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Sunday, July 12, 2009

NATURAL SELECTIONS

A teenager in an infant's body may hold the key to eternal youth


We are constantly under attack. Chemicals in the environment, ultraviolet light, even cosmic radiation — our DNA is bombarded 24/7 by agents that can cause damage and mutations. But don't take my word for it.

"It is estimated that a single cell in mammals can encounter approximately 100,000 DNA-damaging events per day," says Emi Nishimura of Tokyo Medical and Dental University, who works on the biology of aging. Given that there are something like 10 trillion cells in the human body, that's a battle on an epic scale.

Most of the DNA damage is unavoidable and fixed — being the reason, for example, why our skin wrinkles and we start to look old. But something can easily go wrong.

Nishimura's work came to mind last month after I'd digested an astonishing story about a teenage girl trapped in the body of an infant.

My immediate reaction was that the story was a hoax. I'd heard of progeria, the tragic disease that causes its child victims to age at a vastly accelerated rate. But the opposite; something that apparently freezes the aging process? It didn't seem possible.

Outside of science fiction or films such as "The Curious Case of Benjamin Button," I'd never come across the like of it. Neither, it seems, had anyone else. The case of Brooke Greenberg, from Baltimore, Maryland, is unique — and not a hoax. I read a medical report on her in a journal titled Mechanisms of Ageing and Development.

Brooke Greenberg is 16 years old, but her size and mental development correspond to that of an 11-month-old child. She has a first set of teeth, like those of an 8-year-old, but no adult teeth. Her bones have the cell structure of a 10-year-old, but are the length of an infant's. Her brain is no more developed than that of a baby.

It's an extraordinary case, and the girl's doctors can't yet explain it.

She has no known genetic disease or chromosomal abnormality. Eventually, somebody will find what's gone wrong. And what then? Could it be possible, I wondered, once we find out what is behind this arrested development, to replicate it?

Even Brooke's father has suggested that his daughter could be the "fountain of youth." Understanding her condition could allow us to switch off the aging process at any age we choose. Now we really are straying into the realms of science fiction — but that is why science is so fascinating: It allows us to understand what used to be considered supernatural.

It reminds me of the cases you sometimes hear about, of a child born in some village in a developing country with a genetic condition that is considered magical. A couple of years ago in India a girl was born with eight limbs. She was named Lakshmi after the multi-limbed Hindu goddess of wealth, and whose reincarnation some believed the girl to be. (The superfluous limbs, which were successfully removed, belonged to a "parasite twin" who had merged with the girl's body in the womb.)

Richard Walker, of the University of South Florida College of Medicine in Tampa, Florida, is Brooke's doctor. He thinks that she might help scientists discover the "master controller" of development, which seems to be switched off in her case.

A British biologist, George Bidder, proposed in 1932 that there was just such a "master controller," but that gene or those genes have never been found.

Not that we would want to switch it off completely, as appears to have happened in Brooke's case. Aging is part of life. Cells need to grow old and die, or else our bodies won't function properly. And if we couldn't grow and develop brain neurons, we wouldn't be able to learn new things, or create new memories.

However, the tragic case of Brooke Greenberg might well shed light on the mechanism of aging, and eventually allow us to turn off the bits we don't like, such as muscle deterioration, skin wrinkling, loss of stamina and sexual libido.

I haven't included hair graying in that list. Nishimura's work shows that the processes that lead to gray hair — or shiraga (white hair) as it's referred to in Japan — may have a surprisingly beneficial role.

The pigment in hair is supplied by cells called melanocytes. These cells are themselves created by stem cells, and when the number of stem cells in hair follicles decreases, hair turns gray. In tests on mice, Nishimura's team determined why the numbers of these stem cells falls.

The mice were exposed to DNA- damaging mutation agents, such as certain chemicals and radiation. In large doses, they are things that cause cancer. But what the Tokyo team found was that stem cells damaged by the mutation agents transformed themselves permanently into melanocytes — the cells that produce hair pigment. Fewer stem cells to supply new melanocytes meant that their numbers fell, and the mice turned gray.

But this is a good thing, says Nishimura. She says that the trick of having damaged stem cells turn into melanocytes might be a sophisticated way of getting rid of those damaged cells. If the mutant stem cells were allowed to continue to produce "daughter" cells, they might produce cancers.

Hair-graying, in other words, could be protecting us from cancer. I guess it's a good thing then, though I can't take too much comfort from seeing more gray hairs when I look in the mirror.

The second volume of Natural Selections columns translated into Japanese is published by Shinchosha at ¥1,500. The title is "Hito wa Ima mo Shinka Shiteru (The Evolving Human: How New Biology Explains Your Journey Through Life)."


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