Harvard scientists reverse the ageing process in mice – now for humans

[tripsis]

Harvard scientists reverse the ageing process in mice – now for humans

Harvard scientists were surprised that they saw a dramatic reversal, not just a slowing down, of the ageing in mice. Now they believe they might be able to regenerate human organs

Ian Sample, science correspondent

Sunday 28 November 2010

In mice, reactivating the enzyme telomerase led to the repair of damaged tissues and reversed the signs of ageing. Photograph: Robert F. Bukaty/AP

Scientists claim to be a step closer to reversing the ageing process after rejuvenating worn out organs in elderly mice. The experimental treatment developed by researchers at the Dana-Farber Cancer Institute, Harvard Medical School, turned weak and feeble old mice into healthy animals by regenerating their aged bodies.

The surprise recovery of the animals has raised hopes among scientists that it may be possible to achieve a similar feat in humans – or at least to slow down the ageing process.

An anti-ageing therapy could have a dramatic impact on public health by reducing the burden of age-related health problems, such as dementia, stroke and heart disease, and prolonging the quality of life for an increasingly aged population.

"What we saw in these animals was not a slowing down or stabilisation of the ageing process. We saw a dramatic reversal – and that was unexpected," said Ronald DePinho, who led the study, which was published in the journal Nature.

"This could lead to strategies that enhance the regenerative potential of organs as individuals age and so increase their quality of life. Whether it serves to increase longevity is a question we are not yet in a position to answer."

The ageing process is poorly understood, but scientists know it is caused by many factors. Highly reactive particles called free radicals are made naturally in the body and cause damage to cells, while smoking, ultraviolet light and other environmental factors contribute to ageing.

The Harvard group focused on a process called telomere shortening. Most cells in the body contain 23 pairs of chromosomes, which carry our DNA. At the ends of each chromosome is a protective cap called a telomere. Each time a cell divides, the telomeres are snipped shorter, until eventually they stop working and the cell dies or goes into a suspended state called "senescence". The process is behind much of the wear and tear associated with ageing.

At Harvard, they bred genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when DePinho gave the mice injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.

"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," said DePinho.

Repeating the trick in humans will be more difficult. Mice make telomerase throughout their lives, but the enzyme is switched off in adult humans, an evolutionary compromise that stops cells growing out of control and turning into cancer. Raising levels of telomerase in people might slow the ageing process, but it makes the risk of cancer soar.

DePinho said the treatment might be safe in humans if it were given periodically and only to younger people who do not have tiny clumps of cancer cells already living, unnoticed, in their bodies.

David Kipling, who studies ageing at Cardiff University, said: "The goal for human tissue 'rejuvenation' would be to remove senescent cells, or else compensate for the deleterious effects they have on tissues and organs. Although this is a fascinating study, it must be remembered that mice are not little men, particularly with regard to their telomeres, and it remains unclear whether a similar telomerase reactivation in adult humans would lead to the removal of senescent cells."

Lynne Cox, a biochemist at Oxford University, said the study was "extremely important" and "provides proof of principle that short-term treatment to restore telomerase in adults already showing age-related tissue degeneration can rejuvenate aged tissues and restore physiological function."

DePinho said none of Harvard's mice developed cancer after the treatment. The team is now investigating whether it extends the lifespan of mice or enables them to live healthier lives into old age.

Tom Kirkwood, director of the Institute for Ageing and Health at Newcastle University, said: "The key question is what might this mean for human therapies against age-related diseases? While there is some evidence that telomere erosion contributes to age-associated human pathology, it is surely not the only, or even dominant, cause, as it appears to be in mice engineered to lack telomerase. Furthermore, there is the ever-present anxiety that telomerase reactivation is a hallmark of most human cancers."

Source.

[Auxin]

Good, I've been waiting a decade for this. Now, finally, more herbs might be tested for telomerase induction activity rather than just telomerase inhibition activity (retroviral research). Up til now I think the only known significant telomerase inducer herb traditionally used as medicine is Astragalus membranaceus, which as it happens is used to help prevent senility (and also to fight cancer, lol)

....Mice make telomerase throughout their lives, but the enzyme is switched off in adult humans, an evolutionary compromise that stops cells growing out of control and turning into cancer. Raising levels of telomerase in people might slow the ageing process, but it makes the risk of cancer soar.

DePinho said the treatment might be safe in humans if it were given periodically and only to younger people who do not have tiny clumps of cancer cells already living, unnoticed, in their bodies....

I think that statement is a bit misleading. Carcinogenesis is a multiple stage process, cells have to mutate to: divide uncontrollably, evade the immune system, and immortalize (which often involves them turning back on the telomerase in their own cells). The fear of researchers, in respect to people 'turning on' their telomerase, is that cells that have already mutated to divide uncontrollably but are not immortal could potentially be given longer life spans and thus a bigger chance to go on to immortalize through further mutations. Researchers in this field admit they currently have no way of estimating how much of a hazard this could possibly be. If further intervention is done to improve the immune systems ability to fight cancer it might not be much of a hazard at all. Once a cancer cell line has immortalized itself becoming fully fledged cancer consuming a telomerase inducer will not worsen it in any way but may improve immune system functioning.

Cant wait for researchers to test the inducer capacity of stuff like tulsi and ashwagandha.

[Magicdirt]

There are already telomerase products on the market, but at around 15 grand a year they expensive.

As far as I'm aware there is no publicly available data to prove their effectiveness in humans.

If it does turn out to be the fountain of youth I can't see it being freely available to us peasants, the ultra rich would snavvel it for themselves and it would become one of the most valuable commodities on earth.

In the meantime herbs like Gotu kola have been used for centuries to prolong life, one famous proponent of gotu kola is Li Ching-Yuen who is said to have lived to over 250 by some and closer to 200 by others Li Ching-Yuen

He said that extremes of emotion drain the Qi from your organs and he also said never to be in a rush.

Daily Qi gong was also a regular part of his lifestyle.

[Auxin]

The stuff on the market is a scam, not precisely fraudulent.. but a scam.

What they apparently did was take an herb with known telomerase inducers (Astragalus membranaceus) and identified one of the active components that was not yet patented as a stand-alone product so they could isolate it and patent it and sell it. No evidence it works better than any other component, no evidence it works better than the herb, no evidence it works in humans at all, it was simply the only way they could take a inexpensive herb and make it ridiculously expensive for rapid amoral profit to satisfy their blinding greed.

Most likely the whole herb is better than that $15,000 USD product because the various active components in the herb can work together and there may be as yet unknown active constituents in the herb. And 30 grams of Astragalus membranaceus root per day (or whatever dose your research settles you on) is much cheaper, you can even grow it.

[botanika]

In the meantime herbs like Gotu kola have been used for centuries to prolong life, one famous proponent of gotu kola is Li Ching-Yuen who is said to have lived to over 250 by some and closer to 200 by others Li Ching-Yuen

He said that extremes of emotion drain the Qi from your organs and he also said never to be in a rush.

Daily Qi gong was also a regular part of his lifestyle.

 

I'll have to track some of that Gotu Kola down! I met a lady 105 in china not long ago when I took my wife to the hospital. One problem with longevity is life can become lonely. This lady never had children so she had no family. All her closest friends that she used to play cards with at the park all died when she was 80-90.

[tripsis]

My grandfather lived to 102 with nothing out of the ordinary to keep him going so long. Can't say I care to live so long though, he called himself a "waiting statue" by the end of his life, it was very sad.

[Auxin]

I think the last couple years can be rough for most people, regardless of how long they live.

It was that way for my dad who died at 66, for my grandmother who died at 80, and for my great grandmother who died at 104. I think how many of the last years suck is more dependent on the mind we cultivate in the decades prior to that rather than just how old we grow, my great grandma really had a better end-of-life than my father because she seemed to relate to life in a genuinely better way and so was reflexively happier and more accepting of change.

It matters less to me whether I live abnormally long, and more to me that more of the last years are happier. If I had to choose thats what I'd aim for.

...of course I wouldnt mind living a happy life to the age of 104

[tripsis]

You have a very good and valid point there Auxin. I agree that one's attitude is very important towards the end of one's life. I think the thing that brought down my grandfather the most was that most of his senses were failing, so he could barely see, eliminating the ability to read, watch TV or see his friends and family, he could barely hear, eliminating the ability to have decent conversations with his family and friends, or even listen to the radio and while he maintained an acceptable level of movement for a man of his age, he still really could not do much. Hence, just waiting for it to all be over.

To enjoy a long life, I think you need to be as active as your body permits. When I see people in their 70s, 80s or 90s and they are still out there, walking in forests, gardening, etc, I have huge respect for them. I believe that with an active life in old age would naturally come an appreciation for life, as opposed to sitting in a stale living room waiting for death to come. Of course, if all your senses are failing, it would be quite limiting, but there are surely other ways to keep your mind active and occupied.

[botanika]

Walking 10km a week apparently helps keep alzheimers away when your old. Keep active and stay positive.

[Auxin]

The researchers that did those studies always admit causation was never proven. It could just be that people in the early stages of alzheimers have less tendency to walk daily, or that another factor is influencing both alzheimers and walking. Causation is a bitch to prove when to prove it you'd have to convince 40,000 people to do or not do a specific thing every day for 20 years

Walking is at least still good in other ways which are more proven, so might as well do it.

[botanika]

Walking is at least still good in other ways which are more proven, so might as well do it.

 

Exactly. Music is another good thing to keep your brain ticking. Music is one of the last things in your memory to go...plus ya know rock n roll keeps you young at heart!

[Alchemica]

Reminds me of a recent paper - making use of intensive meditation for enhanced telomerase activity and positive psychological changes.

I'm definitely not an advocate for dramatic attempts at life-extension and would prefer to see the emphasis put on enhancing global quality of life. At least the meditation training seems to be more along those lines.

I couldn't stand prolonging my life too long unless there were drastic changes to my psyche and and that of society's... I guess if steps can be taken to prevent one from dying lonely in a nursing home whilst incontinent and being tube-fed, or from suffering progressive cognitive decline, that would be a great improvement for those on the home straight.

Positive Well-Being to Higher Telomerase: Psychological Changes from Meditation Training Linked to Cellular Health

http://www.scienceda...01103171642.htm

Now, how to get positivity and meditation into a once daily pill with no side-effects?

Edited December 9, 2010 by Alchemica

[DrJohnBWatson]

Purslane may up-regulate telomere lengths and telomerase activity!

--------------------------------

http://www.ncbi.nlm.nih.gov/pubmed/17764668

Chem Biol Interact. 2007 Dec 15;170(3):145-52. Epub 2007 Jul 26.

Neuroprotective effects of purslane herb aquenous extracts against D-galactose induced neurotoxicity.

Hongxing Z, Nancai Y, Guofu H, Jianbo S, Yanxia W, Hanju H, Qian L, Wei M, Yandong Y, Hao H.

Center of Experimental Medicine, Wuhan First Hospital, Wuhan City 430022, PR China.

Abstract

In order to evaluate mechanisms of natural plant purslane herb aquenous extracts (PHAS) for neuroprotective, we assessed neuroprotective effects of PHAS at doses of 2.5, 5 and 10 mg/(kg day) on SD mice injected daily with D-gal (50 mg/(kg day)) by behavioral tests. PHAS-fed mice showed higher activity upon induction by new environmental stimuli, lower anxiety and higher novelty-seeking behavior in the open field tasks, and significantly improved learning and memory ability in step-through compared with D-gal-treated mice. We further examined the mechanisms involved in neuroprotective effects of PHAS on mouse brain. PHAS significantly increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level. Meanwhile, PHAS also could up-regulate telomere lengths and telomerase activity in PHAS-fed groups. Furthermore, we examined the expression of p21(waf1) and p53 mRNA and protein in mouse brain by western blot analysis and real-time RT-PCR. We found that p21(waf1)was down-regulated by PHAS without changing the expression of p53. The results of this study suggested that the PHAS might be a primary target of p21(waf1)and the neuroprotective effect of PHAS might be carried out through a p21(waf1)-dependent and p53-independent pathway.

----------

/ Niklas

[Mycot]

...of course I wouldnt mind living a happy life to the age of 104

 

You may well be selling yourself short. With knowledge going exponential in many fields including the medical sciences and propelled by the internet we may well be fast approaching that cusp in human history of biological immortality :- every advance creating time for the next advance.

I don't think we need fear a populuce of "waiting statues" as those extentions of lifespan will be the result of improved health. Peeps who are aprehensive about very long lifespans are generally those who accept death as a given. But what if this situation changed and changed radically and maybe even inevitably which is entirely possible with advances in the medical sciences.

Death should maybe be simply seen as a medical problem.

Edited March 14, 2011 by Mycot

[C_T]

You wouldn't say that if you worked in the medical field Mycot.

[Auxin]

People have been saying humans are on the verge of immortality since as far back as I can remember... and in that time I've watched the rise and proliferation of an unprecedented obesity and heart disease epidemic across this country. I now routinely see 7 year old girls that weigh more than me (a 31 year old male) and are well in to early puberty.

All the while the maximum age for humans has remained unchanged.

'Cusp of immortality through better pharmaceuticals' is a myth perpetuated by companies that profit most from disease.

As for the purslane study, thats pretty cool.. I hadnt seen that one. And I know just where some grows

But I'd be cautious interpreting those results. It promoted telomerase activity, yeah, but it did so in a species that already has active telomerase. We do not, the effect might not exist in us. (Tho even if it just upregulated active telomerase maybe it could be combined with something that switches telomerase on in us).

It also downregulated the mouse brain equivalent of p21. Implication there, I suppose, was that it may reduce incidence of age related neuronal apoptosis.. brain cell suicide. Thats not the biggest problem tho, when neurons age poorly they get gummed up with crud and draw in their little tendrils and stop being active neurons long before they commit suicide. In the brain p21/p53 activity and the apoptosis mechanism is far more relevant to preventing brain tumors.

Interesting direction of research (particularly re: telomerase) but I wont base any action on it without much more data.

[Mycot]

Immortality Comes to Human Cells

Gene Rejuvenates Mouse Embryonic Stem Cell Immortality

Human Immortality: A Scientific Reality?

Li Ching-Yuen

Edited March 18, 2011 by Mycot

[DrJohnBWatson]

Interesting direction of research (particularly re: telomerase) but I wont base any action on it without much more data.

 

I see you have a nice scientific scepticism.

That’s good, but I’ll try growing purslane this summer anyway and digest moderate doses over some months (to not eat to much purslane oxalic acid).

Another teleomere activator might be melatonin:

“Telomerase activity was significantly reduced in aged rats compared to young animals. Melatonin significantly increased the telomerase activity of both young and aged rats. ”

http://www.ncbi.nlm.nih.gov/pubmed/19796046

The best natural source of melatonin I’ve read about is mustard seeds.

Se page 3 in this article:

http://www.springerlink.com/content/r12145642683235q/

So, now it’s my second day on mustard.

Peace!

Niklas