What price for a longer life?

Manipulating DNA and even starving our bodies are touted as offering a longer life, but what are the legal, social and ethical implications?

Most people want to live longer, but would you want to live to 1,000? Researchers studying the genetics of ageing believe that living for a millennium is possible, but also wonder who in their right mind would want to stick around for so long.

And if we all had the option what would a planet full of Methuselahs mean in terms of food, water and energy supplies? Could society cope with so many people hanging about for so many years?

Scientists are busy chasing the Methuselah gene, the secret of long life that many believe lies hidden in DNA, our genetic blueprint.

But is equal effort going into studying the legal, social and ethical questions thrown up by this research? What are the implications of discoveries made in the science of immortality, and does anyone really care so long as they get a chance to stick around that little bit longer?

Researchers around the world are studying the ageing process in an attempt to understand why some of us check out at 50 or 60 years while others manage 120 or even 130. Most of the effort is focused on looking for differences in our DNA and also on changes in small pieces of DNA known as telomeres.

Another body of research looks at enduring a calorie restricted (CR) diet as a way to squeeze more years out of life. This work is based on findings dating back to the 1930s which showed that it was possible to extend the life of various species by reducing their calorific intake. This was quantified more than a decade ago with research from Washington University indicating lifespan in mice increased by up to 30 per cent under a CR regime. More recent work has pushed this to two and even three times normal lifespan. Studies have since shown an increase in lifespan in fish, worms, cows, spiders, mice and monkeys, with recent work indicating that a CR diet also brings better health. The question is will it work with humans, and preliminary findings suggest that yes, it will.

Two studies published in 2006 out of Washington University and Louisiana State University showed that subjects on a CR diet for six years had healthier hearts and experienced reduced signs of ageing.

It would probably be impossible to set up and conduct CR trials given the ethical questions associated with experimenting on human subjects. Happily these trials don't have to be set up by scientists, it turns out there are volunteers willing to submit to a life of hunger.

The Calorie Restriction Society (www.calorierestriction.org) has already signed up for this lifestyle and its members are helping to advance research into CR as a way to prolong life.

Society members, who call themselves CRONies (Calorie Restriction with Optimal Nutrition) have developed their own low calorie-high nutrition diets that keep them going but on severely restricted rations. These people in turn have been studied intensively by Dr Luigi Fontana of Washington University who published interesting findings in the Journal of the American College of Cardiology.

He found that people on CR diets had hearts that appeared more elastic than those of age and gender matched controls. Effectively, their hearts beat more like those of much younger people with better rest periods between beats.

Separately a team from the Pennington Biomedical Research Centre at Louisiana State University published findings in the Journal of the American Medical Association about their study called Calerie, (Comprehensive assessment of the long-term effects of reducing intake of energy).

The study put together several groups of male and female volunteers between 25 and 50 and studied them over a six-month period.

One group were put on a CR diet that dropped calorific intake by 25 per cent. Another group reduced calorific intake by 12.5 per cent, but increased the amount of calories being burned by upping their exercise levels. A third group went onto a standard low-calorie diet of 1,800 to 2,000 calories a day until they had lost 15 per cent of their body weight.

All three groups experienced a weight loss, but something else changed for those on the CR diet. They ended the study with lower fasting insulin levels and lower core body temperatures and also had less oxidative damage to their DNA. This is thought to be a marker of ageing.

The researchers now plan a longer study to gauge the impact of CR over a two-year period. "We know people on calorie restriction will lose weight, but this study isn't a weight loss study. We are hoping to learn more about whether calorie restriction can alter the ageing process," says Dr Fontana.

Unfortunately too heavy an engagement with CR also raises the risk of reduced or halted fertility, as discovered in CR studies with mice. This is also seen in female athletes undergoing heavy training regimes where calories are controlled against a background of tough exercise. Shut down the calories and you shut down the reproductive system, a double-edged sword if ever there was one.

On the other hand, animal experiments are strongly suggestive that eating less over time can lengthen life and bring health improvements. CR diets added nearly two years to a dog's lifespan in one study, while squirrel monkeys enjoyed reduced Alzheimer's symptoms under a 30 per cent calorie restriction. And a rat study showed CR reduced age related muscle degeneration and loss, a common effect seen in human ageing.

Evolutionary biologist Dr John Phelan of the University of California, Los Angeles, took a lot of steam out of the debate, however, after developing a mathematical model of human longevity gains under CR.

His model indicated that the promise of living to 125 and beyond under CR was an exaggeration. While starving mice might see a 30 to 50 per cent increase in lifespan or more, humans could only expect an improvement of between 3 and 7 per cent, according to his calculations. This amounts to only a few years, certainly not enough to make the suffering associated with CR worth the bother, he suggested.

"Do you want to spend decades severely limiting what you eat to live a few more years? You will be unhappy and then your life will end shortly after mine ends," he said. "Our message is that suffering years of misery to remain super-skinny is not going to have a big payoff in terms of a longer life."

So if CR isn't going to deliver, will tinkering with telomeres work?

Telomeres are stretches of repeating DNA found at the end of chromosomes that play an essential role in protecting the accuracy of DNA replication during cell division.

Unfortunately each time the cell is copied the telomeres get shorter, until they are so short that they can't protect the chromosome and genetic errors occur to cause age related disease.

This raises the simple question: can we stop the telomere getting shorter and live forever? Maybe Methuselah, who lived to be 936 years according to Genesis 5:27, learned this secret or perhaps it was Adam, who got to a decent 930 years, or so it is claimed in Genesis 5:5.

The Methuselah Foundation (www.methuselahfoundation.org) is funding research in this and any other area that promises to extend life. Telomere studies and research into what repairs it - telomerase - are high on its to-do list.

Dr Richard Cawthon of the University of Utah has already shown in his studies that short telomeres mean a short life.

He found that short telomeres made you three times more likely to die from heart disease and eight times more likely to succumb to infectious diseases in a study of a group of people over 60.

He is amongst those who believe that if you could block telomere loss and counter damage caused by free oxygen radicals and glycation, the improper bonding of sugars to DNA and essential proteins, then perhaps we could live to 1,000 years or more.

The goal would be to find ways to use telomerase as a way to replace the bits lost off the telomeres and so keep them from getting shorter.

Success in this quarter would take one back, however, to the initial questions about the social implications of a life too long. There are huge social implications if the age ratio were to shift too far towards the elderly.

Longer life raises implications for pension schemes, for the determination of retirement age and for the provision of healthcare and nursing home accommodation.

Legal issues pepper these arguments and then there is the issue of where all the extra people are to live. More homes will be needed for the surviving grandparents, great grandparents and perhaps great great grandparents.

This will also have an impact on the availability of resources of all kinds, from food and energy to water and building materials. Will the planet be able to support all of the extra people about the place if we manage to extend lifespan?

If we could push age at death to about 100, then population would rocket to more than 10 billion by 2030, according to calculations by Prof Shripad Tuljapurkar of Stanford University.

"One thing that happens right away, which nobody seems to have thought of, is that the total global population increases dramatically," he says. "In many countries this would have an enormous and not necessarily positive impact."

The US "national dependency ratio" would go from a current one retired person to every five people in the work force closer to four retired people to every five people working. This change would happen in less than 30 years, assuming age at death pushed past its current 80 or so and up to a century.

Tuljapurkar also raises the question: who would have access to the age-lengthening technology? The West has not excelled itself in sharing technology with developing countries and he questions whether poorer countries would also benefit. "Are some people going to be left behind," he asks. "Are we going to make society far more unequal than it is now?"

These are just a few of the implications arising from efforts to extend our time on the planet. And they would rapidly get worse if we achieved the currently impossible and pushed life expectancy to 125 or 150.

These questions aren't going to slow, let alone stop, research into the ageing process which has huge potential to improve quality of life. But the ethicists had better catch up quickly so the implications of an ageing population balance can be thrashed out.