The quest for the fountain of youth

There’s something about reaching 40 that’s particularly harrowing. Maybe it’s the fine lines emerging around the eyes, or the weight that settles in at the waist. Maybe it’s the sense that the indulgences granted to the young have now expired. Or perhaps it’s the knowledge that workplace age discrimination may soon be a personal issue.

If that wasn’t bad enough, there are clichés about ‘you’re only as old as you feel’, to endure, along with all those assertions that our youth oriented culture is a construct of Western media. Because, unfortunately, ageing is real.

Biologically speaking, there are good reasons why reaching middle age is a pain. Maintaining muscle mass becomes more difficult, while useful things like eyesight and hearing decline. The getting of wisdom may compensate somewhat, but it’s likely many people would willingly exchange their arthritis for a bit of youthful stupidity.

This hasn’t gone unnoticed in the scientific community and, not surprisingly, there are a number of researchers seeking the fountain of youth.

Why we age

Before age can be cured, it must be understood. Why does the human body begin to fail? The popular answer is that ageing – which is not a cause of death, but which leads to vulnerabilities that will cause death – is nature’s way of culling the population, to give the next generation some room.

Except that’s wrong. There’s no overarching ‘force of nature’ making decisions about what’s good for the species as a whole. Instead, natural selection (generally) works at the level of genes, whose mission in life is to survive by any means possible. Reproduction, in which genes can insert themselves into offspring, is how they do it. Reproduction is good, from a gene’s point of view, because the more bodies there are to carry the genes around, the greater the chance of survival.

But another survival mechanism, from the genes’ point of view, would be to maintain the body it’s in. So why don’t they? “It’s a real conundrum,” says Professor Tom Kirkwood, co-director of the Institute for Ageing and Health at the UK’s University of Newcastle. “Natural selection tends to favour things that are good and ageing is conspicuously not good for us.”

Kirkwood, who seems in fine fettle himself – he answers Fast Thinking’s queries at 6.30am from California while jetlagged – says the question occupied him for some time. “I had been working on the mechanisms that cells use to copy DNA accurately and it showed that doing things right is expensive in energy terms.”

Kirkwood says that in our primitive past, there was every chance of being injured before we could reproduce. If those injuries killed us, our genes would lose their chance of reproducing. So Kirkwood thinks that cells evolved to do everything possible to repair themselves, to maximise the body’s chance of surviving and reproducing. But keeping cells repaired is costly and difficult, so when reproduction is no longer possible – about the age of 40 – the body stops making so much effort. After all, what would be the point, if it can’t reproduce?

(This applies to male fertility as well: research from the New York University Medical Centre has shown that sperm produced by the over-40s has fragmented DNA, giving their children nearly six times the risk of autism-spectrum disorders as children born to men under 30, as well as an increased risk of schizophrenia.)

Kirkwood’s hypothesis is known as ‘the disposable soma theory’. In searching for evidence to support the idea, he and Dutch colleague looked at European birth records over 1200 years. They chose the birth records of aristocrats, partly because such records exist, and partly because they could be sure that the mortality they saw wouldn’t be caused by poverty. “In aristocratic families, there was always pressure to have an heir, so people would try pretty hard to produce the next generation,” says Kirkwood. Despite this, the records showed “a relationship between higher longevity and lower fertility.”

In other words, the slower a body is to reproduce, the longer it seems to last. Another piece of evidence that seems to support Kirkwood’s hypothesis is that a restricted calorie diet seems to delay the ageing process in mice. It’s thought that a class of proteins, nicknamed ‘sirtuins’, is behind this, and there is a now a race to find drugs that mimic their actions. “The speculation has been that calorie restriction shuts down fertility,” says Kirkwood. “Perhaps when humans are exposed to famine, you shut down and make a big energy saving. Maybe some of the energy you’ve saved goes into maintaining the body, with the hope that when things get better you can reproduce.”

Does that mean people who don’t have children will live longer? “These things are set in the genome. We have a particular disposition and you can’t trick it.” No, in other words. However, Kirkwood does believe that “we will probably see natural selection push back the age of menopause and that will perhaps go hand in hand with increases in longevity.”

An anti-ageing pill

Dr Aubrey de Grey is the kind of scientist other scientists love to hate, because he doesn’t hedge his claims with qualifications, the way other scientists do. He just comes right out and says that ageing’s days are numbered. “There is probably enough known about the process for us to be able to explore very realistic, feasible approaches to doing something about it,” he says.

De Grey started as a computer scientist, before going into artificial intelligence. In 1995, he began to read the literature of gerontology (the science of ageing) and later wrote a groundbreaking, theoretical paper speculating about the accumulations of mutations in mitochondria, the cell’s powerhouses. Cambridge University awarded him a PhD in biology, despite his lack of lab work, and today he is the chief officer of the Methuselah Foundation, a US organisation dedicated to curing ageing.

In de Grey’s view, ageing is caused by seven types of cellular damage, including mutations, cell loss and the inability to get rid of toxic waste. His plan to defeat ageing is called Strategies for Engineered Negligible Senescence (SENS). “Essentially the approach I propound is a repair and maintenance approach.”

He uses a car analogy, saying that over time, simply keeping a car polished and clean isn’t enough. Eventually, the parts need to be replaced. “In the case of the human body, we may end up doing quite a bit of what we need to do by transplantation, but by and large it will be replacement of parts at the molecular level and cleaning out the garbage,” which will stall or reverse ageing, he suggests, adding that a lot of promising research is focused on stimulating stem cells to repair organs that are not working so well. “We’re getting pretty good at taking cells in one particular state and manipulating them into a different state.”

Without cellular decay, and the diseases that come in its wake, old age would be a healthy, productive time. De Grey even suggests people could be restored to a biologically younger state. Old age and all its unpleasant consequences would be consigned to the dustbin of history – at least for the people who can afford the treatment.

But if people don’t die, and they continue to reproduce, how will everyone fit? “There will be three options,” says de Grey. “We simply don’t use the therapies because we prefer not to have overpopulation. Option two is we decide that suffering and death is really very serious and we’re willing to put up with fewer children, because the people who are alive are more important.” Option three is to cross fingers and hope that technology can sort things out.

The sceptics

The gerontology community, by and large, don’t have a lot of time for de Grey. Dr Rich Miller, a highly respected gerontologist from the University of Michigan, even wrote a sarcastic open letter to de Grey in 2005, asking him to suggest ways that bio-engineering could create flying pigs. On some basic points, though, the two men agree. “The answer on stem cells is a definite ‘maybe’,” says Miller. “We don’t know what stems cells are good for and what causes ageing. It’s a reasonable guess that maybe replacing or fixing up those stem cells might be a good thing to do.”

He also agrees that some damage can be reversed. “If you break a bone, the bone can be fixed. The general issue of whether global change can be reversed is much trickier, but in fruit flies there is some evidence the answer might be yes.”

And like de Grey, Miller becomes impatient at the doomsayers who worry that research into old age might have devastating consequences. “There is an irrational public predisposition to regard research on specific late-life diseases as marvellous, but to regard research on aging… as a public menace bound to produce a world filled with non-productive, chronically disabled, unhappy senior citizens consuming more than they produce,” he wrote in The Millbank Quarterly.” It does little good to point out that a similar argument could have been made 200 years ago against penicillin, plumbing systems and surgical anaesthesia, each of which helps produce people who remain productive and healthy to the age of 40, and sometimes even beyond.”

Miller even believes much research money is wasted on studying specific diseases of ageing, like Alzheimer’s, rather than on ageing itself, the root of nearly all cancers and late-life illnesses. The reason, he says, is because diseases like diabetes have lobbyists looking after them. Yet his research is promising: “We’re trying to figure out what makes cells resistant to stress. We have some enzymes that, when you apply them to mice, they begin acting like young mice again.”

But where Miller does not agree with de Grey is the idea that ageing can be reversed completely. “We are negative four thousand years away from that,” he says, because the problem is too complex, and the amount of cellular damage a human being accumulates in an average life is too great. He does, however, believe that what science will ultimately offer is the possibility of extending life spans by 30% to 40% and keeping people healthier to the end of their life.

And that’s it.

Well, if there’s no possibility of a youth pill, where are scientists up to on the other indignities of ageing – sagging skin and floppy stomachs? Miller says the answer has been known for a long time: “Weights. Ageing typically results in muscle wasting and you can put that off by doing weights.”

He also suggests staying out of the sun. Which is another way of saying: botox or bust.

Felicity Carter

This article originally appeared in Fast Thinking magazine in 2008.

 

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