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.
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)
That was actually mentioned in a Cracked.com article yesterday
Who do you think created the earth to find the Question to the Ultimate Answer?
Here's some background literature:
The Nobel Prize in 2009 was related to work in this area!
Good NEJM Review about Telomeres
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
Finally, an article from PNAS "Accelerated telomere shortening in response to life stress"
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.
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.
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?
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.
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.
"Cholesterol" is an organic compound that is essential for life. What exactly do you mean you can nearly eliminate it in mice?
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.
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 ..
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.
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?
Comments on the 2012 work here:
And here is the full paper:
This is cool. It reminds me of hearing that tortoises don't suffer from deleterious aging. I sure hope we can start expanding into space, moons, and planets before we have every John and Jane living multiple centuries.
Does the therapy used to treat the mice with these genes work with humans?
What could the possible downsides of this be (other than things like overpopulation)?
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.  -
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
Last I heard, gene therapies currently have fairly high risks involved with them (cancer, mostly).
The previous link I posted was not the one referenced in the Science Daily. That would be here:
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.
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.
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.
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.
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 = http://www.nature.com/onc/journal/v21/n4/abs/1205076a.html
I think we can all agree that telomeres are critical for preventing non-homologous end joining where it shouldn't be occurring.
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?
It's quite simple and doesn't require any interaction with other cellular machinery.
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.
We've also cured cancer in mice around 200 times already.
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.
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 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?
Yes, I hope so. How on earth is that a bad thing?
EDIT: PS. Thank you for not downvoting me. It's refreshing to see a difference of opinion without the vitriol
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.
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.
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.
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.
Learn the real science behind telomere research: http://www.sierrasci.com/?p=telomere_basics
Proof of concept: http://www.sierrasci.com/?p=proof_of_concept
Pretty impressive discovery.