Nappy clue to happy old age

Vittoria D'Alessio meets a medical doctor investigating the power of the womb.

Avan Sayer is on a quest for the elixir of life. Her research will help us understand how one person can live like a saint and die of a heart attack at 40, while another can pass away peacefully after 90 sedentary years of chain-smoking and culinary debauchery.

Her work towards a PhD in clinical epidemiology is helping to uncover the power of the womb in shaping people's health throughout their lives. It may spawn a planet of children so pampered by their expectant mothers that the distresses of ageing may, to them, become a footnote in history.

Sayer's studies are based on the revolutionary research on "foetal programming" by David Barker, director of the Medical Research Council's environmental epidemiology unit at the University of Southampton.

Over the past decade, Professor Barker's postulations have revolutionised traditional understanding of the biological triggers for chronic diseases in old age. Genes and lifestyle take a poor second place in determining who dies of what and when, according to Professor Barker's findings. Far more important, it would seem, is exposure to certain compounds and/or hormone signals during the early stages of development.

Professor Barker's theories were crystallised when he observed that in the north and west of Britain - hot spots for heart attacks - there had been a high death rate among newborn babies in the early years of the century. A high neonatal death rate is a reliable marker of poverty and many of these deaths were at the time attributed to low birth weight.

After exhaustive research which extended to the United States, China, Cuba, Australia and Nigeria, Barker concluded that the small size of newborns was an important predictor of a greatly increased susceptibility to coronary heart disease, stroke, diabetes, high blood pressure and obstructive lung disease.

He suggested that the most likely cause of baby's stunted development is that it received poor nutrition while it was a foetus, during a particularly sensitive period when organs undergo rapid cell division.

When Sayer, now 33, joined Professor Barker's research team four years ago, she became the latest in a long line of medics there. She was recruited for her training in general medicine and her specialisation in geriatric medicine. Sayer set herself the ambitious task of exploring markers of old age that are non-life-threatening and working out whether they too are related to poor early growth.

"This was difficult," she says. "Not much is understood about ageing and first I had to ask, what is ageing? I decided to look at a battery of things including the lens and the retina, hearing, muscle strength, skin thickness and cognitive function."

The MRC had already unearthed an impressive stock of data-dense ledgers in Hertfordshire dating back to the 1930s. "There had been a panic over high death rates in babies at that time, and a system was set up whereby midwives and health visitors supported mothers. The ledgers recorded birth weights, growth rates and how the babies were fed."

She chose a population sample from north Hertfordshire, previously untouched by Professor Barker's research. All subjects were aged between 64 and 74 - an age bracket associated with the first stages of the diseases of ageing. Of the 1,400 citizens approached, 850 agreed to take part in the study.

"It took six months to set up the study, a year to collect all the information and for the last year I have been analysing the data and writing it all up," she says.

Her hard work, as yet unpublished, is yielding astonishing results. After adjusting for the underlying risk factors associated with social class (the assumption being that lower social classes consume more cigarettes and alcohol), Sayer has found a considerable dichotomy in the signs of ageing between people who were bonny babies and their skinnier counterparts.

One particularly arresting finding relates to lens opacity. It was already known that lens opacity early in life indicates that cataracts may develop later in life. Sayer found that one group of elderly people had lenses that were 16 per cent more cloudy than another group - and back in the 1920s the people in this first group had weighed under 18 lbs at one year old while those in the second group had weighed lbs.

The smaller babies also demonstrated the poorest hearing at the onset of old age, with a 26 per cent difference in auditory faculties between the lightest and heaviest babies.

There was also a statistically significant relationship between cognitive function and weight in the first year of life. Small babies also showed a much lower grip strength in their 60s and 70s, irrespective of their heights as adults.

Frail babies also went on to develop more papery skin, according to a non-invasive ultrasound skin-measuring technique. Babies weighing 18 lbs at the age of one year showed a skin thickness of 1.2 mm later in life, and this increased by 0.05 mm in babies that weighed 26 lbs at the same age.

No relationship was found, however, between early growth and tooth decay; changes in the retina; loss of vision, or inter-ocular pressure (the latter is a marker of the eye disease, glaucoma).

Jennifer Evans, the ophthalmic epidemiologist on Sayer's project, says: "The results we had were very exciting, but you are never quite sure how to interpret results like these. Is it a chance finding?" After verifying the results through a further study, she wants to explore what the mechanism could be. "I think nutrition is very important in the formation of cataracts," says Evans. "I'm just not sure when it is important." It could be important just in the womb, or at some point after birth - or at both stages.

In the germinal days of their research, Evans and Sayer were motivated by the same niggling riddle: how was it possible that the odd extra pound at birth could mean so much later on?

Sayer now favours the theory that ageing is related to the body's reduced ability to repair itself after wear and tear.

"My theory is that the rate of repair is less good in those who did not grow properly - in these individuals the enzymes of repair are less effective. DNA repair may also be critical to ageing. I would like to look at DNA segments of people who have aged well and badly and compare this data with good and bad growth as babies."

Sayer is one of a disappearing breed of medics who, inspired by a year of research in the middle of their medical degrees, decide to head into science rather than practical doctoring. Sayer took time out in the middle of her medical degree to do a BSc in pharmacology.

"I enjoyed my BSc so much that I knew that at some point in my medical training I would want to do some research, and I knew a little bit about epidemiology and that I enjoyed a more statistical approach to medicine. So when the time was right I picked out the centres of excellence and wrote around. I met David Barker and was really impressed. The unit here seemed so dynamic and the training quite unusual. Normally, epidemiological training takes the route of public health, but Dr Barker is a hospital doctor and does his work in the context of clinical medicine."

Barker recruited Sayer and sponsored her for a Pounds 175,000 Wellcome training fellowship in clinical epidemiology. This fellowship has given her four years in which to complete both an MSc at the London School of Hygiene and Tropical Medicine and her PhD.

With reams of north Hertfordshire data screaming out for analysis, it is a wonder that Sayer can contemplate a tomorrow beyond her computer's sophisticated statistics programme. Yet despite the workload - and two pre-school children - she has mapped out the details of her post-thesis career.

"I will go back to being a senior registrar in geriatric medicine to complete my medical training and eventually I will aim for an academic geriatric department, combining work with research," she says.

And if she can make space in this action-packed future for part two of her work in north Hertfordshire, all the better. "I want to go back to these people and follow up with some studies in molecular biology."