50% Maximum Life Extension in Mice Via p53 and Telomerase

My attention was drawn to a Spanish article on one of the many research groups investigating the role of p53 in aging and cancer. There has been a great deal of interest in finding ways around the "cancer or aging, choose one" limitation to this set of biochemical mechanisms, thought to apply until recently. This Spanish article is somewhat in advance of the scientific publication; I'm not sure why that is the case.

The translation via Google is fair (suggestions taken on a better translation automaton):

In this line, Serrano said that the genomes of a chimpanzee and humans are virtually identical at 99.8%. However, the maximum life of a chimpanzee is 60 years and the human rarely exceeds 110. The average of a chimpanzee is 40 years and that of a human, 80. There must be something in our genes very subtle changes made to live 50 years to live 100. Then, along with the team of Mary Blasco, we are going to make some genetic manipulation to see if we can increase longevity in mice much more. That is our challenge If we get a mouse in the privileged environment of a laboratory comes to live three years to live six passes, it would be proof that longevity is flexible and would know how to enlarge it.

So it seems compelled to ask the molecular biologist in this battle if they have undertaken together against cancer and aging, it is just a matter of putting telomerase a mouse to make it immortal. The answer is no, because telomerase makes more cancer. To ensure a tumor, which has activated telomerase, and if a mouse has more telomerase than normal, for example, on transgenic mice, we know that you have more tumors. What we have done is to use the superratones Manuel, because p53 protects cancer and a 18% lengthens the life of mice, and if we add to this the gene of immortality, telomerase, which got these mice [to] live an average of 50% more, without cancer, which are words older. That is what we have discovered now.

Because this extension of life, 50% in superratones is the longest that has been described in mammals.

You get the gist, despite the breakdown of translation in the last few sentences: there are combinations of metabolic and genetic states in mammals not selected for by evolution that nonetheless lead to a clearly superior beast, from our perspective at least. Well, more or less. If you head over to the Methuselah Foundation forums, you'll find that Michael Rae wrote a long piece on this research back in mid-2007, before the life span studies were complete:

The standard reading is that the "Super p53" mice are getting less cancer, but are having their [life spans] restrained by lack of tissue replenishment due to stem cell loss, while the telomerase transgenics are on the opposite horn of the same dilemma. It seems at least possible that if one overlaid the strong cancer resistance conferred by the former, with the increase in stem cell mobilization and proliferative capacity of the latter, you'd wind up with a long-lived, slow-aging mouse.

There are a lot of caveats and details both prior and after that statement, many of which still apply even with these final life span study results. It's not all completely clear-cut, as is often the case, but I can see this impressive work garnering a great deal of attention in the popular press once it jumps the language gap for the English-speaking world.



This via BabelFish ( http://world.altavista.com/tr ), plus a small amount of obvious reconstruction on my part:

So it seems necessary to ask the molecular biologist if, in this battle that they have undertaken jointly against the cancer and the aging, it is only a question of putting telomerase into a mouse to make it immortal. "The answer is no, because telomerase causes more cancer. So that there is a tumor, it must activate telomerase, and if a mouse has more telomerase than the normal thing, for example, making transgénic mice, we know that it will have more tumors. What we have done is to use the Manuel [Serrano's] supermice, because p53 protects against cancer and extends life of the mice 18%, and added the gene of immortality, telomerase, and we obtained that these multitransgénic mice live an average on a 50% more, without cancer, which is greater words. That is what we have discovered now ".

Greater words. Because this prolongation of life, of 50%, in the supermice is longest that has been described in mammals. More than what it is obtained with caloric restriction, that is one of the most important mechanisms to extend the life. "We have still not been able to make immortal mice, which means that probably there are more things, and this is the next step. This is the first time that reveals an effect of telomerase in the longevity. In no organism, neither worm, nor leavening, had this been seen, except in cells ", assures Blasco, without hiding his satisfaction.


Posted by: Michael at January 29th, 2008 4:29 AM

Immortality is just not very evolutionarily useful, but we'll probably figure out how to program it within a century or so. It's probably not even that complicated compared to many naturally evolved capabilities.

Posted by: TallDave at January 29th, 2008 11:30 AM

"In no organism, neither worm, nor leavening, had this been seen, except in cells"

leavening = yeast?

Posted by: newscaper at January 29th, 2008 2:02 PM

They should combine this with other lifespan extending genes(e.g. CR related). It would be interesting to see how far they could push their lifespan.

Posted by: darian at January 31st, 2008 5:21 AM

What's interesting is, reading the original linked article is that unlike previous experiments it seems increased amounts of p53 alone lengthened lifespan by 18%, if I'm reading it right.

It would also be very nice to see what would happen if the supermice implemented calorie restriction with intermittent fasting. Since I've heard such vastly boost antioxidant capacity and upregulate autophagocytosis, it should complement the enhanced p53 and telomerase by reducing damage and repairing it faster.

Posted by: Darian Smith at October 27th, 2011 8:52 AM

The more interesting point is that the U.S. government ran Telomolecular out of business 5 years ago allegedly for fraud. Telo was delivering p53 (and other tumor suppressors) and telomerase protein to cells in nanoparticles to fight cancer and aging. If this Spanish study is right then Telo had a real treatment for aging years ago. The CEO was lynched by the government that argued it was bogus science, even though the patents look really strong. I think there is a trial coming up soon on this and it will be interesting to see if the government wins or if it was persecuting innocent scientists again.

Posted by: ScienceDude at December 27th, 2011 6:04 PM

Our 62 yr research in JNMA 2001,94;490-493 proves that P53 gene and complex network is stabilized and optimized in preventing all forms of cancer and achieving max lifespan only when serum albumin >4.6% (>52g/L is best). This explains why Bowhead Whales live >200 years without cancer and signs of aging ( NHF 2009) cells grown in 52g/l comparable to serum levels last =200 yrs and none mutate to cancer lines. The NCI and NIA were sent my findings for many yrs yet failed to inform the public. Shame

Posted by: kenneth Seaton D.Sc at April 23rd, 2013 11:39 AM

Fascinating. What would be much more important for those of us already alive would be if researchers would take mice that are already old and then at that point use gene therapy to kick up their telomerase and p53 activity, or at least create transgenic mice where the genes regulating that activity could be "flipped on" once they're already older. That would more closely model therapies we humans (who are of course not born transgenic) could use someday.

I also wonder if a telomerase therapy would be something like rapa where an organism would still get most of the benefits getting it when they're already old, or if instead it's more like CR where there's limited benefits of getting at an old age.

Posted by: J at October 27th, 2014 1:42 PM

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