Found: genes that let you live to 100

This study of Dutch nonagenarians supports the conclusions of the study of NYC Jewish centenarians that I referred to on 15th

SCIENTISTS have discovered the “Methuselah” genes whose lucky carriers have a much improved chance of living to 100 even if they indulge in an unhealthy lifestyle.

The genes appear to protect people against the effects of smoking and bad diet and can also delay the onset of age-related illnesses such as cancer and heart disease by up to three decades.

No single gene is a guaranteed fountain of youth. Instead, the secret of longevity probably lies in having the right “suite” of genes, according to new studies of centenarians and their families. Such combinations are extremely rare — only one person in 10,000 reaches the age of 100.

The genes found so far each appear to give a little extra protection against the diseases of old age. Centenarians appear to have a high chance of having several such genes embedded in their DNA.

“Long-lived people do not have fewer disease genes or ageing genes,” said Eline Slagboom of Leiden University, who is leading a study into 3,500 Dutch nonagenarians. “Instead they have other genes that stop those disease genes from being switched on. Longevity is strongly genetic and inherited.” [Food freaks eat your heart out]

Slagboom and her colleagues recently published studies showing how the physiology of people in long-lived families differs from normal people. Other studies, showing the genetic causes of those differences, are due for publication soon.

“People who live to a great age metabolise fats and glucose differently, their skin ages more slowly and they have lower prevalence of heart disease, diabetes and hypertension,” she said.

“These factors are all under strong genetic control, so we see the same features in the children of very old people.”

The so-called Methuselah genes — named after the biblical patriarch who lived to 969 — are thought to include ADIPOQ, which is found in about 10% of young people but in nearly 30% of people living past 100. The CETP gene and the ApoC3 gene are found in 10% of young people, but in about 20% of centenarians.

The studies show that tiny mutations in the make-up of particular genes can sharply increase a person’s lifespan. Nonetheless, environmental factors such as the decline in infectious diseases are an important factor in the steady rise in the number of centenarians. The human genome contains about 28,000 genes, but they are controlled by a tiny number of so-called regulator genes.

Dr David Gems, a longevity researcher at University College London, believes that treatments to slow ageing will become widespread.

“If we know which genes control longevity then we can find out what proteins they make and then target them with drugs. That makes it possible to slow down ageing. We need to reclassify it as a disease rather than as a benign, natural process,” he said.

“Much of the pain and suffering in the world are caused by ageing. If we can find a way to reduce that, then we are morally obliged to take it.”

An anti-ageing drug which might be taken by millions of people, perhaps from middle age onwards, could be the ultimate blockbuster for the pharmaceutical industry.

Michelle Mitchell of Age UK said: “Ageing is a natural part of life. The key is to ensure that we do not simply extend life but extend the years of healthy life so that people can enjoy, not endure, their later years.”

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Less invasive approaches to IVF may be better for older women

Coming from a large, Irish family with five siblings Dr Marina Murphy, a research chemist, had never expected fertility problems, despite her age. "My husband Rory and I started trying for a family when I turned 36, but two years later, much to our disappointment, nothing had happened."

A visit to her GP in Streatham, south London, followed by blood tests and an examination, revealed that Marina's ovaries and eggs had aged prematurely.

"I was told I had fewer eggs than expected for a woman of my age and warned the quality could be poor," says Marina. "My fertility was more like that of a woman of 40, and my chances of conceiving naturally were around 10 per cent.

"We always assumed we would have our own family, so it came as shock," she says. "But we knew we wanted to try for a child, in whichever way we could."

The couple were told that IVF offered the best chances of a successful pregnancy, and Marina joined the ranks of more than 36,000 women who undertake IVF each year in Britain. Like many of these women, Marina had to undertake the treatment privately. For while the NHS offers infertile couples aged between 23 and 39 three cycles of IVF, standards of service vary across the country, with many primary care trusts offering fewer cycles.

Success rates are low – 19.2 per cent for women aged 38 to 39, dropping to 11.9 per cent for women aged 40 to 42. This, together with the physical and emotional side effects of the large doses of drugs used in the procedure, makes it an arduous and often devastating experience for couples. Many give up after two or three unsuccessful cycles.

Marina had concerns. "As a chemist, I didn't want to throw myself into IVF. I was concerned about the drugs involved." She decided to explore her options
and contacted dozens of fertility clinics before coming across one that offered alternatives to conventional IVF.

Create Health Clinics in London offered two procedures that sounded promising: "soft" IVF, which uses minimal doses of drugs and "natural-cycle" IVF, in which no drugs at all are used. Compared to the average £5,000 cost of a cycle of standard IVF, soft IVF (£2,500 per cycle) and natural-cycle IVF (£1,500) were also considerably cheaper.

"Soft IVF is far less disruptive to a woman's body than the standard approach,"says Dr Geeta Nargund, consultant gynaecologist and director of Create Health Clinics. "With soft IVF, ovary-stimulating hormones are given to a woman during her natural cycle, whereas the practice with conventional IVF is to induce an artificial menopause and then kick-start an artificial cycle,"

"The drug doses are also far lower – just 30-40 per cent of those used in standard IVF. The aim is to collect around six or seven mature eggs rather than 12 to 14. As a result, there is a greatly reduced risk of ovarian hyperstimulation syndrome, a condition in which the ovaries and abdomen can swell and fill with fluid. It can lead to discomfort and nausea and, in severe cases, may prove fatal. It affects up to 2 per cent of women undergoing IVF." explains Dr Nargund.

Marina began her first soft IVF treatment in June 2006. "I was given a 10 per cent chance of success and the first two attempts failed," she says. "Each time, the fertilised egg grew into an embryo but when it was placed back in my uterus, it didn't implant in the womb lining."

Dr Nargund recommended that for her third attempt Marina try natural-cycle IVF. This procedure uses sophisticated scanning techniques to monitor blood flow and the growth of an egg within a woman's natural cycle. Just before ovulation, the egg is collected and fertilised in the laboratory. If it grows into a healthy embryo, it is placed in uterus three to five days later.

Marina's procedure was a success. "To our absolute delight, I became pregnant," she says. "My son Radha is now two-and-a-half."

Dr Nargund, who is president of the International Society for Mild Approaches in Assisted Reproduction (ISMAAR), which aims to promote safer and lower cost assisted reproduction techniques, believes that soft and natural-cycle IVF are particularly successful in older women and is campaigning for these options to be offered more widely.

There is growing evidence that soft IVF is an effective alternative to standard IVF. Research at the University Medical Centre in Utrecht, Netherlands and the University of New Jersey, in the US, found soft IVF and standard IVF had comparable pregnancy rates. In the Utrecht study, published in the Lancet in 2007, both groups achieved a pregnancy rate of 45 per cent.

"The ovaries of women who are nearing the end of their fertility do not respond well to fertility drugs," explains Dr Nargund. "We also know that stimulating the ovaries with higher drug doses is linked to a negative effect on egg quality. That is not what you want when your egg quality and quantity may already be low."

Indeed, scientists at the University Medical Centre in Utrecht found that using lower drug doses and collecting fewer eggs was equally, if not more, effective in producing healthy embryos. Soft IVF produced 39 per cent of healthy embryos compared to just 28 per cent in women given conventional IVF.

"It is generally thought that the more eggs the better, but what you really want is better quality eggs and embryos," says Dr Esther Baart, embryologist at the University Medical Centre in Utrecht, who carried out the study.

Bill Ledger, Professor of Obstetrics and Gynaecology at the University of Sheffield and head of the Assisted Conception Unit at the Royal Hallamshire Hospital, says that the benefits of soft IVF are so clear, he hopes it will one day replace high-dose approaches.

"At Sheffield, we've been offering soft IVF for a long time," he says. "It's more attractive to patients who are wary of higher dose drugs and we get comparable results. With the standard protocol, the woman suffers at least a two-week menopause with hot flushes, night sweats and no libido. With mild IVF, that just doesn't happen."

So why, considering the obvious advantages, is natural-cycle IVF not more widely available?

Some clinics are reluctant to offer the treatment because it is high maintenance and less profitable. Working with a woman's natural cycle relies on staff being available six or seven days a week. Another factor is that clinics wishing to remain at the top of the Human Fertilisation and Embryology Authority's league tables, do not want to offer natural-cycle IVF which requires more attempts to achieve a pregnancy, thereby achieving lower success rates.

"When you perform IVF, you need six or seven eggs to get a meaningful result,' says Paul Serhall, medical director at the Centre for Reproductive and Genetic Health in London. "But in natural-cycle IVF you get just one egg. A woman has to try it over many more cycles to get pregnant. If you are desperate for a child, that is not what you want."

But even a low success rate can mean a lot to a woman if it is her only chance of having a baby. Jennifer Stringford, a writer from London, turned to natural-cycle IVF after being told by a leading teaching hospital that she would never be able to have her own child.

"I'd just turned 42 when one cycle of conventional IVF was abandoned because I wasn't responding to fertility drugs," she says. Jennifer's consultant ruled out natural-cycle IVF as an option. "I was told it is less successful than conventional IVF, so what chance would I have? My only hope for a child would be through egg donation."

But Jennifer happened to read about natural-cycle IVF. "The consultant told me I had just a 5 per cent chance of a successful pregnancy," she says. "But I got pregnant in August 2009 after four attempts. I thought that was pretty good, for someone who had been told to 'forget it.' "

"As long as a woman has a menstrual cycle and is ovulating, she has a chance of getting pregnant," argues Dr Nargund. "Egg quality declines with a woman's age, so you have to be realistic. But it is vital that she is given the option."

"These approaches are safer for the woman, cheaper, less disruptive and vastly reduce the risk of multiple pregnancy," she says. "It really makes sense to consider them instead of blindly using high doses of fertility drugs."

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