In Essence, All Aging Research Revolves around the Science and Advocacy of SENS, the Strategies for Engineered Negligible Senescence

Today's popular science article for consideration is the usual mix of frustrating and interesting remarks that result when various researchers are convinced to talk to the press on the subject of SENS rejuvenation research. I in no way exaggerate when I say that all approaches to the research of aging, all of the intent in aging research, all of the fundamental disagreements in the field, ultimately revolve around SENS, the Strategies for Engineered Negligible Senescence. The advocacy and the science of SENS are the moral and technological sun in this solar system, for all that many of those orbiting it apparently would rather things were otherwise. Is the point of aging research to cure aging, rejuvenate the old, and greatly extend healthy human life spans? Is the point of aging research to move as rapidly as possible to this goal? In the SENS view, yes, and with specific plans for how the medical control of aging can be realized. Everyone else in the field must be defined by their answers to these questions, and thus by their position on SENS, their differences from the SENS view.

When looking in on this situation from the outside, it is important to realize that (a) more than fifteen years after its introduction, SENS research still represents only a tiny fraction of the research field, (b) that its origins are as an outsider group, its founders entering the research community because they were sufficiently outraged by its lack of action with regard to aging to put aside their own plans, and (c) that only SENS and SENS-like research appears to be producing the basis for cost-effective interventions to address aging as a medical condition. Given this situation, no-one in the field can really ignore SENS, but there are nonetheless a great many who would prefer to.

In one sense, the SENS approach to aging, considering it as the downstream consequence of fundamental damage that should be repaired, has already won the war of ideas: establishment research groups have taken up their own SENS-like agendas based on identifying damage and addressing it in order to turn back aspects of aging. Researchers now argue over how to effectively treat aging rather than remaining silent. Senescent cell clearance, on the SENS list for more than fifteen years on this basis of many lines of research from the past few decades, has in recent years been proven to be a reliable means of reversing numerous aspects of aging in animal studies. It is well on the way to the clinic, under development by a number of funded startup companies. This significant progress has required a fraction of the expenditure to date on, say, calorie restriction mimetic drugs or other ways to slightly slow aging that are diametrically opposed to the SENS philosophy. These are approaches that do not repair root cause damage, but rather try to alter metabolism to slow down accumulation of damage. Senescent cell clearance therapies to date demonstrate very well the point that SENS approaches are cheaper and better, as we should expect of any attempt to repair damage rather than just slow it down.

Yet in another sense, SENS has barely touched on the bigger picture of research and development. It is a tiny fraction of the ongoing work in the field. The vast majority of aging research remains investigative only, with no intention of producing therapies. Only a couple of the characteristically SENS approaches have made it into the mainstream in a big way, senescent cells and amyloid clearance. The first working, real rejuvenation therapies are not yet available in the nearest clinic. Yet tiny fraction as it is, it is the fraction that matters when it comes to results, as the past few years of work on senescent cell clearance has demonstrated. When the only thing that really matters is results, given that the successful treatment of aging is a matter of life and death for all of us, that puts SENS firmly at the center of the field.

SENS as a line of advocacy and set of specific research programs to achieve rejuvenation has helped to fundamentally change the research community since the turn of the century, from one in which no-one could talk about treating aging as a medical condition, to one in which young researchers publish openly on this topic and the first therapies are moving towards the clinic. Yet the researchers whose field has been changed remain on the whole remarkably unwilling to credit any of this to the small community of advocates and researchers who have occupied the central point of strategy and intent in their field. Even those researchers who ten years ago penned a letter dismissing all of SENS as something other than science, the presented evidence for the merits of senescence cell clearance included, find it hard today to admit outright that they were completely wrong. But everything of importance in aging research comes back down to SENS in the end: are research groups working on meaningful ways to turn back aging, or are they just wasting time and funding? What matters more than saving all of the lives lost to degenerative aging? Than preventing all of the suffering caused by degenerative aging? This is a meaningful question in a field that is still in the ragged process of a slow - and apparently sometimes reluctant - change from pure research to applied research, and whose members often seem quite hostile to the SENS advocates who ask these and other pointed questions.

Can Human Mortality Really Be Hacked?

It's just after 10:30 a.m. on a pleasant weekday morning at the SENS Research Foundation, a biotech lab in Mountain View, California. I've come to speak to its chief science officer, Aubrey de Grey. The 54-year-old's long hair, tied back in a ponytail, is turning gray, a change that would be unremarkable if he weren't one of the world's most outspoken proponents of the idea that aging can be completely eradicated. Unlike most scientists, he isn't shy about making bold speculations. He believes, for example, that the first person who will live to be 1,000 years old has most likely already been born. In 2009, de Grey founded the nonprofit SENS Research Foundation, the world's first organization dedicated to "curing" human aging, not just age-related diseases. The organization, which conducts its own research and funds studies by other scientists, occupies an unassuming space in a small industrial park. Its walls are affixed with large, colorful posters illustrating human anatomy and the inner workings of cells.

The basic vision behind SENS is that aging isn't an inevitable process by which your body just happens to wear out over time. Rather, it's the result of specific biological mechanisms that damage molecules or cells. Some elements of this idea date back to 1972, when the biogerontologist Denham Harman noted that free radicals cause chemical reactions, and that these reactions can damage the mitochondria, the powerhouses within cells. De Grey takes this concept further than most scientists are willing to go. His 1999 book argued that there could be a way to obviate mitochondrial damage, slowing the process of aging itself. Now SENS is working to prove this. Its scientists are also studying other potential aging culprits, such as the cross-links that form between proteins and cause problems like arteriosclerosis, and senescent cells that stop dividing but accumulate inside us, secreting proteins that contribute to inflammation. They're looking at damage to chromosomal DNA, and at "junk" materials that accumulate inside and outside cells (such as the plaques found in the brains of Alzheimer's patients). As de Grey's thinking goes, if we could figure out how to remove senescent cells and other damage using approaches like drugs or gene therapy, along with other types of repair, we could potentially keep our bodies vital forever.

This desire to eradicate aging has, in the last decade, inspired a mini-boom of private investment in Silicon Valley, where a handful of labs have sprung up in SENS' shadow, funded most notably by tech magnates. It's this influx of wealth that has brought novel anti-aging theories out of the scientific fringes and into gleaming Silicon Valley labs. De Grey notes that developing the means to make everyone live forever is not cheap. Further, immortality, it turns out, is not such an easy sell: Most people don't like the idea of living forever. "I find it frustrating that people are so fixated on the longevity side effects," de Grey says, clearly irritated. "And they're constantly thinking about how society would change in the context of everyone being 1,000 years old or whatever. The single thing that makes people's lives most miserable is chronic disease, staying sick and being sick. And I'm about alleviating suffering."

Judy Campisi works in Novato at the Buck Institute for Research on Aging, a gleaming profit research institution. "For 99.9 percent of our human history as a species, there was no aging," she says. Humans were very likely to die by our 30s from predation, starvation, disease, childbirth or any number of violent events. Life spans in the developed world have more than doubled over the past century or so, but this hasn't happened through any interventions against aging itself. Rather, it's a byproduct of innovations such as clean water, medication, vaccinations, surgery, dentistry, sanitation, shelter, a regular food supply and methods of defending against predators. A biochemist and professor of biogerontology, Campisi has spent her career studying aging and cancer, and the role senescent cells play in both. She has researched these cells in her lab and published widely on the possible evolutionary reasons they remain in our bodies. She posits that for most of human history, natural selection didn't favor living to old age. Evolution protected younger people so they could pass along their genes, and senescent cells play a very important role.

"One thing evolution had to select for was protection from cancer," she says. "Because we are complex organisms, we have lots of cells in our body that divide, and cell division is a very risky time for a cell because it's easy to pick up a mutation when you are replicating three billion base pairs of DNA." If a cell doesn't divide, there are fewer chances for such a mutation to creep in. "So evolution put into place these very powerful tumor suppressant mechanisms - senescent cells - but they only had to last for 40 years at the most." Senescent cells contribute to inflammation, and "inflammation is the number one risk factor for all diseases of aging, including cancer." The idea that senescent cells contribute to aging was first postulated in the 1960s. Yet 50 years later, scientists still don't entirely understand the role they play. All Campisi can say definitively is that, for most of human history, there was "no evolutionary pressure to make that system better because everybody died young."

When I ask Campisi why some scientists talk about "curing" aging, she says it comes down to getting interventions approved. "There are people who want to consider aging a disease for the purposes of going to regulatory agencies and having a specific drug able to treat a specific symptom, which you can only do if it's recognized as a disease." But Campisi stresses that living forever is not the goal of most research on aging. Instead, she says it's primarily aimed not at life span but "health span" - increasing the number of years that people can remain physically and mentally agile. Campisi has known de Grey for years, collaborates with SENS and even serves on the organization's advisory board. I ask what she makes of his assertion that someone alive today will reach the age of 1,000. "I have to tell you Aubrey has two hats," she says, smiling. "One he wears for the public when he's raising funds. The other hat is when he talks to a scientist like me, where he doesn't really believe that anyone will live to 1,000 years old. No."

In 2006, the magazine MIT Technology Review published a paper called "Life Extension Pseudoscience and the SENS Plan." The nine co-authors, all senior gerontologists, took stern issue with de Grey's position. "He's brilliant, but he had no experience in aging research," says Heidi Tissenbaum, one of the paper's signatories and a professor of molecular, cell and cancer biology at the University of Massachusetts Medical School. "We were alarmed, since he claimed to know how to prevent aging based on ideas, not on rigorous scientific experimental results."

More than a decade later, Tissenbaum now sees SENS in a more positive light. "Kudos to Aubrey," she says diplomatically. "The more people talking about aging research, the better. I give him a lot of credit for bringing attention and money to the field. When we wrote that paper, it was just him and his ideas, no research, nothing. But now they are doing a lot of basic, fundamental research, like any other lab." In marked contrast with de Grey, however, Tissenbaum doesn't see aging itself as the problem. "I don't think it's a disease," she says. "I think it's a natural process. Life and death are a part of the same coin." Meanwhile, scientists are trying to understand why the brain deteriorates over time, losing mass and neural circuitry. Tissenbaum and others are trying to understand these mechanisms, hoping to find new treatments for neurodegenerative diseases. But she doesn't expect any intervention to keep humans healthy forever. "It may be that the brain has a finite life span," she says.

Comments

Dr Aubrey de Grey, doesn't believe we live to a 1000 years and only uses it as a funding catchphrase according to Dr.Campisi? I am honestly surprised! Wow that is sad to know. Hopefully we find the technology to live to a 1000 years. That would be great! And I hope the field acts quickly to unite under the SENS banner and give them the credit they deserve, so that we can accelerate rejuvenation research further ahead at a high pace!

Posted by: Akschith at May 24th, 2017 9:36 PM

I've concentrated nearly all of my charity money on SENS, the amount of good that will be returned per dollar spent is easily much more than any other group can accomplish. I can't encourage strongly enough for everyone to do the same.

Posted by: Corbin at May 24th, 2017 9:55 PM

@Akschith: I don't believe that to be correct. So far as I know de Grey stands by his paper on the subject: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC423155/

I suspect it more likely that Campisi has her own opinions on what de Grey does or does not believe, or the actual intent of her comment here was more related to timelines and was in some way misinterpreted or mangled by the author.

Posted by: Reason at May 24th, 2017 10:08 PM

Does anyone know project 21 of the SENS foundation will reach its 2021 quota of 50 million or at have an idea as to where the funding for the project is heading!? Right now I haven't heard anything from Peter Thiel or other wealthy people about funding SENS. Clinical trials take a long time and if SENS doesn't get that amount by then, combining that with regulation in the US, a lot of us might be well into their late middle age or old age and be beyond help even if the therapies do arrive within our lifetimes as they will have minimal to negligible effect . I also haven't heard of any of the other 6 categories that need to be repaired coming into the mainstream like cellular senescence yet. People in the general populace who are accepting of the idea of radical life extension and being biologically younger won't trust, believe and help the SENS foundation if results are not shown and I guess this is partly the reason as why Project 21 has been properly funded yet. It is a vicious loop of not being adequately funded and thereby not producing the expected results. I hope this situation resolves itself soon.

Posted by: Akschith at May 24th, 2017 10:46 PM

I think Campisi has just done some serious harm to our cause. She knows damn well how little funding SENS gets and she just painted Aubrey as a huckster. Yeah.... Good move. As if we didn't have enough snake oil salesmen, false promises and failures of the past hindering our cause. Now I'm not naieve enough to think that Aubrey doesn't have caveats or reservations when talking shop to other scientists, but he IS trying to change the defining characteristic of our species. More importantly, he's trying to convince our species that it's even possible. That takes a certain amount of marketing, and given the mountain he has to move, I accept that, but when a member of your own advisory board speaks out in that way painting you as "less than genuine", it's damaging.

Shame, I always thought of Campisi as one of the good guys. We need something, ANYTHING to move the needle on the human condition. Not helping Judith, not helping at all.

Posted by: Mborbely at May 24th, 2017 10:48 PM

@Mborbely It's a frightening thing to see that the very scientists that Dr.Aubrey needs to collaborate with him are painting him in a negative fashion. This is also an article in an influential magazine like the Smithsonian! I hope this doesn't have far reaching implications for the funding of project 21 due to displeased wealthy investors or any investors in general and hobble his future endeavors in this field. I seriously hope, these scientists that work with him clean up their act! I for my part will donate to SENS but it's a measly amount and not millions of dollars which is what is required to move forward the needle on bringing rejuvenation biotechnologies to life which is very frustrating since people are dying everyday and we need to up the pace, so that we have a chance to not face the grim prospects of frailty and death!

Posted by: Akschith at May 24th, 2017 11:03 PM

I imagine it's just Aubrey being conservative with other scientists - when they're doing collaborations and research, getting an extra 900 years isn't the concern - getting the first 30 is. Aubrey's made enough comments in papers and in private that confirms he believes in the living to 1000 stuff anyway, even outside of needing to attract funding.

Posted by: Miranda at May 24th, 2017 11:32 PM

Also, the Project21 trials are, for now and to my knowledge, Ichor Therapeutics LysoSENS based therapy (marketed for macular degeneration), Unity and Oisin's senescent cell clearance (marketed for arthritis), and a few companies for amyloid clearance (likely marketed for Alzheimer's and heart disease). There's a few others - Gensight for MitoSENS and a few senescent cell companies - and it is smaller stuff, but that's generally in place. Bear in mind that I bet part of mainstream appeal is "these scientists encode an enzyme in your lysosome to clean up lipofuscin" or "these scientists create copies of mitochondrial genes and place them in the nucleus to prevent damage" isn't as flashy as "These scientists clear junk cells and expand (median) lifespan in mice!".

Posted by: Miranda at May 24th, 2017 11:49 PM

From the way things look does anyone believe or have hope that people of Aubrey's generation who are in there 50's now will live to benefit from the first rejuvenation therapies and become biologically younger? My parents are in their 50's and have worked very hard most of their lives which put a lot of physical and mental stress on them as i am sure is the case for a lot of you. As it is normal to want what's best for your family and friends I certainly want them to benefit from the first rejuvenation therapies and hope this therapies come in time for both my parents , you and me. It truly is such a scary time since we don't whether these therapies will be successful and arrive at the clinic in our lifetimes and if so when they will be available with all the funding issues that are currently present!

Posted by: Akschith at May 24th, 2017 11:57 PM

« More than a decade later, Tissenbaum now sees SENS in a more positive light. "Kudos to Aubrey," she says diplomatically. "The more people talking about aging research, the better. I give him a lot of credit for bringing attention and money to the field. When we wrote that paper, it was just him and his ideas, no research, nothing. But now they are doing a lot of basic, fundamental research, like any other lab." »

It's interesting how Heidi Tissenbaum still refuses to acknowledge the validity of the SENS approach. Instead she sidetracks about SENS being good as a research effort - regardless of its merits.

Posted by: Spede at May 25th, 2017 12:40 AM

I'm not surprised at all by Campisi, she was very skeptical on the SENS conference last year as well.
And the article is the same old, same old, researchers always say in these types of articles. It does make me mad, but at the same time there is very little I can do about it.

Posted by: Anonymoose at May 25th, 2017 1:45 AM

As much as I support SENS, I must say that in the long run it is not the ultimate goal. The ultimate goal would be to modify the human body in such a way that it can maintain itself so that no relevant damage occurs or it is cleared by the body itself. That's not impossible and evolution has already done it in some organisms, but it's damn complicated. I can only speculate when that knowledge will be available but it will surely be much later than SENS therapies.

Posted by: K. at May 25th, 2017 3:57 AM

In all interviews with de Grey, he (or the interviewer) somehow stresses that the main goal is to alleviate the suffering and disease of old age, and radical life extension is just a side effect.
I think it would be useful to not be apologetic, and stress that this is a heck of a side effect!
I understand that this appeals to most of the public (in some strange way), but perhaps pointing out that much longer lives are at the least much more productive lives could be useful for ultimately advancing our goal.

Posted by: anps83 at May 25th, 2017 4:48 AM

@anps83 It's kinda hard to make a big deal out of it when you're constantly bombarded with the "overpopulation"/"inequity" arguments.

Posted by: Anonymoose at May 25th, 2017 4:52 AM

@Reason You think we can push Aubrey to do a round table with Campisi so they can have a heart to heart talk on the topic? Ever since that quip on the conference last year I've been personally hoping to hear them debate eye to eye.

I've read the Campisi/Vijg paper from years ago and I don't see anything in it that would give her that much conviction in any hard limit to the human lifespan. I'd really like to hear them go at it - if there is a hole to the SENS proposal I'd very much love to hear about it so we can start thinking of ways to solve it.

Posted by: Anonymoose at May 25th, 2017 5:01 AM

Every article about aging ultimately ends up sounding the same. It talks a little bit about Aubrey and his/SENS' background and goals, then goes into repeating the same circle of objections and people who disagree that are mentioned in every other article. I know that more people are supposedly supporting this field, but it sure does not feel like it. It just feels like nothing is ever painted in a positive light. And when it is, it's a half hearted attempt. Just my .02.

Posted by: Ham at May 25th, 2017 5:06 AM

I also really wonder how much the researchers who promote health span really buy into that concept. Is it a PR move, as to not offend anyone by suggesting we live longer than what's "natural"?

Posted by: Ham at May 25th, 2017 5:26 AM

@Ham Support for the field is definitely on the rise.
Support for SENS on the other hand ... it's kinda static.

Posted by: Anonymoose at May 25th, 2017 5:30 AM

It's hard to tell with such negativity always surrounding the field. I agree with the SENS point.

Posted by: Ham at May 25th, 2017 6:18 AM

Regarding Aubreys statement of the 1000 year lifespan:

The problem with this kind of prediction is that no has ever lived that long til now - so Aubrey cannot know what challenges (biological, that is)encounter you, although you can make certain predictions I think. For example, it would not be enough to break glucosepane as at some point the other crosslinks will accumulate in a relevant amount. Another example, even if mutations in the nuclear DNA are not a reason for aging during our present lifetime, this might might change when you live a couple of centuries. Also, if you live long enough, other proteins than amyloid and tau might aggregate in an amount that is damaging to the cells/body. I think there is some uncertainty associated with this.

Posted by: K. at May 25th, 2017 6:36 AM

The usual format of healthspan apologists who either believe that is a worthy goal or are saying it to protect their career from those who believe it is a worthy goal. I would pay their lip service no mind, we all know what the goal is: health, independence, prevention or cures for diseases and with a bit of luck a longer life to enjoy all that. I believe in time once results begin to arrive such healthspanners will increasingly become the minority.

We are working hard at Lifespan.io to convince the wider public and are speaking today in Madrid at the International Longevity and Cryopreservation summit in Spain. We believe that convincing the public is the key to kickstarting the avalanche and popularizing the subject. If an individual researcher does not believe anything beyond healthspan is a worthy goal then we do not have to raise funds for them. Quite simply donating to SENS and supporting projects for repair approaches on Lifespan.io lets us decide what we want. Don't let conservative researchers decide for us we have the power.

Posted by: Steve Hill at May 25th, 2017 6:40 AM

"if mutations in the nuclear DNA are not a reason for aging during our present lifetime, this might might change when you live a couple of centuries."

Exactly one of my criticisms of SENS and why I am behind Hallmarks of Aging personally. Thankfully people like Sinclair and others are working on DNA repair because even if SENS is right and DNA damage isnt significant to aging in our lifespan now it almost certainly will be later.

However my previous point stands. By fundraising and supporting the projects and researchers who share our ambition we get a say in how science moves foward.

Posted by: Steve Hill at May 25th, 2017 6:43 AM

@Steve Hill or @SENS supporters: MitoSENS addresses that problem and are superior in that way it takes the mitochondrial DNA into the nucleus.

Posted by: Norse at May 25th, 2017 6:48 AM

@Norse I am talking about nuclear DNA not mtDNA this is not the same problem though DNA and mtDNA damage are both part of the Hallmark: Genomic instability and both need fixing. Sinclair is dealing with nuclear DNA damage and also we just found out that mtNDA also relies on NAD to fix itself too. I am well aware of what MitoSENS is about and fully support that approach.

Posted by: Steve Hill at May 25th, 2017 6:53 AM

@Steve Hill Easier said than done. There's not a whole lot of people ready to collaborate with SENS and as it happens Campisi is one of the few. So how do we cut her off?!

Reality of the matter is, most people in the mainstream especially the old dogs like Campisi - she's been working in the field for what? Almost 45 years now? - aren't at all concerned with lifespan. And all of the young scientists are working under one of the older ones like Campisi.

I'm not sure we have a choice as you put it.

Posted by: Anonymoose at May 25th, 2017 6:54 AM

@Anonymoose you dont have to cut her off at all. She is doing the work of SENS regardless of if she believes the healthspan line.

But we absolutely do have a choice and we can and are launching projects led by scientists who support SENS and its goals. CellAge is an example of this, young scientists who are independent of the system, funded by the community and now making progress.

So yes we do have a choice and that is exactly what Lifespan.io and LEAF are about and what we are doing. We have scientists lined up with projects to launch currently and not a single one of them talks about healthspan. So you tell me, do we have to accept the status quo? I think not.

Posted by: Steve Hill at May 25th, 2017 6:59 AM

Just to be clear:

When someone is talking about health span but at the same time doesnt want to think about life extension, then they're not talking about health span really. Life extension inevitably follows from health span otherwise its pseudo-healtspan as these 2 are closely connected. There's no death without disease or molecular damage.

Posted by: K. at May 25th, 2017 7:11 AM

There is a comment posted by a person calling himself Hytler. That I think is also a problem the field strives with. Perception from outside. What if dictators lived for 1000 years. I myself have received comments like that when promoting these causes. "So, you want to start where Hitler left''? My answer is:"It is a tragedy how many peoples lives that person (Hitler) affects still som many decades after his death." (By hampering life saving research). But the person was not intellectual enough to understand mye response. That person still takes lives.

Posted by: Norse at May 25th, 2017 7:12 AM

@norse and for every idiot or objector there are dozens open to the idea if it is presented in the right way and the message is right. We will be publishing an article about message delivery and format soon and in fact this is the theme of our speech in Madrid tonight. We are also interviewing Aubrey apparently soon as it has been agreed at the Hotel today.

But short of telling you we have a choice I am not sure what more I can add to the situation. We have people who will listen and people who will not. In my experience it is better to ignore those who wont listen and move to those who will. Why waste time arguing with 1 person when I can reach 10-20 others who will listen?

Posted by: Steve Hill at May 25th, 2017 7:20 AM

Steve, I thank you very much for your insightful comments. I support both Aubrey's SENS project and David Sinclair. As for Dr.Judith, I don't know how to feel about her since she has great influence and commands a great crowd and I don't want to lose all that attention by not supporting her. But she is always putting down Aubrey's work in the press. You claim that Judith is actually doing SENS work but what if she is one of those pseudo-health spanners as she promotes herself in the press!? Also Buck doesn't really need support from people like us right since they are so well funded? The second point i wanted to make is we desperately need to grow our community and Campisi's slander against Aubrey doesn't help our cause in any way by turning people away from him since she holds so much influence. I know Reason, you and everyone here including me will support Aubrey but as Anonymoose said the support for Aubrey and Rejuvenation biotechnologies is static right now and these researchers who talk this way are not helping us! As I understand right now senolytics that combat cellular senescence is the only therapeutic field I believe the mainstream public is aware of and the field is catching steam. As for the other 6 categories, they are still not at the same stage as the cellular senescence field and mainstream public is not aware of them. To bring them to that stage, Aubrey needs a lot of funds and these researchers are making things very difficult for him which worries me the most since we can't wait 15 years for each field to catch momentum. Maybe you can tell me if Aubrey is actually gaining support since you fundraise for SENS causes but I can't see his support increasing with all the negative publicity. Finally, the biggest problem is as someone said it before the young researchers that are always following Judith campisi and not the SENS education program. I am thinking not many young researchers are following Aubrey because it is better for them to follow Judith for their career. This is scary since Aubrey doesn't have close enough to a team of young researchers and senior researchers as other institutes like Buck. Couple this researcher shortage with the funding for the other 6 categories other than cellular senescence and you have a worrying trend. As for the projects you talk about like Cellage, there are not many of them and i always check lifepspan.io's current projects page. There are a few other projects mostly from sens that are already funded but i don't a lot of current projects there based on the other 6 categories waiting there from SENS or people who follow its vision. I am not to be offensive but just saying what i see there. These are all concerns i have as a support

Posted by: Akschith at May 25th, 2017 8:11 AM

@Norse exactly that yes.

Posted by: Steve Hill at May 25th, 2017 10:48 AM

Wow, so much hand wringing because a researcher following the SENS approach of damage repair doesn't at present believe that 1,000 year lifespans are possible.

William Bains has also said that he doesn't believe repairing the seven classes of SENS damage will end aging. But there doesn't seem to be much concern about this.

All the handwringers/naysayers forget that you don't have to convince the entire population, just enough to get some more funding then let the results speak for themselves. "There is nothing so powerful as an idea whose time has come".

Posted by: Jim at May 25th, 2017 12:06 PM

Hi, 2 cents,

I think it's because it does not address all damages (and the therapy must be started before 50 years old or its too late/catchup mopup game) and as such claiming a 1000 year lifespan; is like saying I know how to make a rocket in my backyard - thus, the moon is next. Building a spaceship/shuttle is a major endeavor and takes time; and money (BillionS, not millions) and people, and people willing and a whole lot of other things. The same with life extension. Rejuvenation is on its way but its at the very start - that is why I believe (anyone can flame me, just a 2 cent nothing more, these not facts), that a 1000 year lifespan is possible but not with the technology available now or in the near future (the enxt 100 years). I think it's why scientist keep a reservation and don't make outlandish claims of someone living a Millenium long - barely no animal does, can you name one single animal that does (except hydras)... too them it's the real of fantasy no matter how much 'damage reduction hypothetizing' done. SENS addresses some of these damages, not all of them and there are still other types of problems (replicative end problem, lamina/histone loss, cell cycle arrest, redox loss, mTOR among others, and so on and on and on); it's the biggest maze humans have ever faced and finding a way out is going to be hard; very hard. With that said, it is still worth trying, lives could be saved and improved. Mrs. Campisi is not being a downer; but rather I think a realist that is not trying to put it down but to be real in terms of expections (nothing is certain that's sure but a 1000 year lifespan is a dream of everyone (almost) but it 'sounds' to people like a Fantasy made-up.
I think it's also why AdG keeps it 'low radar/low profile' on his LEV paper, he aims at 'improving health' rather than a 1000 year lifespan as a goal (a 'fortunate' side effect'...); and that's because the 90% of medical research thinks he's baloney with that claim - it could be possible - but in Reality - it is Ultra-Slim : Jeanne Calment reached 122, she one of the few (or sole ?) who reach 122...0,0000000000000000000000000000000000000000001% chance.
And now you understand why you may people are Unbelievers - WHo Want to believe :
Make an immortal mouse. Voila. (it sounds 'very easy to say'...just like saying 'make someone live a 1000 years'. On paper it sounds nice, in real it sounds unreal/ultra-exaggeration).

AdG aim for 500 years or less, that's (more reasonable/real) feasible - animals Reach That. We're next (I hope :).

Posted by: CANanonymity at May 25th, 2017 4:05 PM

How incredibly rude. I normally don't comment on this blog but some of the comments on this post need some addressing.

Honestly, I don't understand why there is all this unnecessary hostility and berating of Judith. I can pretty much guarantee that nothing Campisi said is going to have any detrimental effect on the SENS platform or Aubrey's work. So what if some of the scientists Aubrey collaborates with are skeptical about 1000 year old lifespans or focus on "healthspan"?

I don't understand why that is a problem when these very same researchers and scientists are working on the bits of the puzzle that will ultimately bring the SENS platform to fruition and into the clinic.

I think focusing on healthspan is a perfectly reasonable approach. The side effect of increasing healthspan will be an increase in lifespan anyways. Even if ALL researchers working in the relevant fields used "healthspan" in their terminology, and ALL researchers flatly said that longevity is NOT a focus of their work (which even Aubrey has been saying in recent years), the end result will still be robust human rejuvenation that will inevitably lead to longer lifespans and possibly longevity escape velocity.

I think some of you immortalists need to get a grip. You are not millionaires or billionaires and you don't have a lot of influence, yet the impression I'm getting is that you think you know better than anyone else on how to raise the necessary funding and awareness for this field. But it is clear that that isn't the case.

Here's a newsflash. The vast majority of people do not care about longevity or living a long time. It's nice that some of you want to live a 1000 years or more (as do I), but you have got to realize that most human beings are relatively short term planners, and are largely thinking about their next 5-20 years tops. The vast majority of people are far more concerned about not getting sick, decrepit, disabled, losing their youthful appearance as they get older as well as the loss of physical and mental function over the next few decades of their life. They want those things fixed, rather than hearing endless dribble about "longevity" and thousand year lifespans.

Again, I repeat, healthspan and lifespan are pretty much inextricably linked. No choice of terminology one way or another is going to change this. If you keep people healthy, the side effect will be greater lifespan.

However, you are far more likely to get money in the door if you focus on health (which pretty much all of humanity universally looks at in a positive light) rather than "lifespan", "longevity", or "immortality".

I mean it is unreal reading some of these comments. On the one hand, some of you are getting upset at the use of perfectly reasonable terms like healthspan... in campisi's words meaning ... "increasing the number of years that people can remain physically and mentally agile" (phrases that can ACTUALLY get real money in from real every day people and wealthy individuals) instead of "living forever"..... and IN THE VERY SAME BREATH, you complain that when you raise issues like "immortality", people tend to have knee jerk reactions about overpopulation and dictators. Have you ever thought that maybe this indicates that Campisi's choice of words are better than what you prefer?

At the end of the day. The ONLY thing that matters is getting the funding for the relevant research related to the SENS platform and getting the initial 30 years of robust healthy life. Whether people really believe in the more distant projections and feasibility of SENS over the long haul is frankly irrelevant. Let SENS damage repair approach first demonstrate that it is indeed the optimal approach to dealing with age related diseases and disabilities (which I suspect it is), and get those first 30 years of life.

I suspect it is precisely the 1000 year lifespan, the obsession with longevity (as opposed to health and quality of life), of "immortality", and "living forever" and what have you that has done the most amount of damage to people's perception of SENS, and contributed immensely to the shortage of funding moreso than anything any skeptical researcher has said or any terminology (no matter how incorrect) any scientist has used.

The best approach is to just get aging recognized as a disease/treatable condition and talk about health/vibrancy and to demonstrate why the SENS approach is superior (as opposed to most approaches that address either symptoms of age-related or attempt to tinker with metabolism).

Even if some people are under the mistaken impression that healthspan can be increased without increasing lifespan, SO WHAT? SO WHAT? As long as they are working on, funding, or advocating the correct projects and using the correct approach to target age related conditions, the end result will be the same.

We do not need broad public support for a "war on aging". All we need is for a sufficient recognition, acceptance, and funding of the damage repair approach and "rejuvenation biotechnology" to become a well established cornerstone of regenerative medicine.

If you can convince people and wealthy individuals that breaking crosslinks, stem cell therapies, developing senolytics, clearing amyloids, importing mitochondria, etc etc can be useful for curing X,Y,Z diseases (as well as getting aging itsself recognized as a disease or treatable condition by the regulatory bodies) and/or keeping people healthier and more vibrant overall, then that's frankly all you need. The side effect of quite profound longevity will simply sneak up on us, and by that time, whatever kneejerk backlash some people have about "overpopulation" or whatnot will be irrelevant.

Every single one of the SENS strands (as well as perhaps nuclear mutations over the long haul), can, in some way shape or form, if brought to fruition, have profound effects on improving our health (whether it be addressing a specific age-related diseases or improving functional health over all). You don't even need to mention longevity at all. In fact, depending on who the audience is, it might be better to avoid talking about lifespan, and sidestep all the common tired old objections to it.

I very much welcome the fact that Aubrey has focused his more recent appearances far more on differentiating the damage repair/rejuvenation biotech approach and explaining why it offers the best option for our long term health (as contrast to lifestyle/diet, fixing metabolism, or bashing symptoms with geriatric medicine) rather than focusing on "longevity".

People almost universally appreciate health and quality of life. The same is not true for "longevity". Health and quality will confer quantity. There's no reason to beat ourselves up trying to convince people that extreme longevity is either desirable or achievable. The entire SENS platform and all similar research can be presented and sold to venture capitalists, philanthropists, investors and everyday folks without ever having to focus extensively on lifespan.

So again, cut Judith Campisi some slack. She has probably accomplished and contributed significantly more to "move the needle" in this field than the majority of the commenters on this page.

Posted by: Peter at May 25th, 2017 4:16 PM

"We do not need broad public support for a "war on aging". All we need is for a sufficient recognition, acceptance, and funding of the damage repair approach and "rejuvenation biotechnology" to become a well established cornerstone of regenerative medicine."

I dont agree at all with your view that we dont need public support. We indeed do and this is what LEAF is focused on as well as supporting fundraising via Lifespan.io. The rejuvenation biotech movement need popular support ultimately to gain more funds. Each year that amount has risen for SENS which shows support is growing. A big community attracts popular support and celebrity interest as well as funds to do the heavy lifting that in turn attracts investors. This is currently a bottle neck and we have discussed this in detail here:

http://www.leafscience.org/bottlenecks-in-research/

"Every single one of the SENS strands (as well as perhaps nuclear mutations over the long haul), can, in some way shape or form, if brought to fruition, have profound effects on improving our health (whether it be addressing a specific age-related diseases or improving functional health over all). You don't even need to mention longevity at all. In fact, depending on who the audience is, it might be better to avoid talking about lifespan, and sidestep all the common tired old objections to it."

Correct and we are already focused on optimizing messaging. We pitch from 1: Health, 2: Independence 3: Disease prevention/cures. Selling longevity/immortality is a fools game, the public dont respond well to this message and the work by Pew and Patridge show this and explain exactly why. The answers to why the public dont engage are available to read, if only more people in the community would do the groundwork.

We have addressed a conference in Madrid today with this very message, that the community needs to change the message and how it engages if it wants to succeed. In fact SENS is one of the most successful if not the most successful orgs in this field for that reason. They dont sell longevity and they are very wise to avoid highlighting it as anything more than a side effect.

As I said before, Judy is working on SENS things so it doenst matter as long as the work gets done. My previous comment stand that Lifespan.io gives us the choice of what projects to support anyway and as long as we are moving in the right direction its all good.

Posted by: Steve Hill at May 25th, 2017 5:04 PM

@Peter

Hi Peter ! 2 cents... Very great measured and thoughtful points ! THank you !

'The side effect of quite profound longevity will simply sneak up on us, and by that time, whatever kneejerk backlash some people have about "overpopulation" or whatnot will be irrelevant.'

AdG spoke of this longevity side effect (I'll admit myself I focus more one the bing numbers (like living to 150 (very tempting ;) I might be a closet fauximmortalist not a fatalist with a pinch a realist, but I try to not, because that is overtly optimistic (1000 year life) and it's true it is damaging to the 'health' goal as it creates distortion and exaggeration which undermine the Credibility of rejuvenation and thus of funding going to it (as you said)).

With that said we cannot escape it's a freight train, humans could finally maybe live forever know knows, human endeavor knows know boundaries - the subject was going to come up because it touches ethical issues (death, overcrowing, resources, blablabla), I agree with you - to not Focus too much on Longevity and - in the immediacy - to improve health to save lives.

'The side effect of quite profound longevity will simply sneak up on us, and by that time, whatever kneejerk backlash some people have about "overpopulation" or whatnot will be irrelevant.'

Just a 2 cent, this side effect may not happen. Sens and many forward therapies may not touch all of these damages and problems - as such, aging and health are not necessarily intricately entwined. You need health, but health can be sepereated from Longevity. That is a fact :
seen in C.elegans.

As such, we could live (morbidity compression) to 120 a full healthy life - and we wil die at a 120 as is planned - While taking therapies such as SENS. I don't want that niether you I think (sorry my typos). To say, if you take the therapies - all damage - Clear - All Check - Perfect Health = Side Effect of 1000 year. Facts show that health and longevity are co-dependent and co-inter-independent. It would pant out like that and we would get 'the fortunate side effect' of longevity or immortilaty. It's what I call a 'f...if you do and f...if you don't mechanism'. The body is made with a Limit and it was carefully evolved that way (And so many other animals). It is a extremely intricate balance and wethere you put some more black or some more white in that Yin Yan sign; doesn't make any difference - it'S a balance and this balance - dies. Anyways, I'm just raving on, you have a good sensible take. THanks.

Posted by: CANanonymity at May 25th, 2017 5:09 PM

"Jeanne Calment reached 122, she one of the few (or sole ?) who reach 122...0,0000000000000000000000000000000000000000001% chance."
No, it's one in 7.3 billion. Learn some freaking arithmetic.

Posted by: gwood at May 25th, 2017 5:12 PM

PS : 'It would - not - pan out like that and we would - not - get 'the fortunate side effect' of longevity or immortilaty that is thought of going to happen if health is kept perfect (health improvemnt alone won't make you live a 1000 years that is a near total assured outcome). It's because there is confusion in the terminology of Aging and Health - confoudend yet are they seperatable and classified as two things (even if they are dependent and reaching other - you see how complicated/mixing it is).

Posted by: CANanonymity at May 25th, 2017 5:15 PM

@gwood

Hi gwood ! It was mostly a demonstrative example of the minimalistic chances; you're right though it's 1 to planet pop, thanks !

Posted by: CANanonymity at May 25th, 2017 5:20 PM

"I think it's why scientist keep a reservation and don't make outlandish claims of someone living a Millenium long - barely no animal does, can you name one single animal that does (except hydras)"

Mostly basal metazoans:

Scolymastra joubini (15 000 years lifespan)
Monorhaphis chuni (11 000 years lifespan)

potentially immortal through transdifferentiation:

Laodicea undulata
Aurelia sp.1
Turritopsis dohrnii

Posted by: K. at May 25th, 2017 5:38 PM

Hi K.,

Thanks for that, I did specifiy (except hydras (metazoans, jellyfish among others) :)
I should have been more precise, and said 'can you name on single Mammal animal that does'

Posted by: CANanonymity at May 25th, 2017 5:45 PM

PS: I remember, I wrote a comment here almost like eons ago (2 years?) that there was a scientist, forgot his name, whom said the reason they have immorrtality is because they are 'simple' (cellularly and organ speaking) while we are 'complex' animals with lots of complexity and capacity (walk, talk, think, etc...they don't have that). Simplicity = Ease of Maintenance of Host = Immortality. Complexity = Difficulty of Maintenance of Host = Evolution 'Balancing' playing = Mortality. The Cost for that : Mortality.

Posted by: CANanonymity at May 25th, 2017 5:51 PM

@CANanonymity

There is clearly no mammal species with this lifespan - but not because evolution coulnd't produce a 1000 year lifespan in a mammal but it would have no chance of being selected for in a world of fast changing environments. The evolution of long lifespan of basal metazoans to short mammalian lifespan is driven by massive gene loss including loss of DNA repair genes and the establishment of the Weissmann barrier. Interestingly, expressing some proteins that were lost long ago in the evolution of the lineage leading to humans can rejuvenate cells or help them cope with stress that mammalian cells now are not equipped to do. The loss occured because evolution is blind and longevity was never a goal to reach - there are no goals in evolution. The evolution of postmitotic cells like neurons conferred clearly a selection advantage that however stripped these cells of mitotic waste segregation. The capability of movement is what seperates many short-lived higher animals from long-lived lower animals and plants. Movement likely increased the mitochondrial mutation rate which then led to the segregation of germline and soma - note the low mutation rate of mitochondria in plants as opposed to animals. The aging process is deeply routed in the evolutoniary history of our species because of the short lifespans of many of our ancestors which didnt allow for selection against pleiotropy of protein function.

Posted by: K. at May 25th, 2017 6:29 PM

PPS : I found my old comment, it's Dr. Uri Frank :

''
Quote of Dr. Uri Frank on jellyfish immortallity :

" So why don't humans keep their pluripotent cells as adults [humans, just like in the immortal Irish jellyfish/sea anemone Hydractinia] ? It's a good question. Keeping them in a complex body like ours is probably too dangerous, as they can easily form cancer. It's not [so much] a problem in simple animals - [these jellyfish's pluripotent cells] they would probably cut a cancer off.
The price to become complex is to lose the ability to be immortal. "

Quote by Jennifer Viegas :

" Eternal life, from an evolutionary standpoint, however has a big drawback. Due to asexual reproduction, the species as a whole retains very low genetic variation. This means they could be particularly vulnerable to climate change [not have the adapted genes] and not enjoy immortality after all. "

Evolutionarily, it would make sense ressource-wise, low creational-ressource demanding simplistic pseudo-animals get the immortality. Simplistic systems are easier to maintain error free/damage free/mutations free. Complex ressource demanding animals, such as human who get to do lots of stuff with their complex bodies - get the mortality. Complex systems are harder to maintain error free/damage free/mutations free. Things even out.

1. http://www.ncbi.nlm.nih.gov/pubmed/19000774
2. http://www.ncbi.nlm.nih.gov/pubmed/9849895?dopt=AbstractPlus
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306686
4. http://www.biolbull.org/content/218/2/113.short
5. https://www.jstage.jst.go.jp/article/galaxea/14/1/14_53/_article
6. http://www.irishtimes.com/news/science/immortal-irish-marine-animal-provides-hope-for-research-into-ageing-1.1500113
''

Posted by: CANanonymity at May 25th, 2017 6:29 PM

Great points you bring,

'There is clearly no mammal species with this lifespan - but not because evolution coulnd't produce a 1000 year lifespan in a mammal but it would have no chance of being selected for in a world of fast changing environments.'

You are right with neurons being selected with special abilities of junk clearing.
I guess we are doomed (?, kidding), we live fast changing environments today and we constantly move - it's like not 'working' like those simple 'immortal plants and trees' that don't move and have the 'old genetic make up' that we lost and make us mortal. We should get 'selected', I think we are sort of doing that because evolution used to change us to its liking; now it's the inverse, we change evolution in the lab to our liking. But it still doesn't change the fact we are in those environments that were detrimental to previous immortality in those low forms (metazoan).

Greenland sharks are the longest live 'complex' animal of the planet (500 years), ok it'S not a mammal but another fish, a mammal, the Bowhead whale live 211 years MLSP - this means that it is quite possible for a mammal to reach 500; if one did reach over 200 - it's just double in the shark (double slower aging ? but clearly, they share similar mechanisms :
extremely protracted maturity (become sexually capable-the whole IGF-mTOR-replicative/spontaneous cellular senescence/cell cycle arrest thing again), slow metabolism (whale's heart drop to like 20-30 beats a min), same for Greenland ones...they can go in freezing water (that dramatically slows metabolism and developmental growth) 0 and thus, over 2 to 5 centuries to get to the size of a 18-wheeler - becayse they are soooo slow to reach sexual adulthood (puberty) and once they do, their metabolism is nill (dead?)..same thing for Quahogs who live 500 years - too. These real examples that unlock possibity of living over 150. Our metabolism and bodies are totally different but they show us it's possible.

Posted by: CANanonymity at May 25th, 2017 6:54 PM

@Steve Hill

"I dont agree at all with your view that we dont need public support. We indeed do and this is what LEAF is focused on as well as supporting fundraising via Lifespan.io. The rejuvenation biotech movement need popular support ultimately to gain more funds. Each year that amount has risen for SENS which shows support is growing. A big community attracts popular support and celebrity interest as well as funds to do the heavy lifting that in turn attracts investors. This is currently a bottle neck and we have discussed this in detail here:"

I think you misunderstood what I said/meant. I am not saying that biotechnology based on SENS principles doesn't need broad public support. I completely agree that increased public support could in turn bring greater attention to the field from wealthier individuals. What I am trying to say is that it doesn't necessarily need broad public support for the specific goal of "increasing lifespan". You do not have to convince people that aging is bad and ought to be eliminated so that we can increase our lifespans. You can do that with life extensionists, but with everyone else, you might be more successful in framing it differently. For people not interested in longevity to begin with, it may be more useful to simply present SENS as developing a novel way of doing medicine for the elderly and what kind of health outcomes we may see, and most importantly, how the approach is different from and better than most other medical research taking place.

Focusing on increasing lifespan may convince some people that are already somewhat interested in longevity, but that is not going to get you support from the broader public sufficiently fast. For a lot of people, health, youth, physical/mental functions are a much better sell than hearing how much longer they'll live. In order to gain broad public support, you have to be able to also appeal to people who have no interest in longevity whatsoever (but that do have an interest in medicine and health), and simply convince them that SENS is the most promising approach for medicines of the future that would radically enhance people's health and wellbeing.

And then you can proceed to give numerous examples of how each of the SENS strands (and individual projects within each strand) would be useful in treating X disease (Alzheimers, atherosclerosis, osteoperosis) or Y age related condition (sarcopenia, loss of skin elasticity, fatigue, immunosenescence). You could also point out, for instance that a particular disease or condition is caused by particular type of aging damage (or combination of damages) that accumulate throughout life, and that the best hope we have of curing that particular condition is by removing or repairing the mentioned damage.

Sure, you can present all this research under the banner of "life extension", but my point is that it doesn't have to be like that with all audiences. You can just as legitimately present it as a novel and groundbreaking way of doing medicine (while making sure to explicitly distinguish how the approach is better than others), but without necessarily having to dwell on extending life.

So, to sum it up, I do not think "life extension", "longevity", "lifespan", "immortality" or any of those concepts or terms need any sort of broad public support. Rejuvenation biotechnology, like what SENS, lifespan.io and various startups and university labs who are pursuing the damage repair approach is what needs more public support. Not necessarily the idea or goal of extending human lifespans.

This is why I am saying, that just because some researchers, scientists, philanthropists, or just every day people are not interested in longevity, or do not believe in the feasibility of radical life extension doesn't mean that they should automatically be dismissed from being potentially significant contributors to the progress that will inevitably bring about these things.

This is why I don't understand what some people's problem is with Judith being a little more conservative and stating that the primary goal is "increasing the number of years that people can remain physically and mentally agile" as opposed to living forever.

By the way, I am aware of LEAF and support the work they and lifespan.io do. Even on that link you provided is a paragraph that basically summarizes what I am saying:

"There are a number of sociological studies (see the list of suggested reading below) that show just how important it is to properly explain the connection between aging and age-related diseases, and the causal relationship between aging prevention, health improvement and longevity - longevity being a side-effect of better health. "

^

This right there is the issue. So many people in the longevity/life extension community enthusiastically talk about indefinite lifespans and preoccupy themselves with addressing "concerns" of skeptics. But, don't spend nearly the time and effort explaining how age and age related disease are basically inextricably linked. What the public (and therefore the potential future funders/philanthropists) need to hear more of is the fact that aging CAUSES these diseases, and if they wish for these diseases/conditions to be cured/eliminated, then the best way to do that is to periodically repair the underlying cause ( some aspect(s) of the aging process(es) ).

It is much better to sell the idea that curing certain diseases will require aspects of aging to be fixed rather than saying that aging and death sucks, but we might be able to live to 1000, and then having to address a bunch of objections.

People need to understand once and for all the direct causal connection between aging and the various diseases of old age. My point is that this does not require necessarily broad acceptance of the feasibility or desirability of extreme life extension.

Posted by: Peter at May 25th, 2017 7:14 PM

I don't think we are doomed because we can do something about it. Let me just tell you that I'm trying to indulge in the real complexity of the aging process, starting with an evolutionary reconstruction that is huge. The things I'm learning from that reconstruction already is that SENS is not wrong - the damage that occurs in our cells and body just arises because our cells never had the selection pressure to deal with them - if they would have had it our genetic makeup and thus also protein makeup would be different or at least there would be site variation in the proteins. But there is not one solution to the problem as long as you can effectively repair the damage. In other words you don't have to do it the "evolution way" which is always slow and complex. In the end things are a bit more complicated though but nevertheless there is no need to be overly pessimistic.

Posted by: K. at May 25th, 2017 7:28 PM

"For people not interested in longevity to begin with, it may be more useful to simply present SENS as developing a novel way of doing medicine for the elderly and what kind of health outcomes we may see, and most importantly, how the approach is different from and better than most other medical research taking place."

But that's exactly how SENS has been advertising itself for years.
I won't bother reading the rest of your wall of text if you can't even be bothered to open sens.org.

Posted by: Anonymoose at May 25th, 2017 7:35 PM

If you can't "be bothered" to read someone's post perhaps don't comment on it.

Posted by: Barbara T. at May 25th, 2017 8:26 PM

I attended today to the International Cryonics and Longevity Summit (and will attend today) and almost all the longevity related talks, apart from the talk of Aubrey, were about research related to the Hallmarks, which Aubrey himself said is some form or some version of SENS. There were not much "messing with metabolism" talks (only a few talks about epigenetics and big data) and there was a lot of tissue engineering and tissue cryopreservation talks. I will start a blog when I return home.

Posted by: Antonio at May 26th, 2017 12:04 AM

Typo, "I attended yesterday."

Posted by: Antonio at May 26th, 2017 12:06 AM

@ Peter :

The problem isn't one of terminology, it's one of ideology. Healthspanners are often the ones who berate the lifespanners, they are the ones who make lifespanners pass for lunatics, because the public opinion is largely owned by healthspanners, they are the doxa.
Healthspanners are the ones who deny that longevity is the byproduct of health, whilst Aubrey's thesis is that to get longevity you need health in the first place.
Bad faith or blindness, you can see how detrimental the attitude of healthspanners can be.

Regarding Campisi herself, I don't have much to say, except that her allegation that Aubrey is playing a « double game » is borderline.

Posted by: Spede at May 26th, 2017 12:31 AM

Peter, how would you go about convincing a significant part of the public that SENS is a better approach for eliminating disease? Most people want cures but don't care about the details.

Posted by: Florin Clapa at May 26th, 2017 12:39 AM

PPPS: 2 c feel, I think there is a confusion at large (I sort of included myself in that but I try to remove myself because studies make doubt my own previous thoughts, it's like it changes one day to the next, up and down. IT makes me think of when they said smoking is bad and then..smoking is good for you...I'm lost...and then back again to 'smoking is bad'...who do you believe anymore), in that helath and aging are 1:1, it's not the case in certain studies. HEalth is needed to continue - Average Lifespan. You need that,it's understood but to confound health = aging or health = cure of death 'because alive', it's error. it's not 1:1. There are linked together but are also (inter) independent; kind of like two friendly neighbors (aging and health): they talk to each other every other day but they don't live in the same apartment and they each have their respective apartment - but live in same building 'block house' (body). Does that stop them from communicating, no they still talk to each other but when the talking is done, they go back in their respective aparts and live their life - in Their apart, not the neighbor's. Health studies in certain animals showed that - Less Healthy ones - could Outlive the Healthier ones; and that's because Aging affects Different epigenetic and mTOR regulated mecanisms than average health in an average lifespan. Health is almost like a '2nd state', it is 'movable' and moves if you get ill; this can accelerate the process of Aging (just read Blagonosklonny's papers they are clear and true), But there is INherite Aging mecanism/program whatever ahve you that is Below that and is the Intrinsic Aging - that continues its course - wether healthy or less healthy. Below a certain 'health' threshold, aging is dramatically accelerated. The damages incurred are just byproduct of metabolism, in accelerated againg, disease happen quicker...but why do healthy people die at 100 then ? Why are they not immortal if always healthy ? Because Aging is different than Health; it's an underlying 'program/damage process' and continues its course. Ok an example (Sorry my types it's really late I'm sleepy):

Lipofuscin levels barely changed in some cases, yet the animal experienced disease or illness (Lipofuscin is a manifestation of intrinsic aging and can be decoupled from health state; same thing with certain AGEs or junk; they can make unhealthy but have little weight in your intrinsic Aging process). Showing they are co-inter-independent and dependent at the same time (Who knew that was possible), they are coupled and Uncoupled. It happens so many times in studies that genetic mechanisms (and like epigenetics and gene pleiotropy) just 'act' upon certain conditions or instances; it's almost like a self-deciding thing (because it 'auto-regulates/auto-compensates' itself with feedback mechanisms) that it would or would not do something).

So to recap 2 things : 1-Aging (underlying, it has an end and you die). 2-Healthy(second. it is movable and can wildly change, as long as you get back to health it'S ok you'll live your 'Average' lifespan and you will die at 120 or below because of NUmber 1-.).

Just my 2 cents feel of it (I really use to think being always healthy meant eternal life, I was wrong I was confounding them 'into 1 thing and the same' when they are two things).

Posted by: CANanonymity at May 26th, 2017 1:59 AM

@CANanonymity
Health - as described by the mainstream and described from the damage repair perspective is different. A 100 old man currently can't be healthy.
Worms - from where the whole health=/-lifespan idea came from - bad model animal to study health. We don't know what health is for worms. What we measure is how much they move around. That's not in any way a valid measure of health ... or anything really.

Posted by: Anonymoose at May 26th, 2017 5:28 AM

@Peter

"This right there is the issue. So many people in the longevity/life extension community enthusiastically talk about indefinite lifespans and preoccupy themselves with addressing "concerns" of skeptics. But, don't spend nearly the time and effort explaining how age and age related disease are basically inextricably linked. What the public (and therefore the potential future funders/philanthropists) need to hear more of is the fact that aging CAUSES these diseases, and if they wish for these diseases/conditions to be cured/eliminated, then the best way to do that is to periodically repair the underlying cause ( some aspect(s) of the aging process(es) )."

Yes that is the problem right there. Too much daydreaming and focusing on living forever and other such things instead of delivering effective messages in the right format. We will be publishing a deep article shortly about this problem based on our speech in Madrid yesterday at the Cyronics and biotechnology conference in Spain.

I believe we do see eye to eye regarding the public afterall. Good to know and we will keep moving foward with perfecting the message.

Posted by: Steve Hill at May 26th, 2017 5:50 AM

Posting in a largely pointless 58-comment slapfight thread.

Absolutely everything that Peter said is true. Nail on the head.

Who cares whether anyone believes that damage repair can result in indefinite lifespans rather than longer, healthier ones? Damage repair doesn't need belief to work, damage repair needs researchers and funding.

Posted by: Slicer at May 26th, 2017 9:41 AM

PPPPPS:

That's True.

Though it needs demonstrable proof - to increase 'belief' - and make the big payers come. You have to 'sell' it to them - but since we don'T have any proof buy heresay and a mountain of studies (paper 'thin air'...and no 'rejuvenated mouse' yet..) people are still skeptic and stay that way. But, in the End, it doesn't really matter; what

matters is getting the message through even if we need to bulls...a bit and spread thick; who cares, people 'will buy it'; just say ok 'we focus on health and your diseases will be gone'...it's a true message - in the immediacy - to get the Credibility and the Funds; we can't (still) curing aging but we can cure health problems (enough) - people care just about that (those that wish to live no more than 90 years old). They represent the Large mass of people who's MAin Concern is staying healthy and disease-free. And as Peter said don'T care of living over a 150 years old or of life extension wording (I feel sad for them, but people make their own decisions and if they feel 100-120 is 'Good Enough' 'Had Enough' 'Long Enough' 'Now Boring' to pull the plug; it's their decision).

The Rest of Us (TROS) the 'illuminati' (kidding) we wish to live longer and of course we hope healthier - but we represnt crumbs...we are not the majority. Thus the onus lies on the major amount of people who are not sold (and never will be they don't care - They Want to Die) on life extension but on 'health improvement'.

Health message = Money (by reach of the mass who fear diseases and don't give a s..about long life extension = advancement of 'Rejuvenation' SENS...later on, we get back to 'aging' and life extension. 2c.

Posted by: CANanonymity at May 26th, 2017 11:46 AM

First, while I'm surprised and disappointed (as I have been several times in the past) by Dr. Campisi's comments here, I want to assure everyone that she is absolutely on the right side of the battle, whether as a scientist, as a close ally of Dr. de Grey and the Foundation, or as a long-time advocate of intervention in aging. She has done a very great deal to advance the cause of rejuvenation biotechnology throughout a long and storied scientific career, culminating in the development of what is likely to be the first-to-clinic senolytic therapy for human use. Whatever skepticism she may have about the limits of rejuvenation biotechnologies, everyone hoping for a future free of degenerative aging (or even for a modestly less miserable course of it) owes her a debt of respect and gratitude, and should bear that in mind when expressing any frustrations about some of her views and the frankness with which she expresses them. Consider her as one who insists on grape juice at our common celebration of Communion.

Second: life expectancies somewhat over a thousand years are exactly what would result from bringing aging under complete biomedical control while holding the risks of non-aging causes of death constant (making it actually a somewhat artificially pessimistic prediction of a future reality with such control). I am quite confident that her assessment of Dr. de Grey's assessment of the feasibility of such an achievement is in error. I am going to quite openly speculate that she arrived at her assessment of Dr. de Grey's "secret" assessment along the following lines of reasoning:

A priori, a thousand-year life expectancy is simply outlandish. No reasonable, intelligent, and informed scientist could possibly believe such a thing.
•In all of my extensive interactions with Aubrey, he has consistently demonstrated himself to be a reasonable, intelligent, and informed scientist.
Therefore, Aubrey cannot possibly believe that a thousand-year life expectancies are feasible.

Third:

Posted by: K. at May 25th, 2017 6:36 AM: Aubrey cannot know what challenges (biological, that is)encounter you, although you can make certain predictions I think. For example, it would not be enough to break glucosepane as at some point the other crosslinks will accumulate in a relevant amount. Another example, even if mutations in the nuclear DNA are not a reason for aging during our present lifetime, this might might change when you live a couple of centuries. Also, if you live long enough, other proteins than amyloid and tau might aggregate in an amount that is damaging to the cells/body. I think there is some uncertainty associated with this.

All of what you elaborate here is already baked into the cake of "actuarial escape velocity" (formally modeled here). Remember, we don't have to repair or replace all of the cellular and molecular damage of aging at once in order to ultimately achieve indefinite lifespans: indeed, we have in a trivial sense well over a thousand years to do so after having initially developed the first, decisive, comprehensive panel of rejuvenation biotechnologies. Such a panel "only" has to effectively remove, repair, replace, or render harmless a sufficiently wide range of forms of cellular and molecular damage, and do so effectively and safely enough, to grant 20-30 years of additional life expectancy to a person in late middle age.

With the quarter century of increased life expectancy enjoyed by those first beneficiaries, scientists will have time to develop further refinements and additions to the panel, expanding its efficacy, safety, and comprehensiveness sufficiently well to increase life expectancies by a further 30%, which in turn would give the recipients of such technologies even more time alive in absolute terms — and, again, win more time for medical science to deliver yet more and better rejuvenation biotechnologies, even as science's ability to develop such technologies continues to improve over time. And so on, until we had aging under complete medical control, and life expectancy would be bounded only by causes unrelated to aging (violence, accidents, natural disasters, catastrophic infections, etc).

This is based explicitly on the premise that future technologies will both improve the safety and effectiveness of our ability to remove or repair already-targeted forms of aging damage, and that we will also progressively target additional forms of aging damage that have little or no biomedical relevance today because they accumulate so slowly as to not rise to the "threshold of pathology" within a currently-normal lifespan, but that will emerge as life-threatening as other aspects of aging are brought under medical control and we live long enough for them to accumulate to such levels.

So we fully expect that we will identify AGE crosslinks in future that are either currently unknown, or that are known but that aren't of biomedical interest today because they don't accumulate to a sufficient degree as to impair tissue function. But with each new round of rejuvenation biotechnology innovation, we will be gaining progressively more time to develop means to cleave such crosslinks, even as our ability to develop such tools accelerates with the improvement of our technology and our model systems. (This is an example of actuarial escape velocity specifically discussed in the relevant chapter of Ending Aging).

Similarly, Dr. de Grey fully agrees that at some point in the future, nuclear mutations and epimutations will accumulate to a sufficient degree as to become life-threatening for reasons that cannot be remediated with technolgies that will be components of the first comprehensive panel of rejuvenation biotechnologies (viz, Whole-body Interdiction of Lengthening of Telomeres to eliminate cancer; senescent cell ablation; and cell therapy). At that point, we will need to develop additional classes of rejuvenation biotechnology to repair or obviate them.

Because it's not clear today what those technologies would be (strong nanotechnology?), you're right that we can't say with absolute certainty that this will be a resolvable problem - but it seems implausible to think that this or any problem of damaged physical structures would forever remain beyond the reach of future technologies.

Posted by: Michael at May 26th, 2017 12:06 PM

PPPPPPS:

It's almost as if Reason. you almost needed to change the Message Title of your website to
'Fightdisease.org'. (than Fightaging.org, because it muddies the message on pole who don't care of aging - but of health only, which they represent the 90% mass)just saying. 2c

Posted by: CANanonymity at May 26th, 2017 12:22 PM

@Michael

Thank your for your elaborate answer on the topic. I agree with you if actuarial escape velocity will work as you predict, but doesn't it always assume that we will have the technology to clear new forms of damage/malfunction ready always in the timeframe before this new damage kills us? You might be right that our technologies and models get better but still bear in mind that we, as the first humans ever to live that long, will be under pressure to clear that new damage before it kills us and there's no one you can ask when that will be the case because we are patient number 1. This might be pessimistic or not, I simply don't know. What if a new form of damage arises that cannot be repaired with a technology that will be ready by then to clear other damage, how long do we need to design the new technology? Is this unrealistic pessimism, I simply don't know but in my opinion we should think about future forms of damage as soon as possible although i know that we actually have enough to do with the current damage repair.

Posted by: K. at May 26th, 2017 2:29 PM

"I am going to quite openly speculate that she arrived at her assessment of Dr. de Grey's "secret" assessment along the following lines of reasoning:"

Michael, I'm going to throw up the cynicism flag and suggest that what she believes and what Dr. de Grey believe both have surprisingly little to do with what she wasn't dumb enough to tell a reporter.

I'm still fairly sure that the only realistic near-term way to solve nuclear/epigenetic damage is ship-of-Theseus gradual death and replacement. Kill some aged cells, replace with genetically perfect cells, repeat. Yes, this includes the brain. Of course, the first person to make stem cells work properly in the cerebral cortex is, after a successful self-experiment, going to become much better at getting stem cells to work in the cortex, right along with a whole lot of other things...

Posted by: Slicer at May 26th, 2017 3:44 PM
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