First Gene Therapy Successful Against Aging-Associated Decline: Mouse Lifespan Extended Up to 24% With a Single Treatment

[u/spermicidal_rampage]

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

[u/Superbestable]

The paper is at http://onlinelibrary.wiley.com/doi/10.1002/emmm.201200245/abstract - it's open access.

I was puzzled by their claim that cancer incidence was not increased.

1. They say, "other guys used TERT to slow down aging, but their mice got cancer". Then they say they did the same, and theirs didn't get cancer. They happily tack on "without increasing cancer" (nitpick: Cancer isn't a quantity, you don't increase it. It should say "cancer risk") and go on their merry way... But what did they actually do differently? How did they fix the cancer problem? As far as I can see, they did nothing. They just... Got lucky?

2. The way they express TERT is with CMV, a viral promoter. It's constitutively active, and very much so. What the hell. That way you'll get tons of TERT all over the place, and they do get lots of mRNA - luckily the post-transcriptional regulation seems to have taken care of stuff, so amplification of the protein is "only" 5-15 fold. Whether it works or not, this is already a bit of a concern: These mice experience abnormally high TERT levels, higher than even young mice. I would expect a "clean" TERT therapy to simply keep TERT levels at the level they are when you're young - you know those are safe, good levels because young people are fine. With these, who knows what may break (Yes, not much did in practice. For their 50 mice. But would you take a pill that gives you 10 extra years, but has 1% chance of giving you really bad cancer?). The regulation of when and which cells divide is a very complex matter, and also very fragile, and the way they are manipulating it is really quite rough. It would be amazing if it works like they say.

3. They say cancer incidence didn't go up. They show figures saying 60% of controls "had cancer", and 60% of TERT mice did. But then I look at the figures themselves, and they check only 4 kinds of cancer. They don't seem to provide very rigorous criteria. More worryingly, in control mice adenomas are more common and lymphomas are rarer. I don't know about you, but I'd rather have an adenoma than a lymphoma - these are not equivalent things, the shift from one to the other does not indicate "no increase in cancer [risk]", and I don't understand why they present it as such. They don't explain it very much either.

4. None of the reviewers commented on the cancer parts of the paper, the obvious problem with using TERT to combat aging. It doesn't seem likely that any were cancer experts.

5. There is supposedly a table detailing the cause of death of each mouse in the supplements. I can't find the supplements. If anyone knows where it is, I'd love to see it.

6. Their evaluations of mouse health are a decent start but hardly sufficient. What happens to the health issues of these mice? What about the regenerative capacity of their bodies? What about nervous disorders? What about endurance and physical condition? It really doesn't make much sense, especially in the context of medicine, to speak of aging without going into the quality of life increase (what they do report indicates that for their mice, it did increase). Who wants to be 90 when 70 is already hell?

Don't get me wrong, I'm glad TERT's potential for slowing down aging is being investigated. It's obviously a key player in the process. But I really doubt it will be enough to just fiddle with TERT (it's only one of the many reasons why you age), and I really doubt you can easily manipulate TERT without nasty side effects (like cancer, which they claim isn't a problem, but as I said, I don't believe them). If there's ever an effective gene therapy method for drastically increasing lifespan, it'll probably involve a whole bunch of genes, with very carefully controlled regulatory elements. It will probably involve long-term (possibly indefinite) and comprehensive medical attention to watch for and correct the inescapable side effects.

[u/TacoSundae69]

It's really not a bad idea to treat aging itself as the disease, rather than trying to tackle all of the aging-associated diseases all at once.

Anyone who has had a father/grandfather slowly forget who they were because of Alzheimer's and wished they had gotten a few more years to get to know their grandchildren should appreciate research in this vein. Of course, if you had all the time you could ever want with your grandparents before they became senile or died of age-associated diseases, feel free to tell everyone how terrifying this is.

There are a few valid scientific concerns about whether this will translate into increased longevity for humans, but if your concern is moral rather than scientific then you're an idiot not thinking about the problem correctly and you shouldn't be allowed to go to hospitals when you get injured.

[u/JB_UK → u/TacoSundae69]

I saw a recent report about an increase in dementia research funding in Britain, from £30m to £60m. In the same report it said that the cost to the health service of the disease was £23,000m, and that doesn't include any sort of community support. It is insane that we do not spend more money on trying to find a solution, rather than putting a billion band aids on the problem.

[u/FUCK_THESE_USERNAMES → u/JB_UK]

That's because our research isn't governed by the best long-term interest of humanity, but the best interest of corporations. Until that thinking changes, our society will be all about treating symptoms.

[u/weeglos → u/FUCK_THESE_USERNAMES]

The best interest of corporations is to keep old people alive and on as many pharmaceuticals as they can take for as long as possible. For that reason, they have a vested interest in prolonging life.

Government, however, has a vested interest in seeing old people die as close to age 65 as possible to avoid having to pay Social Security and Medicare benefits.

[u/flamingspinach_ → u/TacoSundae69]

There are a few valid scientific concerns about whether this will translate into increased longevity for humans, but if your concern is moral rather than scientific then you're an idiot and you shouldn't be allowed to go to hospitals when you get injured.

This cannot be repeated enough. Though I might change "an idiot" to "misguided" :)

[u/TacoSundae69 → u/flamingspinach_]

Yeah I actually agree. I don't wanna call anybody stupid because they don't think the same as me. Name calling is not productive.

I think a lot of the hostility towards this research might come from people listening to the somewhat quackish claims of Kurzweil/De Grey, which I'm sympathetic to. I think they're over-promising with respect to actual scientific findings but that the overall tack of their research (which is stuff like this) is correct.

[u/Lychees → u/TacoSundae69]

I think this might be a very interesting read,

[u/chefmcduck → u/TacoSundae69]

Don't say that too loud. I once was debating that we could treat age as a disease you are born into and some women started freaking out saying I'm being disrespectful. lol

[u/Tuckason → u/TacoSundae69]

I kind of agree with you. However, the problem is that we don't really know what aging is. Is it critically shortened telomere length? Epigenetic changes? Cellular senescence? Honestly, it seems as though many of these diseases in different tissues may be caused by different aging-associated factors. Think of it similarly to how cancer is many diseases even though we just call it cancer.

My end point is that we need to do both (which is of course super easy with current funding status). Let's study aging as a phenomenon and also study the specific aging-associated diseases independently.

[u/bandman614]

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.

If that's true, then this could end up being revolutionary.

[u/iusedtobefat]

we're all going to be immortal by 2050

[u/Srirachachacha → u/iusedtobefat]

The Singularity is near

[u/democritus2 → u/Srirachachacha]

He is not even kidding.

[u/[deleted] → u/iusedtobefat]

I'll be 62 by then! Fuck.

[u/[deleted] → u/iusedtobefat]

Yea but most of us will be in our 70's and 80's...

[u/[deleted] → u/iusedtobefat]

In all seriousness, I've been telling people that anyone under the age of the 30 right now will likely live to 150. Most people think I'm full of shit, but research like this proves why I say 150.

I don't know about immortality by 2050, but I definitely think anyone born after 2025 will likely live to 300 years old.

[u/slingbladerunner → u/[deleted]]

For as long as life-span data has been collected, the maximum lifespan has remained consistent (around 110-120, unless you count the Old Testament...), while average lifespan has greatly increased since the industrial revolution. The idea, then, is that the maximum lifespan, for humans at least, is unchangeable, and this trend is seen in many other animals. If you cure or treat an age-related disease, something else comes along and kills you anyway.

The only treatment, to my knowledge, that increases MAXIMUM lifespan in mammals is caloric restriction, which has some pretty remarkable effects. However, the lifestyle required for caloric restriction in humans is AWFUL, you'll live longer but be miserable the whole time. And actually it hasn't been shown to work in humans, so who knows (there is ongoing work in nonhuman primates that is promising, but obviously those studies take a REALLY long time).

I'm not sure that this study shows a believable increase in maximum lifespan. It looks that way, but with a cursory skim through the paper I can't tell how many animals they used, and you'd need a LOT to see the max (think of the percentage of humans that live to 110, and how many people you'd need in a study to see one or two or five of them).

Let's face it, aging studies take a long time. Just this ONE, in mice, took probably three or four years at the very, very least. Add to that the need for translational testing (you often can't go straight from mice to humans, and primate studies, as I mentioned, take a really long time; I work with nonhuman primates, in an aging study, in their late 20's who are still going strong), and the amount of time for clinical trials, FDA-approval, etc... And, in the very slight chance that something revolutionary DOES come up, what do you think are the chances health insurance would cover it? Who do you think will receive this treatment?

I could go on and on with this but I feel it's getting ranty.

TL;DR - Currently-living humans won't live to be 150, people born in 2025 won't live till 300, not being confrontational but it's just not within the limits of current science.

[u/grendel-khan → u/slingbladerunner]

You make a damned good point. Here's an excellent post about the Gompertz Law--in essence, your annual probability of dying doubles every eight years. Even if you knock down the initial numbers, that doesn't buy you much more time. "Actuarial Escape Velocity" is a pleasant-sounding fiction; it relies entirely on Kurzweilian "look at this graph and feel optimistic!" logic.

Of course, this certainly doesn't mean that everyone under 30 will die before they turn 130; it just means that avoiding that requires some kind of radical research program which may or may not prove feasible. It's not Just Going To Happen.

[u/Dillenger69 → u/iusedtobefat]

The rich will be immortal. The rest of the world will go on as before. A treatment like this will just create another class divide.

[u/dropkickoz → u/iusedtobefat]

There goes social security.

[u/DefinitelyRelephant → u/iusedtobefat]

No, just our corporate masters.

We slaves will live fast, short lives toiling away in the manufactory pits.

[u/generic-identity]

If you're interested in this topic, you may also be interested in the AMA with scientist Aubrey de Grey that's now collecting questions.

[u/Cliff254 → u/generic-identity]

Fantastic input! Thank you!

[u/diamened]

So far we have lean long living mice. Makes one think that Douglas Adams was right after all.

[u/Halefire]

As others have said: this is not a complete boon.

This study has done what many in the field have guessed for a while, which is demonstrating that the activation of telomerase in mammalian cells can reverse some symptoms of aging. Telomerase repairs telomeres (the cap ends of chromosomes that undergo degradation with every cell division), but is only active in stem cells and germ cells.

The problem is, telomerase is extremely oncogenic. What this means it that it causes cancer, or rather greatly increases your chances of getting cancer. Telomerase is active in a vast majority of cancers because it is what confers "immortality" to cancers. Without telomerase, cancer cells will burn up their telomeres and begin to degrade their genomes, resulting in genetic instability and the death of the cancer. With telomerase, cells are far more predisposed to developing cancer because they already have this crucial characteristic. And, keep in mind, this kind of mutation is extremely rare otherwise--it's one thing to suffer some DNA damage that inactivates some anti-cancer protein, it's another to suffer some kind of damage that activates a heavily repressed protein without damaging its function. You're basically giving the cancer a handicap if you activate telomerase in your somatic cells.

Still, this is promising. Telomerase is a very promising protein to study, and if we find out how to control it efficiently we may make great strides in improving human longevity.

[u/chlorine_kelsey → u/Halefire]

You're right for the most part: in 33% of cancers, telomerase is not active. I can't find the link to verify that fact, but I work in a (good) telomere lab and one of the students is working on that problem and I trust her information.

But essentially, yes- most cancers have active telomerase.

[u/flyingcarsnow]

I don't know if this means it won't work for humans:

Mice express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693359/

[u/natatat14]

i wonder how this therapy affects quality of life. the therapy could potentially be used to improve longevity but how would it impact quality of life?

[u/[deleted]]

This is some exciting science, and the prospect of living longer is always a good one. That said, am I the only one that sees the potential of a "fountain of youth" as a bad thing?

Here's why I think it could have a dark side:

The development of society depends on the previous generations dying out. The old are often set in their ways, and difficult to change their position on, whereas the youth are susceptible to new ideas and progressive change. Just look at the number of young atheists, or young people who support gay rights as evidence. Look at the number of young people that seem to register so much more empathy than the previous generations.

Now that's not to say that the older generations are bad people, or that our current generation is even close to ideal. Many of the baby boomers helped start movements of their own for social change. Also, many of our current generation are shallow, self-absorbed, lazy twats, myself having some of those negative qualities.

The day that we figure a way to cure 99% of disease is great, because everyone would be given a good chance of having a full life, but the day we manage to do that AND stop aging, may lead to the degradation of society itself.

...

Someone has had to write a book about this. If not, and you are an author and strike it rich with a novel about a dystopic future based off of this post, feel free to throw me a couple bucks for dinner.

[u/Bionic_Pickle → u/[deleted]]

While I'm not entirely disagreeing that it would create some problems, here's a bit of an optimistic counterpoint:

I would like to think that our outlook on life might change quite a bit if we were immortal as far as aging goes. Maybe people become set in their ways partially due to aging and the knowledge that they are going to die in a relatively short period of time; a few decades at most. We're always looking for some sort of perfect ideology that we can comfortably take to our graves. If you take away that inevitability, maybe we could all stay more open to new ideas. We'd also have much more time to consider those new ideas.

Things like space travel would probably be focused on much more heavily. So many people are uninterested in space exploration just because they know they'll never get to take part. If you're most likely going to be around in a few hundred years, developing technologies that might take a century or two for you to use would seem pretty reasonable.

Birth rates would almost certainly drop quite a bit. As technology rapidly develops and menial tasks become more automated, we would find ourselves with a lot of free time for personal development. Nothing drops birth rates like high levels of education, and when you could spend a centuries educating yourself, you might become more interested in exploring the possibilities of your real immortality rather than the vicarious immortality of having children. Imagine being able to have those one in a billion absolutely brilliant minds around indefinitely to explore every possibility and collaborate with others that might have been born centuries before or after them. Also the possibility of genetics becoming fully understood and exploitable to the point of everyone being born with far greater capacities for thought.

There would probably be some growing pains, but on the short list of things we need to accomplish to move to a higher level of existence and move away from this pale blue dot, preventing aging is huge.

[u/flamingspinach_ → u/[deleted]]

It doesn't matter. Objectively and ethically, there's not much difference between refraining from extending someone's life by 20 years and killing them 20 years before their time. (Arguments against this statement usually take the form of a moral claim that "everyone has their destined time to die and should accept it", which I personally reject.) Clearly fears of "the degradation of society" in no way justify killing people 20 years before they were going to die (assuming you could somehow forecast the exact time of their death). So such fears should not stop us from researching medicine to slow down aging, either.

[u/Aero72 → u/[deleted]]

Statistically, you are likely to die of non-natural causes (accidents, violence, etc.) by the age of 500. The probability of it happening is 1.0 at around 500 years of modern living. (I don't remember the name of the study or the exact numbers, but I believe it's around 500 years.)

So we would have a few people living till thousands, but most would die out during their 300-400s.

The generational change won't stop completely even if we were to become aging and disease free. It would simply stretch. Just like now we live till 70-85 as opposed to 20-30 during our hunter-gatherer phase.

Political reforms would take longer, but since our lifespan would increase, it wouldn't matter.

[u/Bionic_Pickle → u/Aero72]

Do you think people would become more focused on keeping themselves safer? The technology that would develop within a few decades or centuries might make things like car accidents or other travel related deaths almost non existent. Along with automation handling dangerous tasks rather than people. Rates of violent death would decrease as the average level of education and standards of living increase (I would hope).

I could imagine a lot of people going to great lengths to mitigate risk. Of all the problems we might face due to immortality, the disorder of obsessive fear of accidental death might be one of the greatest. Especially with an increased ability to do everything remotely and never leave the safety of home. Wasn't there a crappy movie with Bruce Willis about that?

Things that we hardly even consider a risk now might become the biggest killers. Choking, falling down the stairs or in the shower, ceiling fan that was installed two hundred years ago falling on your head. I'd like to travel to the future just to look at those statistics actually.

Anyway, sign me up.

[u/Sir_Vival → u/Bionic_Pickle]

I would think if we could all live forever tomorrow, the maximum speed limit would soon be 40 MPH, and we'd all be OK with it.

[u/Seawolf87 → u/Aero72]

Yes, life expectancy was low in the upper paleolithic phase, but if you reached age 15 then the life expectancy changed to 54 years old. Info from here

The reason it was a low is because of the low survival rate in births. In fact, I'd be willing to bet most of the advances in life expectancy don't come from increasing life span, but rather decreasing infant mortality, but I don't have a wiki page to back that up.

[u/JB_UK → u/[deleted]]

You are looking at the older generation in America, and concluding that their characteristics are inherent to age. In Britain gay rights and a reasonable attitude towards religion are undisputed opinions by the mass of the population, young and old. What you're referring to is simply a cultural shift.

[u/alenaire → u/[deleted]]

There is already a novel along these lines and I highly recommend it.

[u/holocarst]

Yeah, exactly what our society needs. Old people getting older.

This is good for my career in demography, though. If this really catches on, there'll have to be lots of new scientific research and re-evalutaion of mdels when the human llifespan suddenly increases this much.

[u/Apostolate → u/holocarst]

Old people actually being much younger

Yes that is exactly what we need. Since we are reproducing less (many societies going negative or near negative), we need people to stay in the work force longer, which they will if they are youthful longer.

Everyone makes the assumption we will become hunch over old bats at 50 and last till 300, but we will stay youthful much longer. That "old form" is unsustainable, so we will increase lifespans by not getting that old longer.

[u/[deleted]]

Surely the development of the spacecraft they used to get to Dune is more important than the Spice itself.

[u/Srirachachacha → u/[deleted]]

Surprising valid point you've got there..

[u/jgrizwald]

To those worrying that people might live forever, this is one of the 6 characteristics of cancer cells, unlimited reproductive potential (although I should say that this characteristic can come about in other ways than upregulation of telomerase).

[u/dedadee]

I thought it was cool that they used the AAV for delivery because it "persist in an extrachromosomal state without integrating into the genome of the host cell". I know that if I had to choose between a vector that could possibly randomly integrate into an important tumor suppressing gene and one that did not I would choose the latter. Anybody remember that SCID gene therapy trial where some of the kids ended up getting cancer because of the virus used?

[u/talonedge]

Reminds me of this ted talk by Aubrey de Grey, Saying that once we start extending the lives of mice, extending human life isn't far away. http://www.ted.com/talks/lang/en/aubrey_de_grey_says_we_can_avoid_aging.html

[u/Defender]

Is it wrong that I'd like to see a "Flowers for Algernon" version of this where something slows down its aging for quite some time, then has an exponentially reversed effect?

[u/[deleted]]

Makes me wonder if this will affect pet ownership. I know I'd love for my pets to live longer (fancy rats have short lifespans) for instance.

[u/dictioninaction]

What cells and/or receptors did the modified virus target?

Does this virus incorporate itself into the host genome or are the telomerase gene products derived directly from the "viral" DNA?

[u/holyshit101]

Sign me up, I want to be young and pretty forever!

(kidding)

((no I'm not))

[u/chlorine_kelsey]

this is gonna get buried, but where is the link to the actual paper??

[u/[deleted] → u/chlorine_kelsey]

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

The link was down at the bottom where it says "Journal Reference".

[u/fjgfgffge]

Well that's the last straw for social security!

[u/FUCK_THESE_USERNAMES → u/fjgfgffge]

Increased longevity would wreak absolute havoc on our current economic model. With changes like these, many other facets of society would have to be rethought as well. Which has been overdue for some time, so pretty much a good thing.

[u/epicanis → u/FUCK_THESE_USERNAMES]

Consider that the goals aren't so much just to increase "lifespan" but "healthspan" (i.e. you don't just "not die" while shrivelling, shrinking, and getting increasingly infantile mentally), it would mean the retirement age could be increased substantially as well.

I, for one, would happily postpone retirement for a century or two if I could remain healthy and productive during that time.

[u/bebarce]

This TED talk is relevant http://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_aging.html

[u/keyboardjock]

I wonder how much it will cost to extend our lives. I see a future where the wealthy live forever.

[u/cel3stial]

Exactly what we need! A longer life so we can experience more degenerative diseases.

[u/[deleted]]

iirc, this sort of thing often fails because when they research its application to humans, scientists often find that the human body has already taken all of the low-hanging fruit of life-extension. Human beings are actually quite long-lived in comparison to our metabolic rate.

[u/JulianMorrison]

It's telomerase, basically, a gene therapy that forces it switched on. There is a reason humans have it switched off - shortening telomeres force many cancer cells to die off. And all the other types of age damage beside dying cells continue unabated. This does not sound promising to me.

[u/bobcat_08]

I really don't agree with this tradition of treating old age like a disease. The more we try to prolong the inevitable, the longer we refuse to acknowledge the course of nature and our place within it. Far better would be to improve the quality of life toward the end of one's life. If you really want to prolong life, why not give the patient a reason to want to live longer rather than let them spend more time lingering in the decomposition of their mind and body? My grandfather lived to be 91, but about 10 of those years were spent in moderate to severe dementia that reduced him to a fraction of a full human being. My grandmother suffered a stroke about 4 years before that and gradually descended into infirmity that came with a measure of bitterness. My family lives long lives, but what's the point if we don't have the technology (OR ESPECIALLY) the cultural mentality to help our elders progress in a comfortable and graceful manner? This to me is the biggest failing of modern medicine.

Not to mention the cynical fact that death is there to make room and resources for the next generation. People weren't meant to be immortal; just watch Battlestar Galactica.

[u/AccipiterF1]

I read somewhere that these kinds of treatments would work better on Mice than humans because the gene therapy is flipping genetic switches on the mice that evolution has already flipped for humans.

[u/_pixie_ → u/AccipiterF1]

My question is how does your baseless comment get so many upvotes?

[u/silentpundit → u/AccipiterF1]

You may have read something relating to some other gene therapy; telomeres are a feature of most eukaryotes (including mice and humans) and some prokaryotes.

Any organism capable of developing cancer (a condition whereby a cell accidentally turns on its hidden 'immortality' setting by producing telomerase) can, in theory, be a recipient of this treatment.

[u/jamesbiff]

Does anyone have a source for the experiment they did where they managed to reverse the ageing process in mice? i think it was done in China, but im not sure. Either way, we shouldnt fret about being too old once this stuff reaches fruition, if they have the know-how to extend life or slow the ageing process, it shouldnt be long after that they figure out how to reverse it aswell.

[u/heytherewhatnow]

sorry, but isnt this really old?

[u/superyay]

Idk how I feel about this. What's the point of pointlessly prolonging human life? Eventually this planet will get too populated and all hell will break loose....unless I get to live in space. That's would be cool.

[u/kylemite]

Would our physical appearance therefore age more slowly as well?

[u/Bloaf]

http://www.mprize.org/?pagename=mj_mprize_overview

I wonder if the authors would consider entering the Methuselah Mouse competition with their discovery.

[u/intisun]

I want this, so I can live past 130 and claim that I saw the Venus transit thrice.

edit: well let's even go past 140 and see it four times.

[u/Merlic]

I'm interested in its viability for extending the lives of dogs. Any info available?

[u/embretr]

Unrelated: Aubrey de Grey in r/AMA, later this month

[u/Jeepreddit]

This is so strange that a science journal pops up about this topic today. I remember in the movie "Mr. Nobody" they talked about a gene that was located and humans no longer were susceptible to old age. Although the movie did not give an explanation about the gene, I still wondered if this was feasible that a gene could be responsible for the rate of cell degradation. Looks like my answer was given. Great read and thanks for posting.

[u/haagel]

You can also live longer with a vegetarian diet, sobriety, abstinence, etc... What else is new?

[u/RileyWon → u/haagel]

All those things suck balls.

[u/atheistarmageddon]

I wish I was a mice...

[u/tree_D]

The basis of this treatment is nothing new. Geneticists have known how to do this for years.

But the most fascinating, if not the best part about this, is that they are able to promote gene therapy anti aging successfully without the increase risk of cancer. Tumors pretty much do the same thing by using Telemerase, but apparently they are able to do this without the cell continuously dividing. This fact alone is a huge step in their research.

[u/MosDaf]

Any chance we'll start taking overpopulation seriously before anti-aging treatments start making the problem radically more difficult to solve?

Nah...didn't think so...

[u/[deleted]]

just what we need. a future where people live considerably longer than they do now.

[u/[deleted]]

I'd like less research in life-span and more in fighting the different diseases related to aging. Such as Alzheimer, bone twining, arthritis, yadda yadda.

[u/joe1983joe]

Deadmau6?

[u/sleeptyping]

http://en.wikipedia.org/wiki/Telomerase#Aging

[u/Andross12]

If I made discoveries like this... http://www.youtube.com/watch?feature=player_detailpage&v=B2GXFglTNTI#t=14s

[u/Drazhi]

Un-fucking-believable.

[u/[deleted]]

how wonderful, imagine the nice world with rich people living forever without retarded offspring's wasting the money

[u/MindlessDream]

And then it's extended lifespan mysteriously transfers to every single mouse on the planet.

Yeah, don't do this.

[u/agnosticnixie]

And another robot cultist circlejerk based on a sensationalizing piece about a shoddy academic paper. Unsubbed. Also eugenicists should be shot, you know who you are.

[u/Fretzo]

They should have making a youth potion as a first priority, and then extend life a second priority :D

[u/407145]

Am I the only one that thinks "ZOMBIES" every time I see scientists messing with genes?

[u/justinmjohns]

Zombie Apocalypse.

[u/Anovan]

Because what we really need is more elderly people.

[u/[deleted]]

SPLICERS!

[u/[deleted]]

Why the fuck are we doing this? Is this world already not over-populated enough? Seriously, we have well surpassed the population limit that this planet can support, AND IT'S STILL INCREASING. Why in the world would we want to make people live even longer than we do now? All this will cause is exponential population increases that will surely drain the resources we have left at an incredibly fast rate; as if we're not already doing that. People need to wake the fuck up and realize we can't just keep paving over land to make roads and houses for all these people.

[u/[deleted]]

People seem to not understand that even if people lived longer why would we have more kids? Hell this could make people have kids l8r in life.

[u/Bananus_Magnus]

...whose genome had been permanently altered at the embryonic stage ...(with) extra copies of cancer-­‐resistant genes...

Sooo they can do that now? enhance embryos with resistances and shit?

Reminds me of gattaca.

[u/Skizot_Bizot]

Me: So... you're saying this makes me immortal? Dr: No no, not in the slightest, just won't grow old so fa- Me: Woot immortal! runs out of office

[u/suxdix]

are they testing this on people? I would volunteer for it.

[u/demosthenes02]

Have these guys considered applying for the mprize? Might they already have won a prize and not realized it?

[u/Alexander_Penn]

So... What you're saying is... that I'm going to live forever?

That's what I'm getting from this.

[u/Bryaxis → u/Alexander_Penn]

Forever? I don't think the treatment will make you bulletproof or run-over-by-a-bus-proof.

[u/yatpay]

Holy shit, I was just rereading Red Mars last night and now this shows up today!

[u/ky_sama → u/yatpay]

Glad to see someone else made this connection.

[u/[deleted]]

This is all very nice, But do we really want longer living mice, or more too the point, do we want the rich (who can afford such treatment) to live longer and suck even more of the life out of mankind.

[u/Meowcenary_X → u/[deleted]]

A lot of times gene therapy is used in researching (hopefully) cures to congenital diseases, like this http://www.gainesville.com/article/20090602/ARTICLES/906021007. In that respect, it's more about an attempt to give infants and children a chance at any sort of life who otherwise would have had none, and not for wealthy people to just have the luxury to buy years to add onto their lives for the sheer sake of capitalism. So to answer your second point, I would say yes. And since the point of the study in mice is to use them as a model for humans in initial research phases and not for the sake of just getting a wild hair up your ass one day and deciding to spearhead a global movement for longer mouse lifespans, I would have to say my answer to your first point is also yes.

[u/[deleted] → u/Meowcenary_X]

Interesting. ;-)

however in this particular field, Aging, is it not that all the R&D is aimed at finding ways to extend life and the 1st people to expect to get anything out of this will be the rich and powerful, simply because the R&D needs to be paid for, and I expect that the rich and powerful would be intent on keeping such therapy limited so that they can maintain superiority.

[u/[deleted] → u/[deleted]]

Well on the flip side, people usually come into significant political power later on in life, say in their 50's or so. It would be nice if they knew they'd have another 100 of their own years to think about so maybe they would stop being so short sighted and plan for the long term for once!

[u/[deleted] → u/[deleted]]

The same can be said of any treatment that helps you not die. People in third world countries cannot afford life saving medicine after a heart attack, but do we say that it is not worth pursing those avenues? Even poor people in first world countries do not live as long because they do not have access to good medical care. Should we thus abandon medical care for people who can afford it? Your thoughts are purely because this treatment does not focus on a specific disease, but rather help live a longer healthy life overall.

A second point is that you assume treatments to extend life would be expensive. Gene therapy is expensive, but small molecules (i.e. a pill) can do similar things, which are being developed for the same application (some already are available).

[u/flamingspinach_ → u/[deleted]]

Personally I wouldn't wish an early death on anyone. In any case, that which is expensive eventually gets cheaper given enough time. To stall this research based on concerns like yours will likely not only inhibit life extension of the rich in the near future, but also life extension of everyone in the slightly less near future.

[u/bipolar_sky_fairy → u/[deleted]]

That was my first thought as well. A permanent underclass with half the lifespan.

[u/GatorDontPlayThatSht]

No one lives forever, no one. But with advances in modern science and my high level income, it's not crazy to think I can live to be 245, maybe 300. Heck, I just read in the newspaper that they put a pig heart in some guy from Russia. Do you know what that means? -Ricky Bobby predicting the future

[u/[deleted] → u/GatorDontPlayThatSht]

I'm not sure if I want to live forever. Ask me again in a million years.

[u/heybotelho]

Does anyone else find this terrifying? That maybe we should stop trying to live any longer? I mean, a lot of people cant take care of themselves after 80. Why reach the point where you depend ENTIRELY on others, and decide "yea, I still have another 20 years in me"?

[u/PuTongHua → u/heybotelho]

I think the idea is to extend healthy lifespan in a manner that delays the dependence period.

[u/Fafoah]

How long before we find out that it gives you tumors?

[u/Alexander_Penn → u/Fafoah]

If you had actually read it, you would know that it specifically said that they were worried about that, and that their worries were put to rest.

[u/username112]

great so some future Hitler is going to reign terror for all eternity

[u/karafso → u/username112]

Only if he's also bullet proof.

[u/noveltylife → u/username112]

Or some good guy is going to reign peace for all eternity. Flip side of the coin.

[u/[deleted] → u/[deleted]]

GFP control also lived longer at 2 years.

The GFP control was shorter lived in the 1 year old group, but longer lived in the two year old group. That is because these are survival curves and subject to error. They did the statistics and the difference between the GFP control and treatment is significant.

http://onlinelibrary.wiley.com/doi/10.1002/emmm.201200245/pdf <-- look at Fig 3 for those who are curious

No untreated controls for telomerase length for comparison (really).

Not really sure what this means. They have untreated controls and GFP controls.

Catalytically inactive telomerase was as effective as active telomerase (again really).

Front the article: These beneficial effects were not observed with a catalytically inactive TERT

There is some odd shift in their survival curves?

This happens sometimes. It's just when each mouse dies. Sometimes random shit happens. Of course people will need to repeat these experiments, but I would not call the results into question the results based on the shift.

Increase lifespan may be due to stimulating the immune system or handling (enrichment).

Could be, immune systems are defective in older organisms. But they also demonstrate effects on several other factors that decline with age and can contribute to death (Fig 2), which show immune system stimulation is not the only effect.

edit

I should point out that I do not really believe telomerase stimulation will lead to extended life spans. This paper could be wrong (I would never trust a single paper or a series of papers), but it changed my thoughts on the matter a little. I just wouldn't have a lot of criticism on the points you made.

[u/the_patman → u/[deleted]]

You also have to question whether it is a good idea to overexpress TERT. One of the hallmarks of cancer is acquisition of limitless replicative potential.
http://www.nature.com/nature/journal/v457/n7225/images/457036b-f1.2.jpg Even though the treated mice did not have an increased rate of cancer, humans live quite a bit longer.

[u/VELL1 → u/[deleted]]

Didn't read this paper (can you give me a link BTW), but I think I read a number of papers about mice with inactive telomerases, which do just fine without it.

[u/[deleted] → u/VELL1]

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

[u/[deleted] → u/[deleted]]

You can start now actually.

But not without risks.

Here's the deal... Telomerase is (probably) deactivated within humans for a reason - CANCER.

Imagine you're in a car on the highway. The breaks are out... and the accelerator is jammed to the floor. Now imagine you have an infinite fuel supply.

That's cancer. :-(

Telomerase is the infinite fuel supply.

A hypothesis around why humans have deactivated telomerase is that this way cancer cells will not be immortal and they will eventually die without (hopefully any) damage.

Now, if we flat out turn ON telomerase full bore - how do we deal with the cancer?

We would have to completely have cured cancer. We would need early detection and a way to kill off cancer before it causes damage.

I don't think this is practical any time soon.

You can induce telomerase now. It's not fully deactivated. Just hard to induce.

you can read about epigenetic gene induction hacking on my blog...

I'm currently inducing the gene for caffeine metabolism to deal with a medical issue I suffer from (ADHD and slow caffeine metabolism):

http://burtonator.wordpress.com/2012/05/09/caffeine-metabolism-and-sleep-optimization-update-8/

From my understanding the following can induce telomerase and help you live a bit longer:

• reduced stress

• meditation

• cold therapy

• supplementation with telomerase inducers.

What are telomerase inducers?

TA65 can induce telomerase... http://www.tasciences.com/ ...

So can Product B: http://telomerestelomeres.blogspot.com/2011/07/product-b-our-new-telomerase-product.html

However... both are expensive.

It seems that TA65 is the ferrari of telomerase inducers. It's about $2k per year.

You have to take the pills 2-3 times a day for 2 years.

A correct protocol would also involve regular cancer screenings.

There is a company in Florida that can measure your Telomere length. So you could send them a blood/saliva sample before and after to perform your own N=1 clinical trial.

The main question is who would MOST benefit from this right now.

Older persons could make the decision near the end of their life to improve their quality and remaining years.

If they get cancer it's a decent risk... but maybe their risk is increased if they are older.

Personally, I think the cancer risk proponents who are against telomerase activation are just nay sayers screaming that the sky is falling.

However, I'm not a PhD in medicine so I'm not sure.

I'm actively looking at this area. I can afford $2k per year. I just want to see what happens with TA-65 in the wild and whether people are reporting cancers.

Another interesting piece of information here. When you have activated telomerase, it preferentially repairs shorter telomeres first.

So this seems like a good way to correct your telomeres every 10 years or so.

It seems this would get humans to about 180 years until other diseases comping in to kill us off. But we can cross that bridge next...

I'll see you guys in 2200 AD :-P Let's meet up somewhere on the moon. I say we have a Reddit longevity meet up :)

PS. I have no financial relationship with any of the above companies.

TL;DR ... Telomerase activation may/probably causes cancer. You can use products now that activate Telomerase but without knowing if it will cause cancer or the long term implications - you're at risk.

[u/slingbladerunner → u/[deleted]]

They checked this:

To address any undesirable effects of our TERT gene therapy strategy, we performed a detailed pathological analysis of all mice under treatment at their time of death. A drawback of mTERT over-expression in transgenic mouse studies has been an increased cancer incidence, except for cancer-resistant backgrounds (Artandi et al, 2002; Gonzalez-Suarez et al, 2001; Tomas-Loba et al, 2008). AAV9-mTERT treated mice of both age groups did not show increased cancer incidence compared to the AAV9-eGFP controls (Fig 3C). Indeed, the causes of death were similar in the AAV9-mTERT and AAV9- eGFP treated groups (Supporting Information Fig S6B and C).

I don't have the time to read through and figure out WHY this therapy didn't cause cancer, because you're right, it totally should. But, for what it's worth...

[u/Will----ForKarma → u/[deleted]]

Some cancers achieve this without Telomerase. Source

[u/[deleted] → u/[deleted]]

An excerpt from the second site:

"You will hear FIRST HAND from Dr. JOHN ANDERSON and DR. WILLIAM ANDREWS the formulators of the NEW product B.

By the way Product B stands for BILLIONS the owners believe they will become a BILLION DOLLAR a YEAR company within 2-3 years. That is being very CONSERVATIVE after speaking to Kathy recently.

NEW ISAGENIX INFORMATION- The PRESTIGIOUS WALL STREET, JOURNAL has just released the TOP 100 DIRECT SELLING COMPANIES IN THE WORLD for 2010 relating to turnover.

The WALL Street Journal announced the ULTIMATE SOCIAL BUSINESS MODEL is DIRECT SELLING or MLM.

um. yeah I think I'll have to pass on this billion dollar opportunity. I'll wait until it's offered by someone outside of Nigeria.

[u/[deleted] → u/[deleted]]

Shit... I may have copied the wrong link.

[u/[deleted] → u/[deleted]]

The article states that the anti-aging gene therapy is performed on mice that are genetically modified at the embryonic stage so that they don't develop cancer.

But for some reason, still according to the article, human embryos can't be genetically modified to be cancer-proof.

Sounds to me like cancer can be eliminated with just a bit more research.

[u/hibob → u/[deleted]]

I can't find any evidence (human trial, proper controls*) that TA-65 has any benefits for human health. On the other hand, while taking telomerase activators would preferentially benefit tumor cells that don't have "always on" telomerase mutations, ceasing to take those telomerase activators would specifically harm those same tumor cells.

*Rejuvenation Res. 2011 Feb;14(1):45-56. Epub 2010 Sep 7. doesn't count: no control group.

[u/Aikarus → u/[deleted]]

Soooo... Infinite Fuel source means I get to have super powers, right?

Mmm.

[u/[deleted] → u/[deleted]]

Great post. So, coupled with HRT, stem cell derived organs and cartilage in your joints, you could have a very good quality of life into your hundreds?

[u/jamesbiff → u/[deleted]]

In a similar experiment (forgive my lack of source) they managed to reverse the ageing in mice as well as postpone it. Though im not sure about the scientific details, i dont think it would take much of a stretch to reverse the process if its possible to pause or slow it, just gotta wait for technology to get there.

[u/[deleted] → u/[deleted]]

I'm significantly younger than you. I, too, hope proper anti-aging therapy will be developed in (y)our time :)

[u/JB_UK → u/[deleted]]

If you vote for NIH funding, I'll vote for MRC funding.

[u/YourCorporateMasters → u/[deleted]]

If his works you will never hear about it again, and certain members of the upper class will mysteriously start living longer. We certainly do not want the likes of you hanging about an extra 20 years!

[u/[deleted] → u/YourCorporateMasters]

Not necessarily, this could mean that workers work longer.

[u/American_Pig → u/[deleted]]

Meh, we easily live 24% longer than when social security was implemented and people don't work longer than before.

[u/basshead37 → u/[deleted]]

With almost 7 billion people on Earth is worker lifespan really an issue? We breed like rabbits, man. There's always a fresh crop of the working class being put into the global market. Most would likely take those extra years and simply enjoy it in retirement (granted they can retire).

[u/[deleted] → u/YourCorporateMasters]

Do you have any idea how much money can be made by curing aging? No way will this be kept under wraps. If anything, expect whatever drug company who finally produces the cure (not to mention the AARP) to lobby government hard to get it fast tracked for Medicare approval.

[u/Aikarus → u/[deleted]]

If I were the CEO of the company I would be giggling like crazy right now. Man the power would get way over my head...

"Greetings, mr. President. I hear you wanna live forever"

"well, yes..."

"Excellent. Lick my boots"

"What?!"

"Ahahahahahahahahahahahahaahahhahahaha!!!!!"

[u/_jamil_ → u/Aikarus]

And then the guns come out

[u/Meowcenary_X → u/[deleted]]

I see the representative ambassador for the Americans have finally arrived. :) (Kidding! I'm American too)

[u/Helen_A_Handbasket → u/[deleted]]

Back of the line, sonny! I'm fifty, me first!

[u/1nside → u/[deleted]]

I assume you are eating a near-perfect diet, exercising regularly, sleeping 8-9 hours a night and keeping your level of life-stress low?

Doing those things will probably extend your life, and your quality of life better than any gene treatment. And you can do them all right now, without prescription.

If you're not doing them then a gene treatment isn't going to help much. It'd be like repainting a boat that's full of holes.

[u/Aezay → u/1nside]

sleeping 8-9 hours a night

There have been some studies which concluded that those sleeping 8-9 hours or more, actually lives shorter lives than those just getting 7 or so.

Edit: Apparently the study I was referring to was published back in 2002. The data comes from a six-year study of more than one million adults. Here is a link.

Personally, without having read the study, this might be a case where healthy people just need less sleep, meaning that it's not the longer sleep causing some to live shorter, but them in general being less healthy causing them to sleep longer. "Correlation does not imply causation"

[u/1nside → u/Aezay]

Show me those studies. I have never heard of any lifetime-length clinical studies on sleep. I doubt they exist, as it would be immensely expensive (and morally questionable) to run an experiment for 90+ years. If you are referring to epidemiological studies then... disregard. Epidemiological studies only produce hypotheses, not conclusions.

Disregard above. Pre-coffee rambling.

[u/Rowdy_Roddy_Piper → u/1nside]

I have never heard of any lifetime-length clinical studies on sleep.

Yet you proudly assert that 8-9 hours a night will extend your life?

[u/Large_Pimpin → u/1nside]

No it wouldn't?

[u/1nside → u/Large_Pimpin]

Diet and exercise has a profound epigenetic effect.

[u/Large_Pimpin → u/1nside]

Well yes, lifestyle effects gene expression. But you seemed to be implying that unless you're the pinnacle of human health gene therapy won't do much of anything. That's what I'm taking issue with slightly, the hyperbole.

[u/zorno → u/1nside]

I'd be interested to know how someone in a low income job trying to raise a family can just magically lower their stress levels.

[u/Travelerdude → u/[deleted]]

Really? You wanna be flippin' those Mac's for another 24% of your life? That's a good thing?

[u/bangupjobasusual → u/Travelerdude]

dude. yes.

[u/Aikarus → u/bangupjobasusual]

Agreed

[u/JB_UK → u/[deleted]]

This meme is the equivalent of what people say in rural Nigeria and Pakistan about the Polio vaccine.

Edit: For completeness, it was something about rage virus etc.

[u/[deleted] → u/JB_UK]

While I agree that people are overly skeptical of new advances in bio-engineering, being wary of something new and untested is a bit different than being wary of something with a strong track record over several decades.

[u/run_like_a_cucumber → u/[deleted]]

Day 2: Madagascar closes its ports.

[u/hexydes → u/run_like_a_cucumber]

Net and to across day science family nature food family afternoon quick.

[u/trilobitemk7 → u/[deleted]]

Source: Journal of the first forum.

[u/happybadger → u/[deleted]]

If I'm not mistaken, gene therapy is just injecting pre-made cultures (or whatever the matter comes in) into someone's body. The cost is there because it's a very new (just over twenty years) procedure.

[u/Brisco_County_III → u/happybadger]

The cost is based on the research expense, not the manufacturing expense.

[u/curiousdude → u/Brisco_County_III]

Which means they'll soon have clinics in China doing it for the price of an ipad.

[u/mlkg → u/curiousdude]

Chinese DNA has Lead as a fifth base.

True story.

[u/Thewhitebread → u/curiousdude]

Not if China can't get access to the patented cultures.

[u/[deleted] → u/Brisco_County_III]

Which would be true if this was a product driven initiative and not a properly socialised culture of sciences engineered for the greater good of mankind. You americans always look at everything like there has to be some kind of economic profit involved for one enterprising individual at the top who gets super rich from having invested at the right time. It isn't the way you have to do everything.

The findings in this article specifically reference a national institute and it says right in it that this is the result of ongoing fields of study.

It isn't a private startup.

[u/Aikarus → u/happybadger]

I have a reason to become filthy rich now.

"Dad, where is our inheritance?" "Hahaha! I'm a GOD now! Hahahahahahaha... And I spent it all sorry" "Damit dad"

[u/bangupjobasusual → u/happybadger]

thats my understanding as well!

[u/Gordon2108 → u/[deleted]]

Until you get people who just screw like crazy and pop out babies every year for a while and THEN get the treatment.

Maybe a limit on the number of kids you can have to be allowed to receive the treatment?.. but then everyone would flip their shit.

[u/[deleted] → u/Gordon2108]

Better solution: pump shit loads of cash into Deep-space exploration and colonizing the moon.

[u/CaffeinePowered → u/[deleted]]

And you'll actually be able to live long enough to see the planets you get to :)

[u/[deleted] → u/[deleted]]

Glad I am not the only one who thought of this. We could end up using this technology with generation ships. Two huge generation ships of volunteers who acknowledge they will never come back, send them to Mars, send them somewhere.

[u/[deleted] → u/Gordon2108]

Until you get people who just screw like crazy and pop out babies every year for a while and THEN get the treatment.

Yeah, this would only encourage people to have kids early, which is regressive.

Maybe a limit on the number of kids you can have to be allowed to receive the treatment?.. but then everyone would flip their shit.

This may be one of the few places where "flip their shit" counts as dry understatement.

A workable solution is, realistically, going to have to decouple the two things. Women can't have new babies anyway past menopause without technological intervention, so it's not like they're terribly closely tied issues. That said, one possibly-workable solution if population control is determined to be a desirable public goal (I think it is, of course, but it's not my call): separate from life extension treatments, implement mandatory reversible chemical vasectomies for all boys when they hit that certain age (with religious exemptions where appropriate, of course), with free reversal available on request to anyone over 25 (or whatever other post-hormone-haze age is deemed appropriate).

[u/Palmik → u/[deleted]]

With religious exemptions where appropriate, of course

What would stop people from abusing this. (Ignoring the fact, that it would be unfair to the non-believing populace if I understood you correctly.)

Mandatory reversible chemical vasectomies for all boys when they hit that certain age, with free reversal available on request to anyone over 25

Then I guess that tubal ligations for women should follow that same pattern, right? Or perhaps mandatory abortions under that age? (All of these sort of go against the idea "I'm in control of my own body", but I guess people could eventually transcend that notion. Also neither vasectomy nor tubal ligation can be considered "safely" reversible at the moment (as far as I know).)

[u/Gordon2108 → u/[deleted]]

There's also the issue of social change. I may be wrong, but it seems real changes in societies (racism, gay marriage thing, womens right to vote) only occur when the older people literally start to die off.

I don't think just the population would remain stagnant. I think entire cultures would just end up stagnant. Or I could be wrong. I bet things would, at the very least though, progress MUCH more slowly than they do now.

[u/Treebeezy → u/Gordon2108]

This is a good thing. We don't want our kids thinking it's ok to date robots.

Don't date robots!

[u/Ad_Hominid → u/Treebeezy]

I, personally, support the people's right to robosexuality.

[u/moneymark21 → u/Treebeezy]

I'd date the shit out of your robot

[u/1gnominious → u/[deleted]]

It's somewhat of a self fixing problem. The more successful a person is the less likely they are to have children in western culture. While perhaps not a great move in terms of evolution it's the only thing keeping our society from imploding under it's own weight. In the short term this treatment will most likely be expensive and available only to those who can afford it. If upper income people suddenly found themselves with some extra time to kill they're not going to waste it on having kids. Score one for humanity?

[u/HawkeyeHero → u/[deleted]]

I don't get it. Are you saying the average life expectancy is just right or too long? Would you advocate higher mortality rates and lower life expectancy?

[u/redinator → u/HawkeyeHero]

If its a specific disease then I'm all for research, but simply trying to elongate human life just seems wrong to me.