It is a mystery older than Methuselah: why are we born to die after our allotted three-score years and ten?

Now scientists have discovered how genetic damage to cells and our ability to carry out repairs are the major factors in determining how long we will live.

The research could lead to new treatments for horrific diseases which cause young children to age prematurely and die, with trials expected within a year.

And while Methuselah’s 969 years and an elixir of eternal life are still in the realms of religious belief and science fiction, researchers believe it is now theoretically possible at least to extend lifespan “significantly”.

It was once thought the ageing process was pre-programmed, hardwired into the human condition, and that death was simply a fact of life. But life expectancies in developed countries have stubbornly continued their upwards rise, by about two years every decade or about five hours a day.

A paper made public yesterday by the journal Nature detailed a study of mice which grew old and died within three weeks because they lacked genes involved in repairing damage to DNA, and also the discovery of a new disease which results in premature ageing. Professor Laura Niedernhofer, of Pittsburgh University, said their findings showed that DNA damage and the ability to repair it were crucial in determining lifespan.

“Damage, including DNA damage, drives the functional decline we all experience as we age,” she said. “But how we respond to that damage is determined genetically, in particular by genes that regulate growth hormone and insulin.

“Avoiding or reducing DNA damage caused by sources such as sunlight and cigarette smoke, as well as by our own metabolism, also could delay ageing.”

A key finding was that the mice which lacked genes to repair DNA damage and died in three weeks went through similar changes to mice which lived the normal two and a half years, showing that the genes were involved in the natural ageing process.

Professor Jan Hoeijmakers, the head of genetics at Erasmus University Medical Centre in Rotterdam, Netherlands, and a co-author of the report, said it was “early days”, but understanding why we get old was paving the way for new treatments for age-related diseases.

“We may go to these diseases with children that are rapidly ageing to see if we can help these patients. Maybe in six months to a year, he said.”

In the longer term, it could lead to a healthier old age and a longer life, perhaps more likely to be ended by disease or injury than old age, but not immortality.

“It is not valid to say this is the secret of eternal life; that would be irresponsible,” Prof Hoeijmakers said.

“I think it’s impossible to make repair perfect; nothing is perfect in nature. There will always be some damage that persists and causes cell death that contributes to ageing. I think indeed theoretically it should be possible to extend lifespan significantly – if we had all the knowledge – but we are very far from that.”

The simple act of being alive causes damage that leads to death. A by-product of breathing is reactive oxygen, which causes damage to DNA that must be continually fixed. As the body ages, the damage builds up and the metabolism changes to focus on repair work.

“There may be ways in which we can trigger this survival response – which promotes healthy ageing, tries to prolong your lifespan – using drugs or chemicals,” Prof Hoeijmakers said.

A spokesman for the Roman Catholic Church said that the research sounded “fascinating”, with the potential for new treatments for diseases that cause premature ageing.

“As for the implications of lengthening lifespans, these are far more social than theological,” he said. “Clearly, life will still come to an end. We may have to wait a bit longer to meet our maker, but it sounds like sooner or later we all will.”

LINK TO DNA
THE researchers began studying the link between DNA damage and ageing in the late 1990s, when a German doctor treating a 15-year-old Afghan boy contacted the Erasmus medical centre for help.

His patient suffered from hearing loss, sight problems, muscle wasting and weight loss, anaemia, hypertension and kidney failure.

The researchers tested cells for one form of DNA repair mechanism and found almost no activity at all. They then analysed his DNA and discovered he had a mutation on a gene which played an important part in the repair process and that this had led him to age prematurely.

Other forms of ‘progeria’ include Cockayne’s syndrome, which restricts growth and causes premature ageing and death.