Scientists have surprised themselves by reversing the ageing process in mice. Could they someday do the same for humans – and is it a good idea? Science Editor Dick Ahlstromand Arminta Wallace report
IF YOU WERE OFFERED the possibility of pushing back time and staying younger for longer, would you take it? Who could say no to such a proposition: no wrinkles, no painful joints, hair and stomach remaining where they were originally put? Medical science has taken another important step closer to the ambition of eternal youth, turning back the hands of time and returning youthful characteristics to ageing laboratory mice. If they can do this for mice could they do it for humans too?
Scientists from Harvard Medical School led by Prof Ronald DePinho experimented on laboratory mice to see if they could reverse signs of ageing. “We were expecting a slowing or stabilisation of the ageing process. Instead we witnessed a very dramatic reversal of their condition,” he says.
Their treatment pushed back the signs of brain ageing in the mice. They also showed that the renewal of brain tissues could bring back lost capabilities – in this case the return of a sharp sense of smell that had declined with age. They also showed that their methods could reverse tissue degeneration across a number of organs, including testes, spleen and intestine. They restored normal levels of fertility in mice that received the treatment, and even renewed their greying coats and got rid of their dermatitis.
If the method could be transferred to humans it would transform how we deal with age. Currently we have no choice: years will pass, we will age and our bodies will wear out. This research holds the promise of pushing back the final phase, extending our healthy years and perhaps allowing a gradual decline for 10 years, 20 years, perhaps longer. If it could be applied to humans “it would probably improve the health of the population over 60”, says DePinho. “That is going to take many years of research.”
All of this remains to be proven in the lab, and the scientists are nowhere near ready to attempt such a thing. They are still trying to understand the complex biochemistry going on in our bodies as we age.
We are significantly more advanced in this than 10 years ago, however, and much of the change arises because of a Nobel Prize- winning discovery made by three scientists in the US. Elizabeth Blackburn at the University of California, San Francisco, Carol Greider of Johns Hopkins University, in Baltimore, and Jack Szostak of Harvard Medical School won the 2009 prize in medicine for solving a huge problem in biology: how is it that DNA, our enormously complex genetic blueprint, can be copied so accurately time and again as our cells divide?
The answer was found to be a small repeating string of DNA at the ends of our chromosomes, a tiny structure called a telomere. Telomeres are like the plastic tips at the end of shoelaces: a simple way of preventing the lace from fraying and unravelling. Telomeres keep our chromosomes from fraying, ensuring that the chromosomes are reproduced accurately as a cell divides.
Unfortunately, the telomeres we have at birth gradually shorten as we age, eventually getting so small that they can’t do their job. This in turn opens the way for copying errors in the DNA: unwanted changes that can trigger cancers and other diseases but also bring on the physical changes seen as we age.
Telomeres and telomerase, the enzyme that forms them, are central to the work done by DePinho and colleagues. They were studying mice that were deficient in telomerase, leaving them with shorter, less effective telomeres at birth. At first the mice are fine, but after several generations the offspring begin to show signs of ageing and tissue degeneration despite being young.
The researchers wanted to see if the health of these “late generation” mice could be improved by giving them telomerase. They put them on a four-week course of the substance, and the effects were dramatic. Tissues that had shrunk and atrophied, including the testes, spleen and intestines, were improved in what the authors described as “striking tissue rejuvenation”.
The researchers then decided to study brain health, which declines in humans as we age. Treated mice immediately began to grow healthy new brain cells, bringing brain size back up to normal. The treatment also improved the covering that protects nerves, the myelin sheath. This showed the brain returning to a more youthful form, but the researchers wanted to know whether it meant the brain also worked better.
They decided to test this by measuring sensitivity to smells. Scents from predators and certain spoilt smells cause mice to avoid an area. Mice that had not benefited from the telomerase treatment did not always react to the smell, but those that had been treated saw their sense of smell restored. These mice always avoided the scents that indicated danger.
One important issue not determined in the research was whether the treatment itself could cause cancer. The mice did not develop tumours during the experiments, the researchers said, but prolonged telomerase exposure is known in some circumstances to provoke cancer growth.
Dr Aoife O’Donovan, Irish graduate and first Irish winner of a Branco Weiss research fellowship, is studying telomeres with the Nobel laureate Elizabeth Blackburn in San Francisco. “I think it is a major advance. It is kind of shocking,” says O’Donovan. It confirms earlier work linking signs of ageing with telomere shortening. The “really exciting” finding, however, is that the treatment can reverse tissue decline caused by ageing. “That really is a huge finding and has enormous implications for how we think of the clinical implications.”
This high-quality telomere research has been conducted by leading scientists in world-class institutions. They make no claims about whether this approach will be used in humans.
Unfortunately, some people seek to profit by misrepresenting this and other research into telomeres. The 2009 Nobel award is held up by numerous websites that claim to be able to treat a range of ailments by targeting telomeres. The claims are groundless: they are at best a pointless waste of money, at worst something that could cause harm, the researchers warn. It will take years for scientists to reach a point where they can say they have discovered a safe way to reverse age-related decline and enable us to grow young rather than old.
Dick Ahlstrom
'Nobody wants to expand the stage of life when we're sick and diseased'
REMEMBER THE bit in the movie ‘Cocoon’ when a bunch of old folk sneak out of a retirement home to take a dip in the swimming pool next door – and are instantly rendered younger, fitter and happier? Turns out the pool has been charged with a rejuvenating life force by visitors from another planet.
Which is pure sci-fi – or, at least, it was until this week’s announcement that scientists from Harvard Medical School have reversed the ageing process in mice by giving them injections of the enzyme telomerase.
It’s an extraordinary piece of research, not least because we can all see, immediately and in glorious Technicolor, how it applies to us. Or can we? As Dick Ahlstrom has explained in his article, experts on ageing say it’s a bit early for elixir-of-youth headlines.
Rose Anne Kenny, professor of geriatric medicine and consultant geriatrician at St James’s Hospital in Dublin, is a principal investigator with Tilda, the 10-year Irish Longitudinal Study on Ageing.
“While the Harvard work is very exciting, it’s at a very early stage – and it’s a big leap from animals, particularly mice, to humans,” she says. “The question is, if we were to give this enzyme to humans could we reverse some of the age-related changes? And the answer is, well, it’s possible.” But it might end up doing more harm than good.
“Telomeres and telomerase are also integral to the cancer cell division process, and giving telomerase may well actually increase cancers. We just don’t know. Whether this will prevent age-related diseases is also not yet clear. We don’t die of old age; we die of age-related diseases.”
But as Kenny points out, this research has implications for all areas of society. “There’s some very interesting work going on around telomere length in terms of understanding ageing and, in particular, the role of stress in ageing,” she says.
“Mothers of children with physical and mental disabilities have been shown to have shorter telomeres than mothers of the same age who don’t have children with disabilities. And we know stress is strongly associated with age-related disorders such as heart disease, lung disease and even dementia. It may be that stress is acting through telomeres and telomerase, so that’s one of the areas we’d be very interested in exploring.”
But Tilda also studies socio-economic and other matters that have an impact on the health of older people. There’s not much use looking and feeling younger if you can’t heat your home, or don’t eat properly, or suffer from depression.
“If you talk to a lot of older people,” says Eamon Timmins of Age Action Ireland, “you’ll find they don’t want to live forever. Instead, they want to live with independence and with dignity. Ireland is a deeply ageist society which doesn’t seem to have a role for older people – and whether you live for 100, 150 or 200 years isn’t going to make any difference to that.
“You and I are probably fitter and healthier than any previous generation. The question is, what do we do with that health? Do we keep on working? What role can older people play in society?”
For Prof Bert Gordijn, director of the Institute of Ethics at Dublin City University, there are some obvious ethical problems around reverse-ageing therapies. The question of whether animal models are appropriate to humans has been widely debated; there’s also a rule of thumb that says any medical treatment is acceptable only if its benefits outweigh its risks.
But such research as the Harvard study also takes us into some uncharted ethical waters. “In biogerontology – the study of the biological process of ageing – there are two goals, as I see it,” he says. “First of all, to develop ways of preventing and curing diseases of old age. That’s a perfectly reasonable goal within the range of accepted goals of medicine. The other goal is to try to expand the maximum lifespan of the human being. That’s a goal that is more problematic.”
One concern, he says, is that we might start to regard normal ageing as a medical problem rather than a natural process. Another is that huge commercial and financial interests are involved with all these medical developments – and, as we know, when commercial interests come in the door, ethical deliberations often fly out the window.
Another obvious difficulty would be around access. Would rejuvenation treatment be only for the wealthy elite or for everyone? On a planet where two-thirds of people have no access to basic antibiotics, you don’t need to be a rocket scientist to figure out the answer.
In the end, wouldn’t it show more evolutionary maturity if our species stopped chasing magic elixirs and faced up to the fact that all life forms in nature age and die?
“The oldest documented human being, in France in the early 20th century, lived to 122 and a half,” says Gordijn. “The average in the West is between 70 and 80. Is this a lifespan that allows you to have a well-fulfilled life or a flourishing life? I would say yes. So do I need to have a maximum lifespan of, say, 130 or 140? Would that enhance my chance of having a fulfilled life?”
Humans have been fascinated by the possibility of immortality for thousands of years. One of the oldest written texts unearthed by archaeologists, the Sumerian ‘Epic of Gilgamesh’, features a king who puts himself through a series of painful hoops in the hope of achieving it. “But what we don’t usually think about is, what part of life do we want to expand? Nobody wants to expand the stage of life when we’re sick and diseased.”
As for the worry that may lie behind our perennial fascination with rejuvenation, it certainly hasn’t gone away. “The fear that we’ll all die remains the same,” says Gordijn. “It doesn’t matter whether I die at 80 or at 140.”
Which makes sound good sense. Now, where did I put that jar of overpriced anti-ageing cream?
Arminta Wallace
