs can't, of course, be replaced very easily -- like the skin and vasculature. And that's where a stem-cell-based, "cell-by-cell renewal" approach would have the most promise, but I'll admit that might be a long way off. But promising work has been done in "dedifferentiating" cells, turning them into stem cells, and slowly rejuvenating tissue. That approach may not solve #3 and, esp., #1 above, of course. But #1 and #3 seem easy to solve by other means.

 

Zeta

[Zeta]

This, for ex., solves 1-7 -- within the kidney:

 

Scientists Can Now 3D Print Transplantable, Living Kidneys

 

But, as I noted, skin and ("extra-organ") vasculature (the vasculature within an organ would of course be young in every way) will be much trickier, and, again, there's the huge problem of the brain.

 

Zeta

[Zeta]

Note, a video where Aubrey seems to be very positive about replacement as a general strategy, even when it comes to the brain (though not whole brain replacement, of course):

 

https://www.youtube.com/watch?v=dt_fP3fCkNo.

 

(Skip, for ex., to 08:05.)

 

Zeta

[Zeta]

More news on a simpler (than SENS) approach:

 

Whole-body Induced Cell Turnover: The Future Of Cell Therapy?

[Dean Pomerleau]

Zeta,

 

Note there is a thread devoted to this paper on whole-body cell replacement, started by Sthira.

 

--Dean

[Dean Pomerleau]

Here is a new video with Aubrey, Liz Parrish & Bill Andrews by Adam Ford for World Future Day on Defeating Aging.

 

At around 31:00, Ford asks them how long until an effective strategy to halt or reverse aging will be available. Bill Andrews' answer is ridiculous - one year with sufficient funding. Aubrey is very tactful in the way he says Bill is crazy, and answers "15-20 years before therapies reach the clinic". I'm not sure if he means "clinical trials" or "clinical treatment available" in that timeframe. He also qualifies that estimate with the fact that it assumes sufficient funding, which he estimates to be about ~$50M/yr. He says progress is being slowed by about a factor of 3x due to insufficient funding now, and explicitly mentions 60 years as an ETA if funding does not increase.   Hopefully funding won't ramp down when Aubrey's inheritance runs out in the next year or two...

 

But he expresses optimism about a 'snowball effect', where scientific progress begets enthusiasm which begets funding which begets more scientific progress, in a virtuous cycle. So he doesn't think it will take 60 years, but it all depends on how long it is until funding ramps up, and of course, how difficult unknown challenges turn out to be. 

 

--Dean

 

 

[Guest Tom B.]

As people reading/posting here can surely appreciate, there are many disadvantages to ageing; however, there are also some occasional advantages. One advantage is that being older, one gains experience - "we've seen all this before". Now, the past is not always a predictor of the future, but statistically, it is more often right than wrong. In this spirit, let me - an oldster past 50 - share the benefits of my experience, such as they may be. I've been interested in life extension all my life, and I've eagerly devoured literature on the subject for decades now, since my early teens. I've been around many, many, many, many periods of extreme hope and optimism that this or that therapy will work for this or that - notably during the entire biotech boom of the 80's and the genome boom of the early 2000. The pattern is always the same. Like energy from fusion, cure for cancer and the like: we are always - ALWAYS - 10-20 years away from the promised land.

 

It is in this spirit that I read the amusing musings and predictions from energetic agents involved in these worthy enterprises - in this case Mr. de Grey. I don't doubt his commitment and the need to proselytise, given how hard one has to work to secure funding. However, to all his predicted numbers I'd append "and when we finally reach the time of this prediction 10-20 years later, please append another 10-20, and upon reaching that, append another 10-20- and so on ad infinitum". It will always be just over the horizon, like a mirage in the desert. And then one day you croak, and another energetic agent will find a new mirage and the show will go on. I'm sure one day we'll reach these goals, as well as achieve world peace and nirvana, but I'm afraid we'll all be long dead. As my favorite artists and friends and family continue dying of millennia-old diseases, I look back sardonically upon the War On Cancer and the continual mirages just across the horizon... although I think they've finally actually given up any predictions in favor of a grim acknowledgement that things are infinitely more complicated. And that's just cancer - a pathology. Now people are making claims for something much more fundamental and almost unprecedented in biology - conquering aging? Aah, the infinite optimism of humanity. 

 

This is not to rain on any parades. I - like any sensible person - would love for all such projects to be spectacularly successful. But old age has saddled me with this terrible thing of "having seen it all before".

[Todd Allen]

Guest_Tom_B, my completely unqualified opinion agrees with you.  In particular the idea that $50 million / year is sufficient funding to solve the 'problem' of aging in only 10 to 20 years doesn't seem to make sense when one considers that there is over $420 million in current grants funding research into cancer, http://www.cancer.org/research/currentlyfundedcancerresearch/grants-by-cancer-type

and that cancer has been a major research focus for more than 10 to 20 years and while tremendous advances have been made it is still a major killer.  If solving aging is really so easy wouldn't it make more sense to devoting a big portion of the cancer research funding to solving aging first?