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A New—and Reversible—Cause of Aging (harvard.edu)
232 points by DiabloD3 on Mar 29, 2014 | hide | past | web | favorite | 87 comments



“The aging process we discovered is like a married couple—when they are young, they communicate well, but over time, living in close quarters for many years, communication breaks down,” said Harvard Medical School Professor of Genetics David Sinclair"

- Totally off topic though but I think he's describing a couple heading to divorce. Nearly all successful marriages move in the exact opposite direction.


Without intervention, the human body usually headed for divorce, in this analogy, anyway.



I think it was a case of bad paraphrasing. Another source doesn't make Sinclair sound as odd: "Much like a married couple talks to each other when they're newly married but then they stop communicating after about 20 years, at least in some cases." http://www.abc.net.au/news/2013-12-20/scientists-develop-ant...


Yep, this struck me as an odd analogy!


I think, it's not really that communication breaks down, it is more that you don't need to communicate at all because you know the other person so well by now. Then divorce happens because you don't like what you know or you realize your spouse isn't what you wanted, or the marriage becomes stronger because you anticipate your partners needs/actions without having to communicate. So yeah, the analogy is not really right.


While it is true that you learn your spouse that well, it will be long before that when you realize if don't like them.

However when you don't communicate, your lives get out of sync. At some point this has gone on long enough, the changes we go through (called life) cause people to become strangers again.

It's like two inertial systems. They drift, differently, over time and this difference accumulates. Communication between the two inertial units can synchronize them. Or a trusted third party (GPS) can give them both a course correction.


So I was supposed to be my parents GPS.


Link to the abstract on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/24582957

Original is behind a paywall.

---

I'd take all this with a grain of salt, though. The biology of aging is incredibly complex. Seemingly certain answers to the question of what causes or mediates aging (e.g. free radicals) have turned out to be less conclusive and all-explaining than researchers originally thought.


There are seven distinct mechanisms for cellular and intracellular damage resulting from aging. Improving the regulation of mitochondria could completely fix one and slow down the rate of accumulation of a few other types of damage, but that's it.

http://en.wikipedia.org/wiki/Strategies_for_Engineered_Negli...


Please note that Aubrey de Grey's theories are highly controversial and while some of these mechanisms are indeed big topics in the field, many biogerontologists have been publicly skeptical of his claims. In fact, some of these are even mentioned in your link.

The way you worded it, it seems you're implying SENS is a widely accepted theory, while in fact it's anything but (although I'd say it certainly is interesting and worthy of investigation).


If by "highly controversial" you mean "supported by many leading names in the research community" then sure. See this, and note the presence of George Church, Judith Campisi, Maria Blasco, etc:

http://sens.org/about/leadership/research-advisory-board

The SENS Research Foundation has a yearly budget about a tenth of that of one of the largest aging research labs, the Buck Institute. The Foundation funds work in a range of laboratories around in the US and Europe, and has collaborations with Oxford, Wake Forest, and so forth.

Insofar as controversy exists, you might look on it as a facet of the present dispute over modern theories of aging: camps for aging as accumulated damage versus aging as evolved programming. The accumulated damage side is much bigger but split into several factions, one of which is centered around SENS.


SENS is controversial, but the cited 7 damage mechanisms are not. The way you worded it, it seems you're implying the 7 mechanisms are not widely accepted, while in fact, they are. (I only used the citation for the list of the 7 damage mechanisms. I can't easily find other lists that are as concise. I too am skeptical of his proposed fixes.)


Its a promising result, but a lot of mice experiments don't have the same effects on people. It would be ironic if this technique failed on humans subjected to a lot of exposure to botox :-) The fear is that suddenly not only would the rich get richer, but they would never die. That leads to some fairly depressing scenarios.


Don't bother with those immortality consequences scenarios until you see a real general working treatment for cancer (something way more than "it cures 80% of the cancers in 80% of the cases"). If you live long enough, you will get cancer - basic molecular biology and probability and thermodynamics will take care of this. Also, the side effects of most regenerative treatments are increases in the risk of cancer.

Also, don't bother with "the super-rich becoming super-genetically-enhanced" scenarios - all known genetic therapy technologies have as side effects increasing the risk of cancer.

Basically, cancer is the mythical dragon guarding the tree of eternal-life and super-gene-therapy, so while it's still alive, being super rich and having access to all regenerative medicine and anti-aging therapies will make a difference, but not such a big one, so don't worry :)

(And yeah, finding a "general" solution to the cancer problem is truly hard, maybe even impossible for the absolutely general case - ie, you'll still have rare forms of cancer that don't respond to any know therapies, and as you live longer and longer the probability of bumping into one such form will approach certainty. And getting a better and better treatment for each type of cancer doesn't seem to go much faster until we get a specific set of breakthroughs in nanotechnology that could be applied to this specific problem.)


> If you live long enough, you will get cancer

Is this true, though?

The really old rarely die from cancer, it seems. http://z3.invisionfree.com/The_110_Club/index.php?showtopic=...


Because the heart and circulatory system accumulate damage and fail first in very old age. Yes, the risk of cancer fall a little with old age (or at least the speed of progression - most of the very old that die of heart disease and stroke probably have lots of incipient cancers that would have taken much longer to kill them). This risk never falls to zero or negligible and all anti-aging and regenerative therapies will reverse this - in a system where everything works slower and worse, even cancer works slower.

And if you look at that list for example, you see that most of those causes of death are thing that would have been harmless to a person without cardiovascular diseases. Taking some of the examples: the long list of pneumonias is because old people that get stuck in bed because of a stroke or heart failure usually get "aspiration pneumonia" or that the buildup of fluid in lungs due to hart failure leads to a series of complications fatal when coupled with a pneumonia. The only causes from that list that were probably not related to cardiovascular disease, besides the cancers, are probably the 2 kidney failures (...if you don't assume things like renal artery stenosis due to aterosclerosys or aterosclerosys and hypertension related kidney disease). Also, things like "organ failure" are a way of describing the consequences not the cause - there was a cause for that organ failure, just that the pathologist didn't bother looking into it. And unless there is a real suspicion of criminal action, no path exams for the causes of death in old people are really conducted scientifically anywhere in the world.


It's not that the risk of cancer goes down it's that all the other risks goes up. Remember really old people have a 50/50 chance of death per year risk and your cancer risk is lower than that. But long term even a 1 in 200 risk of death per year will still kill you.

Anyway, I don't really see the problem with rich people living longer lives. Dynastic wealth still lingers around and ends up in the hands of incompetent people which is probably a worse outcome.


This is a book about the tradeoffs (if you're God/Darwin) of death. Really, really interesting book :

http://www.amazon.com/Sex-Origins-Death-William-Clark/dp/019...

He first frames the problem. Firstly pointing out that not all parts of the human body are subject to death. Every cell in your body was alive 180000 years ago when the human race first emerged, and even 3 billion years ago when the first cells really started happening. Every cell in your body and, indeed, you yourself are part of the original cell's lifespan.

Second he goes over a lot of experiments that indeed point out the trade-off that God is making here : either you die, or you become a cancerous blob, over time. Not creating the situation where cancer will eventually win is also a no-go, for other reasons.

Thirdly, he points out, mathematically, what death is and isn't for a human. It isn't nearly as clear-cut as you might think. He also gives the philosophical reasons why death may indeed not be the end of existence (well it isn't, if you have kids, for obvious reasons, but it may also not be the end of your conscious existence for other reasons).

Really, this book will change your thinking on death a lot, and after reading it you will understand that not dieing is something that will come with massive consequences.


Your falling pray to survivors bias. If you pick a cell and after each time it reproduces you pick just one of it's decedents as the 'original' then they don't actually last all that long on average. Sure, single celled organisms don't have a built in lifespan but without reproduction anything can wipe them out and you can easily find an average lifespan that's not all that long.

As to redefining things so there is only a single cell on the planet that's meaningless. Transcription errors occur all the time to the point where most of the cells in your body don't share the same DNA. Some people even contain a large number of their siblings cells to the point where DNA tests are less reliable than you might think. http://en.wikipedia.org/wiki/Chimera_(genetics)

Multi celled organisms are best thought of like a country it's an agreement between a group of similar cells. As such theirs plenty of edge cases where something is both a viable single celled organism and part of an a collective. Specialization is more efficient but not really necessary. As such it's easy to see just how multi celled organisms evolve, but also how cancer is basically inevitable because breaking that agreement does not prevent a cell from being viable in the short term. It also demonstrates that sharing DNA is not really nessiary as for example gut bacteria play a vary useful role dispite sharing any DNA with their host.

PS: In the life sciences edge cases can get really strange. As in the closest genetic species to humans is a bunch of single celled organisms not monkey's. http://en.wikipedia.org/wiki/HeLa


> Not creating the situation where cancer will eventually win is also a no-go, for other reasons.

What are these reasons?


They don't die _from_ cancer, but they tend to _have_ cancer when they die.

Tumours in old people grow slowly.


> Tumours in old people grow slowly.

Anyone else read this and fantasize about the world's most ironic cancer treatment? If we could somehow speed up the aging process... (No I'm not serious...)


More like tumors in old people who did not die from the cancer are tumors which grew slowly.


I'm pretty sure if possible, serious anti-aging technogy will drop in price due to incredible market demand. It's highly unlikely the compound relies on resources that are extremely rare.

Even if that were the case, someone would quickly find a way to replicate the procedure without the rare resources.

Likely the things in the way would be governments and corporations trying to profit through IP.

In that case, black market tech would be developed and you could likely go to an unregulated / 3rd world country to get the procedure done.


Just to be clear, increasing demand implies shifting the demand curve rightward, and increases the price.

The dynamics of economies of scale that we are familiar with are related to chance that suppliers can lower their marginal costs if demand also justifies a fixed cost in suitable technology. And furthermore, if there is a big enough market and enough suppliers, the market price will approach the marginal cost of production.

Imagine someone wants you to make a spoon that they'll buy from you. It takes you an hour to whittle one out of a piece of wood, and you charge $100. Then they want ten more using the exact same method you used on the first one. Ten hours whittling sounds like even more of a hardship than an hour, so you charge even more per spoon. A thousands spoons painstakingly whittled? Nope.

Now imagine on the other hand, they want you to make them a plastic spoon. Making one plastic spoon is going to be a lot more difficult than whittling one wooden spoon. And yet, if they want enough of them, and you can use any technology, your costs might start to approach $0.01 per spoon.

Anyway, since we think of anything that's to become a viable business in terms of how it can scale, it's easy to reverse the outcomes of changes in supply or demand in the base case where no technology or methods are changing.


I didn't say mere "increased" demand, I said "incredible" demand. I meant to imply that economies of scale would develop, as I imagine most will pay everything they have for the ability to live forever. (At least I would, as long as I was purely rational. I can imagine getting bored of life in 500 years or so, but I doubt it).


The political consequences will be interesting. One of the consolations if living under a tyrant is that they will, eventually die. I wonder if having Robert Mugabe around for another 40 years would excite Zimbabweans. The flip-side is that citizens could get more politically active if they couldn't rely on death to prevent gerontocracies.


Another interesting flipside might be that people become less willing to participate in a revolution for the sake of improving a few decades of their own lives and the lives of future generations when the risk of dying in a revolution means potentially giving up hundreds of years of one's own useful living.


North Korea's tyrants eventually die, but that doesn't help as long as they have equally tyrannical descendants ready to take over.


In 2005 Charles C. Mann wrote "The Coming Death Shortage" (http://www.theatlantic.com/magazine/archive/2005/05/the-comi...), which attempts to imagine what a world with drastically lengthened lifespans might look like.


We'll have effectively created a new breed of super-mice though.


Step 1. Get rich. Same as it ever was.


> but they would never die

Challenge Accepted. God. /s

On a serious note, this could be charming, but still, most people die, not because they were too old., in fact a very few people hit their biological age limit which i guess is 100 ~ 130. They are still many challenges such as diseases, road accidents which are the No. 1 cause for death.


The rich would not get richer. They would stay alive and stick around until they got poorer and eventually died.


In Larry Niven's Known Space books, some of the rich stuck around so long that they became hyper bored and so decided to become super criminals. He has one such minor character who is a woman over two centuries old, with all of the experience and knowledge that entails, with the body of an 18 year old.


Asked a buddy who ain't that smart on what he would do, if he could live 300 years.

He said: "I'd rob a bank, big time."

I asked why he would do that and he said that he could give the money to a trustee and sit his time and become rich afterwards.

So your story sounds legit to me. And I just asked for 300 years. Living 16.000 years like in the movie: "The man from Earth", was way out of his graspable zone. And he started arguing about god would kill you and so on...


When you rob a bank and get caught, they don't let you keep the money.


Tell your buddy to take a decade out of his life and become a NASCAR driver. Then take another decade to become a top-flight Bluegrass banjo player. I think those trump whatever life experience he'd get from robbing a bank.


aren't they already basically super criminals?


That's not how capitalism works. Your earning potential increases with your capital, eventually making talent and effort negligible factors.


The first generation makes the fortune, the second generation spends it, the third starts over.


What happens if that second generation never replaces the first?


"A witty saying proves nothing."


You really haven't understood how this works


Here's a link to the newscientist article on the same discovery: http://www.newscientist.com/article/dn24784-turning-back-tim...

And the actual paper (the full paper is behind a paywall): http://www.cell.com/cell/abstract/S0092-8674(13)01521-3



Thank-you for that. Reading now. So far it looks like good science.


Working link to actual article: http://www.cell.com/retrieve/pii/S0092867413015213


Here's a better article that describes the same work: http://hms.harvard.edu/news/genetics/new-reversible-cause-ag...

Less hype, more technical detail.


Anti-aging divide? I'm all for anti-aging, I was obsessed by it since my teens and got a degree in molecular biology thinking I want to dedicate my life to it, I even own dontage.com.

However, I'm concerned about implications of potentially high-price anti-aging treatments. Till now, death has been the great equalizer. Life is inherently unfair. If you are born in poverty there is high chances you'll stay there, but at least you always count on everyone dying at the end.

With high-price anti-aging treatments people who have wealth can live longer (maybe one day indefinitely) and accumulate more wealth and those without money will just dye twice or three times as fast with no way out of the cycle. You can argue historically we always had this type of divides, for example in early stages of invention of antibiotics or vaccines or ability to buy them in black market in areas where they were scarce. However, we're moving from preventing premature deaths to extending life beyond its natural extension and that brings a whole new set of issues.

Will there be enough retirement funds? If we do democratize anti-aging treatments, lets say increasing the average life span to 100 or 120. Will there be enough funding? As is, the social security is feeling the pressures of increased average life-span. So if we are able to make a 60 year olds be 20 (in some aspects of aging) or 90 year old to 30 and as the article alluded to, decrease the risk of cancers (perhaps). Then, who will pay to cover the retirement funding gap?

We're heading toward a world were you can choose to live longer and have the wealth to support your life for extended time, and those who will only live 1/2 or 1/3 as much just because they were born in a different household.

Among all the technological breakthroughs, anti-aging will probably have the biggest social impact and as a society we're not even thinking about it or are even preparing for it yet. But then again, if you have the money, why should you care.


There are many downsides to curing aging, but none of them are as bad as the current situation: 100,000 deaths every day. It's worse than you can imagine; those 100,000 people experienced decades of mental and physical decline before they died.

I think you are confused about the economics of the situation. Who will pay for retirement benefits? Aging is why we retire. If we never got old, we could work as long as we wanted.

Even if anti-aging treatments remain expensive for decades after they're invented, it will still be economically worthwhile to treat everyone. This is because age-related diseases are more expensive. Alzheimer's. Cancer. Heart disease. Dementia. COPD. These diseases slowly kill their victims, causing immense suffering. Treatments for most of them are ineffectual and cost millions for each patient. When it comes to cost, rejuvenation therapies have a low bar to get over.

My grandmother died this month. She had a form of rheumatoid arthritis that slowly turned her lungs into scar tissue. My only consolation is that her mind didn't go before she died. If only rich people could avoid her fate, I wouldn't mind a bit. The fewer people who suffer as she did, the better.


>I think you are confused about the economics of the situation. Who will pay for retirement benefits? Aging is why we retire. If we never got old, we could work as long as we wanted.

Completely backwards. "We're old and can't work anymore" is the excuse used to publicly justify finally being allowed not to work anymore in a Calvinist-capitalist culture. What we actually want is to minimize the portion of our lifespan spent working for mere wages.

Mind, one reason I've come to support anti-aging and automation advancements is davka that they force our culture to actually confront these issues, that they "heighten the contradictions" as we Marxists say, rather than pretending everything's fine and letting the system get away with its sins.


Were scientists from the past worried about this when they worked to improve medicines and public health that has increased the global average lifespan from 31 years to 70 years in the past century?

No one knows the answers to your questions, but I think there will be solutions to those problems. Birth rates are averaging out and hopefully starting to go down. Automation of work is going up. The reach of education has increased.

Also even if everyone was immune to death by aging, some actuaries showed that humans will still be limited to 400 years due to accidental death.

I think that people in different parts of the world today have life spans that are 1/2 to 1/3rd of other countries. Maybe if we're not losing all our most experienced and knowledgeable people to senility, old age, and death, we may come up with solutions more quickly.


You're missing the point. Sure suffer in the minutiae of all the implications / implementation. End of story its a single question: Do we want to have this "problem" ? Yes.

To phrase differently: Lets NOT have planes because they might burst into flames once in a while. Do you see the absurdity ?

Want to know a good way to pull yourself out of squalor? Fix aging.


Everyone says this when the subject comes up and it's ridiculous. Many countries have government subsidized healthcare. Additionally patents only last for 20 years or so. And there is no reason to think it would inherently cost a lot. Do only rich people have iphones?

And anyways, who cares? Better that some people live longer than none do.


You're assumption that people want to retire is wrong. People are retiring because the aren't capable of full work hours. With right medicine people would work more, maybe in the future there won't be such thing as "retirement funds".


I'm talking about right now. Most people are retired by 65. Now we suddenly extend their lives to 100. You think anyone would hire them again after being out of work force for 10-15 years?


One thing I'd really like to understand re: ageing is why a newborn is essentially 'reset' from an ageing perspective. I appreciate that egg cells aren't constantly dividing during a mothers life but they are still a product of division and contain DNA that can suffer from time based mutations. So if aging is due to mistakes accumulated during either divisions or time then why are children born young? I don't think this is as simple as non-viable embryos are miscarried, there must be something different in the formation of embryos that means they don't carry the aging of their parents...and what clue does that give to cure aging?


The organism is a vessel to propagate the genes. Germ cells such as embryos usually have additional defenses and repair mechanisms, such as for DNA damage, that the somatic cells lack. Since the soma are merely there to help the replication of the germ line, they receive less investment.

No creature we know of has successfully evolved the capability to permanently stave off aging. Besides the inevitable issues with fighting entropy in a complex system, how would an ageless organism compete in the shifting landscape of an ecosystem as other creatures evolve around it? How would a non-aging organism adapt? It seems likely that continually creating new generations is the best strategy for genetic replication.

Now we are at the amusing point that genes may have unwittingly experienced their own skynet event. Modern science has given us the ability to not only gaze upon our creators, but manipulate them to do the bidding of ideas.


Thanks - germ cells was the key term I was missing, this section on the germline on Wikipedia answers my original question:

Germline cells are immortal, in the sense that they have reproduced indefinitely since the beginning of life. This is largely due to the activity of the enzyme known as telomerase. This enzyme extends the telomeres of the chromosome, preventing chromosome fusions and other negative effects of shortened telomeres. Most somatic cells, by comparison, can only divide around 30-50 times according to the Hayflick limit. Certain somatic cells, known as stem cells, also express telomerase and are potentially immortal.


So then why can't we just inject ourselves with that enzyme and be immortal?


>Now we are at the amusing point that genes may have unwittingly experienced their own skynet event. Modern science has given us the ability to not only gaze upon our creators, but manipulate them to do the bidding of ideas.

Come on, man. Laugh maniacally! You know you want to.

Here, I'll start: MUWWWWWAUAUAHAHAAHAHAHAAAAA AAAAAAAAAAAAAAAHAHAHAHAHAAAAAAAAAA!!!!!!!!!!!!!!


Correct me if I'm wrong, I'm not a geneticist, but the logical reason for this sounds as simple as enriching the baby's DNA with that from the mother and father. Also only cells, which are our main building blocks, suffer from death. The death as we know it, is only affecting "bodily" species incl. single-celled life forms. DNA doesn't die, ever (given good conditions). That's why scientists can still extract DNA from animals which have been died thousands or millions of years ago.


For those working in Genetics, how much is the field upbeat about regenerative medicine in general, and Google's Calico [0] venture in particular?

[0] https://plus.google.com/+LarryPage/posts/Lh8SKC6sED1


Many of the problems surrounding funding of meaningful efforts to treat aging, eliminate age-related disease, and extend healthy life come about because the people with the biggest megaphones are also doing the least useful work.

This is true outside the scientific community, in the "anti-aging" marketplace that tries to convince people they should take supplements rather than support research.

This is true inside the scientific community, where the Sinclair labs and their work on sirtuins - which is about as useless as supplements based on the last ten years of work - get far more attention than anything that is actually likely to produce meaningful results.

This article is an example of high-road hype and nonsense. More than a decade of work on sirtuins have failed to reliably produce even a tiny fraction of the gains to health and life provided by calorie restriction or exercise. This is just one tiny slice of the broader mainstream scientific approach of attempting to alter the operation of metabolism in order to provide benefits. This is vastly complex, and will take a very, very long time to get anywhere. When scientists speak of not seeing any real progress towards human longevity in the near future, this is the approach they are talking about: take this thing, the interaction space of metabolism with aging, which is vast, and about which nowhere near enough is understood, and then try to make a better version of it.

Sure, it's possible in the long term. But we'll all be old before anyone even makes a good first pass through this enormous complexity.

Yet there is a much better path forward towards treatment of aging. This is to identify the differences between old and young tissues, something that has already been done and agreed upon by the scientific community, more or less settled for the past 20 years, and then fix them all. You don't need to delve into the interaction space to understand why or how or process or progress. You just fix it. It is the difference between repainting a wall versus understanding the deep molecular interactions of wall, paint, and weather so that you can build a better lasting paint. One of those choices is evidently much more efficient than the other.

When it's a wall, who cares? Let the paint scientists get on with it. But in the case of aging, tens of millions of lives are lost every year that passes while the mainstream screws around with metabolism to slow aging rather than building the means to repair the identified causes of aging.

Even better, while the metabolic engineers have no clear plan to produce a good end state, just a bunch of plans that have not yet panned out as expected despite great expense, the "just fix it" approach to aging has clear paths to the development of repair therapies for each identified difference between young and old tissues. So they are only limited in progress by funding.

Why does this situation exist? I blame regulation. If your work doesn't result in something that looks like a drug, sounds like a drug, and walks like a drug it isn't going to be approved. Further, treating aging is not a result recognized by the FDA - so whatever you do has to be sidelined to treat some disease of aging. In other words only applied after it's too late to prevent things from going awry. So we see marginal unambitious work on marginal unambitious treatments, the continuing random walk through the natural world's pharmacology in search of chemicals that can be crudely administered to do slightly more good than harm, because that's the only way to have even a slight chance of getting to market. Highly regulated systems perpetuate their current state at all expense, and treat change as a threat.

The treatments for aging that might actually do some good in the future are radically different from today's pharmacology. These are the repair strategies: mitochondrial gene therapy, adapted bacterial enzymes let loose in the body, targeted destruction of stem cells and immune cells run wild, that sort of thing. You can find them described if you look up SENS, the strategies for engineered negligible senescence, but there are other similar lists put forward by different research groups. The repair approach is the disruptive newcomer to the field, barely ten years old, but gathering support. We should hope that it soon wins over the mainstream, and relegates the era of paying billions for sirtuin research and other dead-ends to the dustbin of history.


Spoken like a pragmatist and not a scientist. Your argument is the equivalent of arguing no one should bother with low level programming knowledge or understanding how functions work in Ruby/Python/etc.

You're also talking like someone who has no experience with life sciences research at all and is an armchair expert. As someone who has dedicated a significant portion of my life and time to research in medical sciences it's not as easy as "fix them all." How do you 'fix' changes in protein expression without causing unintended side effects? It's hard enough to get something to work in cell culture let alone in a complex organism where compensatory mechanisms kick in whenever you do anything. We can't even get mild pain relief to work without side effects and you're talking about complex tissue engineering.

SENS is controversial at best (and utter bullshit in the eyes of many), I wouldn't go around touting it as the future of anti-aging research. Additionally caloric restriction has recently been shown to not work in humans and the early gains reported haven't translated well at all. Exercise is really the only potentially viable strategy you have mentioned.

While academia, especially at top tier institutions and mega-labs, is flawed, I would caution you to avoid jumping to conclusions because the pace of research is not to your liking. This isn't, as you so eloquently put it, painting a wall, it's a very complicated (and new) field that we still know very little about and are discovering new pitfalls every day.

Edit: Grammar


Working to do something about aging in advance of full understanding of aging is absolutely the pragmatic approach. It is engineering. It is the building of fine bridges by Romans and Victorians in advance of material science and computer simulation.

To pick one example from the SENS portfolio - by which I mean the list of techniques developed in the scientific community for other reasons and adopted as useful by the SENS proponents - allotopic expression of mitochondrial genes is absolutely a way to fix protein expression issues. It is the delivery of proteins to rescue mitochondrial function. It has been demonstrated to work in mice with no side effects for a gene associated with LHON by two separate research groups now, neither of which were affiliated with the SENS Research Foundation when they started out.

This is serious science. You might not like it or be familiar with it, but you're missing out.

SENS is supported by a number of noted figures in the life sciences, including George Church, Anthony Atala, Judith Campisi, and so forth:

http://sens.org/about/leadership/research-advisory-board

There are detailed proposals for the development of therapies involved in SENS. These can be critiqued on their details. For example, allotopic expression of mitochondrial genes can be critiqued based on what has been done, the plans for the other genes, and how it is going so far.

You are behind the times on calorie restriction research. It works very well on all measures of health in primates except for longevity. That is the big puzzle in calorie restriction: how to explain this disparity, which ties in to explaining why humans live for an unusually long time. See this paper by Fontana:

http://impactaging.com/papers/v5/n7/full/100581.html

In general calorie restriction seems better than exercise if you are going to pick one or the other, which would be foolish of course. Do both. But don't expect it will help you be one of the 25% who survive past age 90, because the only thing likely to get you there is an early implementation of SENS. Unless the programmed aging camp is right, in which case there is nothing that can be produced in time to greatly help us. But given that implementing SENS is cheap in comparison to drug development - $1 billion and 20 years to get it working in mice - what's there to lose?


"It is the building of fine bridges by Romans and Victorians in advance of material science and computer simulation."

Not really - it is the equivalent of Romans building bridges by sticking dirt together without figuring out the correct composition of building materials, why/how materials can cement, and so forth.

"allotopic expression of mitochondrial genes is absolutely a way to fix protein expression issues."

You are actively presenting bleeding edge research as a definite solution in spite of how primitive it is [1]. It is not immediately clear that allotopic expression is the answer, just because it worked in mice for one specific example it is not necessarily true that it translates to humans or other diseases. In fact, findings in mice often do not translate to humans [2].

"SENS is supported by a number of noted figures in the life sciences, including George Church, Anthony Atala, Judith Campisi, and so forth:"

While I respect Campisi's work on senescence and aging there is obviously conflict here where one of the pioneers of the field is supportive of a theory that promotes her field. For this reason I think it is best that we do not defer to authority figures on this matter as you will find reputable authorities on both sides of this debate.

"You are behind the times on calorie restriction research. It works very well on all measures of health in primates except for longevity."

See [3] from de Cabo's group (who is one of the authors on the paper in the OP). If you're talking about increasing lifespan (one of the lofty goals of SENS) is longevity not the most important thing here? From this (respected) paper de Cabo points out many flaws in the studies on caloric restriction due to differing methodologies and genetic variation that resulted in adverse effects in some murine experiments. This is far from 'working well'.

[1] http://www.genetics.org/content/165/2/707.short [2] http://www.pnas.org/content/early/2013/02/07/1222878110.abst... [3] http://www.nature.com/nature/journal/v489/n7415/full/nature1...


Why does this situation exist? I blame regulation.

It exists because you are dealing with humans. Genuinely new ideas tend to not get adopted until the old guard literally dies. They have turf to protect and it is an active disincentive to adopt new ideas, especially new ideas where you can fix things relatively cheaply and easily. There is money to be made in keeping problems alive. And people who don't understand how to fix it themselves tend to look to experts and trust their word rather than being skeptical that maybe the experts have a conflict of interest.

There is a lot that can be done currently and more simply than even your post suggests. A lot of it is "basic common sense." Studies often back up things like just eating right and exercising regularly -- which, really, people mostly don't want to do. They want a magic bullet that lets them do whatever they feel like and then magically fix the problems it creates. But Hollywood stars often already look 20 years younger than they really are and a lot of that is due to diet and exercise because their income depends in large part on their looks.

Another aspect of that is that people tend to discount damage that never occurred. So Hollywood actors and actresses who have successfully slowed the aging process instead of dramatically reversing the aging process are dismissed as not counting somehow. People tend to have a very hard time mentally counting something that was averted. It's just a very hard concept to even explain to most people. So we try to find more fuel efficient cars instead of promoting walking and public transit in part because it is easier to quantify the fuel savings and the difference in how the environment is impacted etc than if we just don't drive in the first place.

The factors involved are complex and do not boil down to regulation.

But thank you for your thought provoking comment.


For the biologically inclined, I sincerely recommend reading this paper in full. It has a number of extremely groundbreaking hypothesis, which bring together the common elements of cancer, caloric restriction, and aging.

I find it interesting that this finding suggests that free radical/reactive-oxygen-species theories of aging were close, but just off the mark. It appears that the cell can cope quite well with chemical damage of this type, but has a harder time regulating mtDNA expression, which leads to the same result: reduced mitochondria function with age.


There was also this interview with Australian ABC around the publication of the article. http://www.abc.net.au/news/2013-12-20/researchers-reverse-sy...

Apparently the video has "expired" so please refer to e.g. http://www.filedropper.com/researchersreversesymptomsofagein... for that (as an aside, I'd appreciate advice about less obtrusive file upload services)


Mr Stoyte broke the silence. 'How long do you figure it would take before a person went like that?' he said in a slow, hesitating voice. 'I mean, it wouldn't happen at once ... there'd be a long time while a person ... well, you know; while he wouldn't change any. And once you get over the first shock - well, they look like they were having a pretty good time. I mean in their own way, of course. Don't you think so, Obispo?' he insisted.

- Aldous Huxley, After Many a Summer Dies the Swan.

...But I am sure this news makes banks, bureaucracies and big pharma mega-ecstatic.


Link to the submitted article (before it was changed by an admin), for posterity's sake: http://guardianlv.com/2014/01/ageing-successfully-reversed-i...

Dunno why the submission was changed, I suspect the admin didn't actually read the article, which contains original journalism work (article writer got in touch with David Sinclair again for an additional quote).


Without being an expert in the area, but having some detailed knowledge in the field, it honestly sounds like hype. The statement that it wasn't mentioned anywhere, before is bogus. Take a look at the source [1] that describes how NAD actually has an effect on telomeres.

They really suggest using regular supplements on that url, which I'd call bullshit! I can't tell, if it's the editors fault, a missunderstandin, or if they really mean that. That's because I've no access to the real paper.

--

[1] http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleoti...


The article did not say if the mice lived significantly longer...


the great irony of cancer cells is that they themselves are immortal.. bit of poetry and sarcasm on the Creator's part.


The font size on that page is a reversible cause of ageing.


This is REALLY scary if you have recently read the following article:

Could we condemn criminals to suffer for hundreds of years? Biotechnology could let us extend convicts' lives 'indefinitely'

http://www.dailymail.co.uk/sciencetech/article-2580828/Could...

Edit: Since people have some issues with the dailymail, feel free to pick any other article on this topic:

https://encrypted.google.com/search?q=prison+life+prolonging

I just googled and dailymail appeared at the top. Not sure if that was the article i read a few weeks ago.

Also please note that I don't want to stiffle innovation in this area in any way. I think it's awesome research. But I also find it interesting to explore other "applications" of this technology.


I suspect that given the technology to halt aging, the technology to alter personality and behavior (rehabilitation) won't be far behind (and may even arrive first). The interesting questions to me are whether personalities will be criminalized along with behaviors and to what precision or degree of subtlety personality/behavior changes can be made. Too big a change and it's effectively the same as killing the person.


I would say the political/inequality ramifications are going to be foremost terryfying, unfortunately it's hard to research that beforehand.


Quoting the Daily Fail? Seems unwise. Not even going to read it and neither should anyone else.


I'm not sure why that would be?

The idea is out there... Speculating if it will happen is pointless anyways, as it will probably take a long time before reversing aging could be done on scale.

So I really don't understand the downvote(s).


The Daily Mail is like Fox News. They both carry so much stupidity and lies that it's best and much faster to just assume that they don't carry any truthful or interesting information at all. Just skip them. Not valid newssources. I'll treat anything coming from them as both lies and stupidity until proven otherwise.


Your original post is a huge tangent from the topic of discussion. That article is pure fearmongering and is exactly the type of propagandized information that stifles innovation.

Obviously it makes sense to talk about the ramifications of new technology, but the article you linked is doing this in a heavy-handed way to get people to read the article. The result is disproportionate value being placed on that idea for the average reader of dailymail, which necessarily detracts from the discussion of balance surrounding this research.


No article stifles innovation unless some idiot reads it as scripture!

Meanwhile what do you know about the average Daily Mail reader? Presumably you've researched the around 70 million readers (an exaggeration to be sure but it's a lot of people) who take a daily look at this popular newspaper. I rather think not. But that doesn't stop people like you making predictable and patronizing observations of this kind at every opportunity. No need to comment. We can all 'read' and draw our own conclusions.


I'm lumping "average daily mail reader" with average person. Surely you are not ignorant to the effects that propaganda can have on the population. The linked article does nothing but narrowly discuss one possible consequence of this type of technology in a manner meant to illicit fear or general negative association. This is by definition propaganda and it detracts from a thoughtful analysis of the larger topic of discussion. I'm not patronizing anyone by drawing attention to the idea that plenty of people use news articles as end points for information; I'm simply drawing the connection between that phenomenon and the type of biased reporting seen in the article above.




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