A mouse that copulates until it drops dead may hold the secret to human longevity, reports Jerome Burne
When it comes to living in the fast lane, Antechinus stuartii, the Australian marsupial mouse, makes Mick Jagger look like a librarian with a lost libido.
For months before the mating season, the male’s hormone levels rise until, when it arrives, he is so bursting with testosterone and adrenaline that he fights and fornicates until he has reached a standstill. Then, plagued by stomach ulcers, and with his immune system shot to pieces, Antechinus stuartii drops dead.
Not many people know this, which is a shame, for Antechinus has much to tell us about the human condition and, in particular, about why we decay with age.
Ageing is a vexed issue these days, for the simple reason that humans are living longer. There will be 20% more people older than 65 by 2020, for example, and 1999 has been designated the United Nations year of older people. In addition, new suggestions are being made every day about effective anti-ageing fixes. Recent additions include gene therapy to boost wasting muscles, and diets of 1 800 calories.
But to produce legions of hardy octogenarians we first need to understand why we age in the first place. And that is where Antechinus, the hell-raising marsupial mouse, comes in. Antechinus, or rather, his genes, has opted to spend all his resources on competing with rivals and impregnating as many females as possible, leaving nothing for his maintenance and repair budget.
By contrast, humans follow a different approach, according to a new book on ageing by Professor Tom Kirkwood of Manchester University. Our cells and immune system go in for considerably more housekeeping, and that keeps us alive for longer, he says.
Either way, whether mouse or man, it is clear that sex and death are inextricably entwined, a point Kirkwood has demonstrated through studies of the British aristocracy. Using records that go back to AD 740, and involving more than 30 000 lords and ladies, he discovered that women who lived longer, and by implication were healthier and more hardy, were those who had fewer children.
“This was not a simple case of child- bearing women becoming worn out, because the pattern was the same for men too,” he says. “Some women’s genes devote more resources to repairing faulty cells but at the cost of being less fertile.”
This idea provides a useful framework for ageing research, and has focused scientific attention on genes involved in body repair. It also raises the issue of lifestyle. Can we encourage our bodies to improve their cellular housework and so keep us alive for even longer?
To find answers, scientists have adopted a number of approaches, of which one involves research into an inherited disorder called Werner’s syndrome. Werner’s sufferers age at about twice the normal rate so that, by their 30s, they are usually dead of heart disease, or cancer, or a defunct immune system.
The culprit, it has been discovered, is a gene involved in copying DNA. When this goes wrong, a host of problems ensue. The critical point is that the cause of Werner’s has now been pinpointed, so that it is possible to think of designing drugs to treat faulty repair mechanisms.
Another way of thinking about ageing is to look at it as if it were a form of very slow cooking. When you bake bread, proteins bind with carbohydrates to form a mixture that is soft and sticky. It is called glycosylation and a similar process seems to occur as we grow older, causing joints to stiffen, arteries to block up and the lens of the eye to become clouded by cataracts.
This process has been christened Ages, for advanced glycolisation end products, and a biotech firm, Alteon, in Ramsey, New Jersey, is working on a way to reverse it. They are developing a drug called ALT-711 described as an “Age breaker” because it is thought it might turn the clock back.
According to one report, ageing rats with heart problems had more supple arteries and more youthful skin within only three days of treatment. Recent trials, however, have not been as impressive as hoped.
In fact, the most recently touted elixirs have nothing to do with pharmaceuticals, and everything to do with lifestyle. In one case it seems that if you keep your food intake down to a joyless 1 800 calories a day for life, your body devotes more energy to repairs. The body seems to assume that if that is all the food coming in, conditions in the environment must be too bad out there for reproduction, so the best thing is to sit tight and keep our systems in good shape until there is an upturn.
And if you think that is bad, consider this notion: giving an animal a hard time – forcing it to live at a higher temperature than it prefers, for instance – also seems to prolong active life, by about 40%.
This idea is based on research on the tiny nematode worm, which has had all of its 20 000 genes mapped. Last year, Dr Gordon Lithgow, who works with Kirkwood at Manchester, found a nematode gene involved in response to stress, such as rising temperature.
“The gene involved is part of the system that controls the way the animal handles stress,” Lithgow said. “The mutation increases lifespan by making the animal produce more antioxidants and repair proteins.” Intriguingly, the same gene in humans is involved in insulin production.
However, Kirkwood is dismissive of ideas that we will soon be able to tweak genes for ageing. “There has been foolish talk of discovering genes that let you live to 200. Ageing is not some central process controlled by a conductor, it’s more like a jazz quartet, cells doing the best they can, working together but independently.”