A handful of girls diagnosed as having 'Syndrome X' seem to defy one of the biggest certainties in life: aging. Scientists who are working to understand this rare condition say it could inform our efforts to radically extend the human lifespan:

Richard Walker has been trying to conquer ageing since he was a 26-year-old free-loving hippie. It was the 1960s, an era marked by youth: Vietnam War protests, psychedelic drugs, sexual revolutions. The young Walker relished the culture of exultation, of joie de vivre, and yet was also acutely aware of its passing. He was haunted by the knowledge that ageing would eventually steal away his vitality – that with each passing day his body was slightly less robust, slightly more decayed. One evening he went for a drive in his convertible and vowed that by his 40th birthday, he would find a cure for ageing.

Walker became a scientist to understand why he was mortal. "Certainly it wasn't due to original sin and punishment by God, as I was taught by nuns in catechism," he says. "No, it was the result of a biological process, and therefore is controlled by a mechanism that we can understand."

Medical science has already stretched the average human lifespan. Because of public health programmes and treatments for infectious diseases, the number of people over age 60 has doubled since 1980. By 2050, the over-60 set is expected to number 2 billion, or 22 per cent of the world's population. But this leads to a new problem: more people are living long enough to get chronic and degenerative conditions. Age is one of the strongest risk factors for heart disease, stroke, macular degeneration, dementia and cancer. For adults in high-income nations, that means age is the biggest risk factor for death.

Why We Age:

When Walker began his scientific career, he focused on the female reproductive system as a model of "pure ageing": a woman's ovaries, even in the absence of any disease, slowly but inevitably slide into the throes of menopause. His studies investigated how food, light, hormones and brain chemicals influence fertility in rats. But academic science is slow. He hadn't cured ageing by his 40th birthday, nor by his 50th or 60th. His life's work was tangential, at best, to answering the question of why we're mortal, and he wasn't happy about it. He was running out of time.

So he went back to the drawing board. As he describes in his book, Why We Age, Walker began a series of thought experiments to reflect on what was known and not known about ageing.

Ageing is usually defined as the slow accumulation of damage in our cells, organs and tissues, ultimately causing the physical transformations that we all recognise in elderly people. Jaws shrink and gums recede. Skin slacks. Bones brittle, cartilage thins and joints swell. Arteries stiffen and clog. Hair greys. Vision dims. Memory fades. The notion that ageing is a natural, inevitable part of life is so fixed in our culture that we rarely question it. But biologists have been questioning it for a long time.

It's a harsh world out there, and even young cells are vulnerable. It's like buying a new car: the engine runs perfectly but is still at risk of getting smashed on the highway. Our young cells survive only because they have a slew of trusty mechanics on call. Take DNA, which provides the all-important instructions for making proteins. Every time a cell divides, it makes a near-perfect copy of its three-billion-letter code. Copying mistakes happen frequently along the way, but we have specialised repair enzymes to fix them, like an automatic spellcheck. Proteins, too, are ever vulnerable. If it gets too hot, they twist into deviant shapes that keep them from working. But here again, we have a fixer: so-called 'heat shock proteins' that rush to the aid of their misfolded brethren. Our bodies are also regularly exposed to environmental poisons, such as the reactive and unstable 'free radical' molecules that come from the oxidisation of the air we breathe. Happily, our tissues are stocked with antioxidants and vitamins that neutralise this chemical damage. Time and time again, our cellular mechanics come to the rescue.

Which leads to the biologists' longstanding conundrum: if our bodies are so well tuned, why, then, does everything eventually go to hell?

One theory is that it all boils down to the pressures of evolution. Humans reproduce early in life, well before ageing rears its ugly head. All of the repair mechanisms that are important in youth – the DNA editors, the heat shock proteins, the antioxidants – help the young survive until reproduction, and are therefore passed down to future generations. But problems that show up after we're done reproducing cannot be weeded out by evolution. Hence, ageing.

Most scientists say that ageing is not caused by any one culprit but by the breakdown of many systems at once. Our sturdy DNA mechanics become less effective with age, meaning that our genetic code sees a gradual increase in mutations. Telomeres, the sequences of DNA that act as protective caps on the ends of our chromosomes, get shorter every year. Epigenetic messages, which help turn genes on and off, get corrupted with time. Heat shock proteins run down, leading to tangled protein clumps that muck up the smooth workings of a cell. Faced with all of this damage, our cells try to adjust by changing the way they metabolise nutrients and store energy. To ward off cancer, they even know how to shut themselves down. But eventually cells stop dividing and stop communicating with each other, triggering the decline we see from the outside.

Scientists trying to slow the ageing process tend to focus on one of these interconnected pathways at a time. Some researchers have shown, for example, that mice on restricted-calorie diets live longer than normal. Other labs have reported that giving mice rapamycin, a drug that targets an important cell-growth pathway, boosts their lifespan. Still other groups are investigating substances that restore telomeres, DNA repair enzymes and heat shock proteins.

During his thought experiments, Walker wondered whether all of these scientists were fixating on the wrong thing. What if all of these various types of cellular damage were the consequences of ageing, but not the root cause of it? He came up with an alternative theory: that ageing is the unavoidable fallout of our development.

The idea sat on the back burner of Walker's mind until the evening of 23 October 2005. He was working in his home office when his wife called out to him to join her in the family room. She knew he would want to see what was on TV: an episode of Datelineabout a young girl who seemed to be "frozen in time". Walker watched the show and couldn't believe what he was seeing. Brooke Greenberg was 12 years old, but just 13 pounds, and 27 inches long. Her doctors had never seen anything like her condition, and suspected the cause was a random genetic mutation. "She literally is the Fountain of Youth," her father, Howard Greenberg, said.

Walker was immediately intrigued. He had heard of other genetic diseases, such as progeria and Werner syndrome, which cause premature ageing in children and adults respectively. But this girl seemed to be different. She had a genetic disease that stopped her development and with it, Walker suspected, the ageing process. Brooke Greenberg, in other words, could help him test his theory.

Aging causes molecular changes:

There are probably a couple of dozen compounds that, like resveratrol, extend life in the lab and could be developed for human applications, says Matt Kaeberlein, a molecular biologist at the University of Washington in Seattle. The ideal outcome of these drugs, though, will not be an infinitely long life, but rather an increase in "health span", or the number of years we have before age-related disease begins. "My guess is that they would work at the level of 15 per cent increase in lifespan and a few decades' increase in health span," he says. The best-case scenario, he speculates, is that "we live to 120 but don't start to get sick until 110".

This is more profound than it may seem: if science suddenly eliminated all forms of cancer, for instance, life expectancy at birth would only increase by about three years. Implicit in Kaeberlein's argument is that ageing cannot be separated from age-related disease; it's just a matter of time before its symptoms emerge. "It's a logical fallacy to talk about curing cancer or curing Alzheimer's," he says, despite the billions of dollars that have been spent on these efforts. "The system is breaking down. Until you actually deal with the underlying problem – which is the molecular changes that are occurring during ageing – you have zero chance of curing these diseases."

Staving off these diseases – in other words, preventative medicine – is what scientists should be focused on, rather than a silly quest for immortality, says Tom Kirkwood, an ageing expert at Newcastle University. "The agenda of focusing on a life without ageing diverts much-needed attention from the real agenda," Kirkwood said in a talk at the British Science Festival last year. As the world gets older and older, research funding should be funneled into studies that help elderly people mitigate their inevitable decline. "And if, at some time in the future, that leads to a life without ageing, I would be one of the first to celebrate," Kirkwood said. "But I ain't gonna be around to see it."

Walker doesn't accept the expert consensus that immortality is scientifically impossible. But he reluctantly agrees that it's unrealistic – if not because of the science, then because of all of the social, ethical and political problems that would come with it.

There's a lot more in the article:

http://io9.com/the-mysterious-disease-that-prevents-girls-from-growing-1579101314