I can nearly eliminate cholesterol in mice (well, they start out with very little to begin with) and my roommate can cure a Huntington's disease model in his lab mice. If media attention were given to every group to achieve something remarkable in mice, we would end up hearing about a lot of false starts. And false starts are a critical/inevitable part of science, so the only thing I'm really saying is that the media attention to this topic is most likely premature.
Mice are a useful model, but they are different enough from humans that we should be cautious when interpreting mouse data in a broader context.
Once repeated studies attacking the same problem from different angles in different institutions start to align, that's when my interest gets piqued. (Unless it's research within my field, in which case I feel better able to understand the strengths and limitations of early-stage studies.)
I also admit that, to a certain extent, this is akin to a "middlebrow dismissal" (though I'm not trying to dismiss their work), and I'd love to hear from an expert in their specific domain.
Finally the truth is plain to see - humans are merely the first step to the true masters of the planet - genetically engineered immortal mice. King Dangermouse will soon take his rightful place.
In all seriousness though, curing Huntingdons or cholesterol and many other research h vectors may seem old hat to you, in the industry as it were, but for the layperson you are at a cutting edge of science benefiting all of us - take some of my perspective and you should be far more proud of your work than perhaps your comment suggests
(Of course when the mice do inherit the Earth prepare to be kept as part of a slave army)
> humans are merely the first step to the true masters of the planet - genetically engineered immortal mice. King Dangermouse will soon take his rightful place.
That was actually mentioned in a Cracked.com article yesterday
I'm going to find it hilarious when the real world goes all Assassin's Creed and our legacy to the planet is a semi-immortal, hardworking, physically ultra-tough, perfectly moral servitor race of drugged religious fanatics.
True. But a lot of studies show that enhancing telomerase activity is related to longer telomere length, which is related to lower risks of mortality and diseases. Induced in vivo gene expression is really hard to accomplish -- and you have good reason to be dubious of direct application to Homo sapiens. But one very good take away from the article is that it furthers the argument that telomerase activity is very very good for mammals. And it turns out there are some good ways of enhancing telomerase activity without inducing gene expression: exercise, stress-reduction, and a good diet.
Very nice paper from Science, "Extension of Life-Span by Introduction of Telomerase into Normal Human Cells." Similar to the article posted, but was done with cell in vitro
http://www.sciencemag.org/content/279/5349/349.short
Unfortunately, changing telomerase activity is also rather strongly linked to cancer. Still, with the dramatic improvements in cancer treatment over the last 30 years there may be a useful tradeoff where an increased cancer risk is offset by an increased heath / lifespan on average. But, don't expect a free lunch as evolution tends to find those fairly quickly.
This study "shows that it is possible to develop a telomerase-based anti-aging gene therapy without increasing the incidence of cancer," the authors affirm.
Translation: "There was no statistically significant increase in cancer detected." However, that's less meaningful than you might think as detecting even a 2x increase in cancer among mice is a lot harder than say showing in increased population lifespan.
The real question is what was their power to detect an X-fold increase in cancer. Probably quite low, as that was not the purpose of this particular study.
Heh, I worked a floor away from Dr. Szostak the year he won the Nobel. (Purely a curio, I've never met him and his knowledge didn't osmose my way.)
Call me boring, but my opinion is that telomerase activity is good until it isn't, just like everything else. However, Yamanaka's iPS work is a good reminder that sometimes manipulating a surprisingly few substances (4 proteins, in his case, leading to induced pluripotence of previously differentiated cells) is all that is needed for profound effect.
I've always been curious why mice were seen as a good filter for testing potential medications.
Isn't it just as likely that medications that seemed promising and would actually work in humans would be ineffective in mice, thus never making it to trials?
If, as you suggest, medications that work in mice don't usually work in humans, why should we expect the opposite to be true.
Of course I understand it may be the best we can do in some circumstances, but might it also be counterproductive to have such an unreliable signal?
Mice breed fast and die quick, which lets you run a lot of trials much faster than you could in humans or primates. They're also "close enough" that most treatments will have similar effects in both - most treatments that work in mice but not in humans usually fail due to bad side-effects, or due to having the same direct effect as in mice but that not causing the follow-on effects that are what is actually desired.
There are vastly more compounds and potential treatments that are harmful or do absolutely nothing than there are that are beneficial - being able to filter out nonworking treatments quickly is very important to actually finding the stuff that does work.
> most treatments will have similar effects in both
If so, that would answer the question and undercut what I was responding to.
> being able to filter out nonworking treatments quickly is very important to actually finding the stuff that does work.
Assuming that the filter is accurate. If not, we could close avenues that would be fruitful and open avenues that will be not, wasting decades and billions of dollars.
A filter doesn't need to be perfect to be worthwhile - just to pull some made-up numbers out of nowhere, if 1/100 options are worth investigating, and your filter gives you true positives 70% of the time and false positives 30% of the time, using that filter gives you about twice as much of a return on your investment as skipping the filter and investigating everything.
Of course you're right; I'm using colloquial shorthand. I'm referring to apolipoproteins bound to lipids and cholesterol (at which point we can call them lipoproteins). What I really am talking about is VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides.
awolf's challenge is particularly relevant and on-point because extremely low levels of LDL-cholesterol from birth (hypobetalipoproteinemia or abetalipoproteinemia) is associated with neurological deficits. When caused by defective APOB, it is also associated with non-alcoholic fatty liver disease.
A simple and generally correct statement: LDL particles deliver cholesterol from the liver to the cells throughout your body. Cholesterol is water insoluble, so it needs a carrier; the apolipoproteins (ApoB, which is the key protein component of VLDL and LDL) are those carriers.
>the media attention to this topic is most likely premature.
The media attention to this topic is most likely planned, not premature. The point is to get the discussion about this issue happening now, and - as you say this could possibly be a false start - but the purpose of media is to agitate the subject and motivate discussion of the issues at hand.
Its no small thing that technology to extend lifespan, who knows - 20%? - in humans, may well be within the grasp of our generation, or perhaps the next. This will be, absolutely, one of the major issues of the 21st Century if it turns out to be a real technology, applicable to the human animal.
The media are stirring this pot, and should continue to stir this pot well and truly in advance of any such achievements as giving rich, wealthy, technologically advanced societies and groups the ability to extend their life-spans, artificially ..
Just think of the consequences. Thats what the article is trying to make you do ..
Am I right in my understanding: that the reason things are easily cured in mice is that mice have "throw away" disposable soma metabolisms that don't do anywhere near as much error correction as human ones, and so there's a lot of low hanging fruit. Something badass enough to harm humans, on the other hand, has already dodged many error correction mechanisms and is intrinsically harder to fight.
To be frank, I don't know. My work with mice was rather limited so I don't have the depth of knowledge of mice as a model organism that I would need to answer this good question.
In general, toxicities are identified in humans that weren't observed in mice, the delivery mechanism may be intrinsically unsafe or unknown to be safe, the genetic architecture differs in a way that changes expression of relevant genes, or the metabolism differs in some way.
> the media attention to this topic is most likely premature
Yeah, that's true; though, I don't think there's any harm. If it piques interest in science and isn't a scam then some good comes from the attention. What better way to grab the attention of the masses than to talk about treating a fatal condition from which all humans suffer?
So this one follows on from an earlier 2008 demonstration that claimed 50% life extension via much the same method. There is some annoyance from people in the know regarding that life span claim - it was apparently not very defensible based on the data to hand.
I really need to down at least one cup of coffee before I read HN in the morning; I was surprised by the headline because I couldn't imagine someone applying something to their computer mouse to increase its lifespan. {click the headline} OH! Those kind of mice. {facepalm}
This is cool. It reminds me of hearing that tortoises don't suffer from deleterious aging[1]. I sure hope we can start expanding into space, moons, and planets before we have every John and Jane living multiple centuries.
1) Time until use in humans: 6 months to 50 years. Probably anyone's guess... Would suggest that the likely path once this research has been vetted would be to trial in medical conditions known to be associated with short telomeres such as Werner Syndrome, Ataxia Telangiectasia and others before being more widely adopted if this proved both safe and effective in humans.
2) The gene in question is conserved between humans and mice so yes, theoretically any therapy which induces telomerase in mice will do so in humans as well. [1] -
3) medically speaking the downsides are mostly 'unknown unknowns' - but some of the known unknowns are - what are the chances that the virus may integrate with the host genome? If this happens what are the chances it causes cancer? What are the risks of an immune reaction? What are the chances of mutation?
It would seem that many of these risks are not borne out by the murine trial but it would remain to be seen.
- I Should point out that (2) may convey the impression that they are upregulating the existing cellular gene to achieve this outcome: they are actually ntroducing one on the virus. In my opinion this is may be less effective than being able to eventually upregulate the gene in all cells as a virus is unlikely to get to all 10^13 (approximately, give or take an order of magnitude) cells in the human body. It could be that the 24% and 13% rates of lifespan increase (representing treatment at approximately middle age and old age respectively) may be due to the down-chain propagation of those cells that received the treatment and that more effectively delivering the virus or activating telomerase may result in better increases. However this is just my opinion and at the moment my University journal access is under maintenance so I can't read the paper
Constant telomerase activation is one of the major steps in making cancer cells immortal and thus eventually metastatic. It's possible that controlled telomerase activation (via drugs or clever future gene therapies) might present a small enough increased cancer risk that it would be worth the increased health and longevity.
Last I heard, gene therapies currently have fairly high risks involved with them (cancer, mostly).
Blasco also published in Rejuvenation Research last year about a dietary supplement that activates telomerase. So, that + this makes for some interesting reading.
Unfortunately, all of these original articles are behind a paywall. Most of us here have some University access, I believe, but not all. Science Daily at leasts gets you the gist.
I used to read Sciencedaily everyday but it's mostly unverified bullcrap reporting press release type of claims without criticism. They always report sensational discoveries but actually nothing every comes past the headlines in the actual world.
Early days, only mice so far, etc. etc. but this is pretty exciting. However ...
One of my greatest fears is that my body will outlive my brain function. Hopefully research into various forms of senility will keep pace with longevity research so I don't wind up buff and spry at 120, completely unable to recognise my friends and loved ones.
I have a family member in that state currently and it is heartbreaking to watch; I know that I'd prefer to die than live like that.
meh, just in my lifetime, I've seen the outsourcing of memorization. Would you be able to do your job without a search engine? I wouldn't.
Facial recognition (if you limit it to a limited number of faces) is already pretty good.
I mean, yeah, my cognitive abilities degrading is also about the scariest thing I can think of, too, but eh, we are developing new crutches at a reasonable rate.
Have you ever witnessed senile decay of that sort?
I mean, said family member won't be helped by something / anything like Google or a notes app on a smartphone.
She fails the three-word senility test, wherein you ask her to remember three simple words, distract her momentarily, and they're gone. Every. Single. Time. In addition, she thinks her dead husband is overseas checking out a property, doesn't recognise her grand-children, has no idea what year it is, and can't hold down a conversation.
Outsourcing of memorisation is only helpful if you've sufficient marbles left to use the tools. This sort of problem needs a hardware fix - medical, cybernetic, you name it.
I don't want to dismiss your comment. The three-word senility test is pretty hard to get over. That said, I was very impressed by the work on SenseCam from Microsoft Research. One of their original papers showed much promise in a person with a specific memory impairment. I forget the details :-p Here is the link:
yes, this is a great point. raises the issue about experience: 10 years experience? or 1 yr experience repeated 10 times. Not the same thing at all. Do you really want to extend the latter ad-infinitim as 1 yr becomes->1 day->1hour repeated N times etc
As long as you don't get Alzheimer's or some other brain-specific disease, I would think anti-aging would keep your brain as spry as the rest of your body.
The telomeres are one of the cell's natural defenses against cancer. Telomerase makes it easier for a cell to divide uncontrollably, and most cancers have activated telomerases. Despite the claims that these mice don't have increased cancer, it would be wise to exercise much caution before pursuing this kind of treatment in a human.
> The telomeres are one of the cell's natural defenses against cancer. Telomerase makes it easier for a cell to divide uncontrollably, and most cancers have activated telomerases.
These juxtaposed sentences come across as a bit contradictory. If telomeres are one of the cell's defenses against cancer, then telomerase activation should defend against cancer.
Most cancers do activate telomerase, but telomerase is not an oncogene.[1]
I thought the idea was that telomeres are like chaff that the DNA drops over the course of many replication cycles instead of losing "more important" bases of DNA. In that sense telomeres might protect against loss of function (cancers). I did not know they prevented non-homologous end joining, but see how they could. I take it non-homologous end joining could lead to gain of function (cancers).
So what is the divide? Do some people think that telomeres protect cancer?
A comment above (http://news.ycombinator.com/item?id=4846137) suggests something like this. First a cell is converted into a cancerous state, perhaps even due to a lack of telomeres and subsequent loss or gain of function. Then telomerase somehow is upregulated. If there was some error correction process (to correct the loss or gain of function cancer), could the sudden increase in telomerase and telomere length prevent that error correction from occurring?
Without telomerase, the telomeres will degrade each cell division until the Hayflick limit, where they die. So without telomerase there is a built-in limitation on the number times a cancer cell can reproduce before it dies.
It's quite simple and doesn't require any interaction with other cellular machinery.
Thanks, but it's not clear to me that cells die without telomeres or at this Hayflick limit. http://en.wikipedia.org/wiki/Hayflick_limit says they enter senescence. They stop dividing. This seems different than cell death.
That is interesting to me too though. I don't know why cells should stop dividing without telomeres, or with telomeres below a critical length. That suggests to me there is interaction with other cellular machinery at this onset of senescence.
It would be wise to exercise much caution before pursuing this kind of treatment in a human, even as part of a clinical trial. I doubt an ethics committee would approve it as part of a clinical trial of a human anti-aging treatment.
"...aging is not currently regarded as a disease, but researchers tend increasingly to view it as the common origin of conditions like insulin resistance or cardiovascular disease, whose incidence rises with age. In treating cell aging, we could prevent these diseases."
Preventing disease by preventing age could be an unending justification for prolonging life. Are there other benefits associated with this treatment? The above explanation of the research doesn't sit well with me.
Yes I mean ethically the idea of a single treatment extending life so dramatically doesn't sit well with me.
I appreciate the need to improve quality of life in old age.
People are downvoting you because they disagree with you, and not on the quality of your argument. Which I disagree with, but it's valid.
The way I'm taking it is that you think humans should live a natural life span, rather than an unnatural one boosted by a treatment, as the risk could be upheaval to our already tenuous social situation due to rising old age and supporting that. However, if a life span is extended using this treatment by a factor of, lets say conservatively 15%, and helps offset some of the illness related to ageing (heart disease etc) then that's partially resolved the situation.
There's two ways it'd go, it'd be cheap enough for many people to afford, or pricy enough for the top 10% to afford. Either way society as a whole would adapt to the change, if it's cheap and everyone can afford it then the mandatory retirement age would be lifted. We'd all be a lot healthier and we'd be capable of working longer, so pensions would take a lot longer to kick in, as would dependence on the state.
If the top 10% get it we'll have a lot of rich, long living folk doing what rich, long living folk do. Making more money. Spending more money. Society will probably adapt around that again.
It has the potential to make life on this planet untenable, but imagine what humanity could achieve if people had another 20% of time to work in. The discoveries scientists could make knowing that 20 years from being 35 they've still got chance to do another 20 year project, so fully invested in solving the problems that would take 20 years without worry it's worthless.
(I also disagree with everyone suggesting you'd be a fan of eugenics as well, as that seems out of line with that fact you seem to be a proponent of naturalised life spans)
So is your concern that the quality of life would degrade as the rate it does now (so in other words, you don't want really miserable 110 year olds). Or, are you saying, even if we extended life and kept you feeling healthy for the same proportion as now, just longer (so things were now fine and dandy until, let's say, you're 80 and then slowly degrade to 110), you would still have a problem with it?
What the researchers seem to be suggesting is extending life for no specific reason, other than preventing the complications that are associated with aging that can and do eventually lead to death.
So my issue is; there is no great societal benefit to just extending life for the sake of it, as opposed to say, making people more comfortable in their old age.
IMO the world would not benefit from millions of people living until they're 130 years old.
Screw society and 'the world', the question is have you got a damn good reason why I, as an individual, should not be allowed to extend my life if I can afford both the treatment and to support myself?
The earth is struggling to sustain the population as it is. Older people tend to require more resources for support, putting further strain on society. This is happening already in many developed countries as baby boomers enter retirement.
EDIT: PS. Thank you for not downvoting me. It's refreshing to see a difference of opinion without the vitriol
This is about making older people require fewer resources for support. The holy grail of longevity research is increased lifespan with no appreciable decline in quality of life.
The main factors that contribute to a decreased quality of life are the same ones that eventually kill us. Namely, heart disease, cancer, diabetes, and the general cognitive/motor decline that comes with aging. If we could effectively halt senescence, we'd be able to expend fewer resources on care for the elderly.
This is turning into thread soup. But for arguments sake; Surely someone with low-grade aging symptoms living an additional 30 years is going to be a greater burden on society than someone dying from complications 30 years earlier?
Are you aware that your argument also supports eugenics, sterlization of geneticaly sick people, etc?
I'd say that burden isn't as much for the whole society, as for the family of each person and for that person. And it should be the decision of person (and maybe its family, but there's controversy there) if that person wants to live longer causing this burden.
I don't think state or science should decide on such things. And it's better to at least have a choice.
>Are you aware that your argument also supports eugenics, sterlization of geneticaly sick people, etc?
No. That is hyperbole in the extreme. I'm not talking about killing people once they reach 100. Take it down a notch.
The article discusses gene therapy to change animal biology to artificially extend lifespan before the complications of age present themselves, ie. in the middle of the animals life, not after the animal has aged. I'm questioning the societal benefits of this to humans.
Interfering with telomere activity is a critical step for cancer progression (see the halmarks of cancer, limitless reproductive potential), so this procedure essentially makes every cell in your body pre-cancerous.
In my opinion, the most amazing part about this is that the way in which telomerase is delivered is via a retrovirus, typically a relative of HIV.
Since telomerase is not really an oncogene, I'm not sure that the notion of "pre-cancerous" that you're advocating has any meaning. By that token, nearly every cell is pre-cancerous, and in a fetus even more so.
Mice are a useful model, but they are different enough from humans that we should be cautious when interpreting mouse data in a broader context.
Once repeated studies attacking the same problem from different angles in different institutions start to align, that's when my interest gets piqued. (Unless it's research within my field, in which case I feel better able to understand the strengths and limitations of early-stage studies.)
I also admit that, to a certain extent, this is akin to a "middlebrow dismissal" (though I'm not trying to dismiss their work), and I'd love to hear from an expert in their specific domain.