Telomerase – Mouse lifespan extended up to 24% with single treatment (May 2012)

http://www.sciencedaily.com/releases/2012/05/120514204050.htm

by evo_9 • 14 years ago

177 89 14 years ago

sciencedaily.com

RandallBrown• 14 years ago

Assuming no major side effects how long before something like this can be used in humans? What are the next steps even?

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)?

kenthorvath3• 14 years ago

Blasco also published in Rejuvenation Research last year about a dietary supplement that activates telomerase. So, that + this makes for some interesting reading.

http://online.liebertpub.com/doi/abs/10.1089/rej.2010.1085

dreamdu5t• 14 years ago

Much better than the science daily article. Thank you!

woodchuck64• 14 years ago

Hmm.. $220 for 30 pills: http://ta-sciences.com/cgi-bin/xflow/shop.cgi?catid=0&us...

robbiep• 14 years ago

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

[1] http://www.ncbi.nlm.nih.gov/sites/homologene/31141

grey413• 14 years ago

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).

reasonattlm• 14 years ago

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.

Comments on the 2012 work here:

http://www.fightaging.org/archives/2012/05/telomerase-gene-t...

And here is the full paper:

http://onlinelibrary.wiley.com/doi/10.1002/emmm.201200245/fu...

zone411• 14 years ago

Caloric restriction also greatly extends life span in mice (http://www.ncbi.nlm.nih.gov/pubmed/3958810) but it hasn't translated into monkeys (http://www.nature.com/news/calorie-restriction-falters-in-th...).

Camillo• 14 years ago

Interesting! I'm actually trying to eat a hypercaloric diet to increase my weight at the moment, and that's one less thing I have to worry about.

pebb• 14 years ago

All the side effects are positives. The side effect we wants.

freddealmeida• 14 years ago

My first thought was to my desktop mouse. lol.

Pretty impressive discovery.

qq66• 14 years ago

Mine too -- then I thought -- I've never had an optical mouse break on me, why would I need this? :)

bluedanieru• 14 years ago

There has never been a better time to be a mouse.

etherspin• 14 years ago

24% more time spent being experimented on before your cancer ridden or organ failing demise !

michaelhoffman4• 14 years ago

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.

kenthorvath3• 14 years ago

That's what clinical trials and FDA approval is for (at least in theory).

michaelhoffman4• 14 years ago

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.

carbocation9• 14 years ago

> 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]

1 = http://www.nature.com/onc/journal/v21/n4/abs/1205076a.html

michaelhoffman4• 14 years ago

Specifically I meant what many would regard as one of the telomeres' fundamental characteristics: their limited nature.

xenophanes• 14 years ago

What is the argument the mice were living a percentage longer instead of a roughly fixed amount of time longer?

DigitalSea• 14 years ago

"Want longer lasting life? try new LifeExtend from Bayer Pharmaceuticals coming soon to a pharmacy near you"

andrewfelix6• 14 years ago

"...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.

tolmasky2• 14 years ago

Are you against preventing aging? (Just wanting to clarify what you meant by "doesn't sit well with me")

andrewfelix6• 14 years ago

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.

orangecat• 14 years ago

Preventing disease by preventing age could be an unending justification for prolonging life.

Yes, I hope so. How on earth is that a bad thing?

andrewfelix6• 14 years ago

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

qiqing• 14 years ago

The rate at which therapies effective in mice translate to humans is surprisingly low.

We've also cured cancer in mice around 200 times already.

thisisnotmyname• 14 years ago

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.

carbocation9• 14 years ago

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.

carbocation9• 14 years ago

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.

nine_k• 14 years ago

Isn't telomerase-based aging mechanism more or less the same in all mammals?

awolf• 14 years ago

> I can nearly eliminate cholesterol in mice

"Cholesterol" is an organic compound that is essential for life. What exactly do you mean you can nearly eliminate it in mice?

carbocation9• 14 years ago

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.

leoh• 14 years ago

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.

Here's some background literature:

The Nobel Prize in 2009 was related to work in this area! http://www.nobelprize.org/nobel_prizes/medicine/laureates/20...

Good NEJM Review about Telomeres http://www.nejm.org/doi/full/10.1056/NEJMra0903373

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

Finally, an article from PNAS "Accelerated telomere shortening in response to life stress" http://www.pnas.org/content/101/49/17312.short

Enjoy!

carbocation9• 14 years ago

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.

Retric2• 14 years ago

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.

lifeisstillgood3• 14 years ago

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)

stinky6133• 14 years ago

> 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

http://www.cracked.com/article_20090_6-creepy-things-you-nev...

bitwize2• 14 years ago

Finally the truth is plain to see - humans are merely the first step to the true masters of the planet - genetically engineered immortal mice.

Who do you think created the earth to find the Question to the Ultimate Answer?

eli_gottlieb• 14 years ago

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.

primitur• 14 years ago

>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 ..

aneth42• 14 years ago

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?

jbri2• 14 years ago

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.

JulianMorrison• 14 years ago

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.

carbocation9• 14 years ago

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.

stinky6133• 14 years ago

> 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?

pasbesoin• 14 years ago

Out of curiosity, any observation (casual or formal) of what happens to neural health when you eliminate cholesterol?

kingkawn• 14 years ago

most people's lifespans are currently not long enough for telomerase activity to make a meaningful impact on their cell longevity.

duncan_bayne2• 14 years ago

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.

lsc• 14 years ago

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.

duncan_bayne2• 14 years ago

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.

DennisP• 14 years ago

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.

someperson• 14 years ago

[May 2012]

hayksaakian• 14 years ago

I thought this was about making my computer mouse last longer based on the title and context of hacker news.

ommunist• 14 years ago

What about the cats?

bitL• 14 years ago

It's good to be a mouse nowadays!

bjhoops1• 14 years ago

Treatments with "DNA-modified virus"? Looks like we're one step closer to the Zombie Apocalypse!

stinky6133• 14 years ago

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]http://io9.com/5618046/the-mystery-of-why-turtles-never-grow...

ceej• 14 years ago

Lots of misguided and misinformed comments on this topic.

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

Telomerase – Mouse lifespan extended up to 24% with single treatment (May 2012)

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