For some, life begins at 100

While old age brings its own hardships, researchers have found a less bleak vision of the future after one leaves 99 behind.

Ali Mohammed Hussein, a former charcoal burner and farmer in Lebanon, is believed to 135 years old, according to official Lebanese records. New research has made scientists believe that genes only staShow more

This year the number of pensioners in the UK exceeded the number of minors for the first time in history. That's remarkable in its own right, but the real "population explosion" has been among the oldest of the old - the centenarians. In fact, this is the fastest-growing demographic in much of the developed world. And their ranks are set to swell even further, thanks to the ageing baby-boomer generation: by 2030 there will be about a million worldwide.

These trends raise social, ethical and economic dilemmas. Are medical advances artificially prolonging life with little regard for the quality of that life? Old age brings an increased risk of chronic disease, disability and dementia, and if growing numbers of elderly people become dependent on state or familial support, society faces skyrocketing costs. This is the dark cloud outside the silver lining of increasing longevity. Yet researchers who study the oldest of the old have made a surprising discovery that presents a less bleak vision of the future than many anticipate.

It is becoming clear that people who break through the 90-plus barrier represent a physical elite, markedly different from the elderly who typically die younger than them. Far from gaining a longer burden of disability, their extra years are often healthy ones. Supercentenarians - people aged 110 or older - are even better examples of ageing gracefully. "As a demographic group, they basically didn't exist in the 1970s or 80s," says Craig Willcox of the Okinawa Centenarian Study in Japan. "They have some sort of genetic booster rocket and they seem to be functioning better for longer periods of time than centenarians."

The average supercentenarian had freely gone about their daily life until the age of 105 or so, some five to 10 years longer even than centenarians, who are themselves the physical equivalent of people eight to 10 years their junior. This is not just good news for the oldest old and for society in general; it also provides clues about how more of us might achieve a long and healthy old age. Gerontologists point to four key factors: diet, exercise, "psycho-spiritual" and social, so anyone aiming for a century should not underestimate the power of lifestyle - despite the odd centenarian who proudly claims to have smoked 60 cigarettes a day for decades. Thomas Perls, who heads the New England Centenarian Study, believes that up to 70 per cent of longevity is from non-genetic factors. Nevertheless, many people who live well into old age do tend to have another advantage: an inherited genetic pass.

Take a close relative of a centenarian and you can put good money on their chances of living a long life. Among Americans born in 1900, brothers of centenarians were 17 times as likely to reach a century as their peers, and sisters, eight times. The New England study reveals that the children of centenarians are less than one-third as likely to die of cancer as the general population, and less than one-sixth as likely to die of heart disease.

Further evidence of a genetic link comes from longevity hot spots. Okinawa in Japan is the front runner. At 58 centenarians per 100,000 people (and rising), it has the world's highest proportion in this age group - more than five times the level of some developed countries. Like other hot spots, including Sardinia and Iceland, Okinawa is an isolated island community, which leads to higher levels of inbreeding and a clustering of genetic variants. While such genetic similarity usually has detrimental effects, in these hot spots it seems to have united and maintained genetic variants that predispose people to a long life.

Gerontologists have found that the influence of environmental factors such as wealth or education on lifespan fades as we age, while that of genes increases. By comparing 10,000 pairs of Scandinavian twins, Christensen found that genes start exerting a strong influence on our lifespan only after the age of 60. This makes the "centenarian genome" a key resource for identifying "longevity genes", an invaluable step in understanding the physiological processes underlying long lives.

Such genes have been found in abundance in other organisms - including more than 70 in the worm Caenorhabditis elegans. Unfortunately, it's a different story in humans. While many candidate genes have been suggested to affect lifespan, very few have been consistently verified in multiple populations. Until recently, the only exception was ApoE, and in particular a variant of this gene known as e4, which bestows carriers with a much higher than average risk of developing Alzheimer's and heart disease. Across the world, this unfortunate version of ApoE is about half as common in centenarians as in younger adults.

Last year, a second promising candidate emerged - a variant of a gene called FOXO3A. At the University of Hawaii, a team led by Bradley Willcox, Craig's identical twin, found that people who carried two copies of a particular form of the gene were almost three times as likely to make it to 100 than those without the variation, and also tended to start their journey into old age with better health and lower levels of stroke, heart disease and cancer.

"There are so many false positives in this field that FOXO3A is very exciting," says Bradley Willcox. FOXO3A is involved in several signalling pathways that are conserved across animal species. It controls the insulin/IGF-1 pathway, which influences how our bodies process food. It also controls genes that protect cells from highly reactive oxygen radicals - molecules often thought to drive human ageing through the cumulative damage they wreak on DNA.

FOXO3A could even protect against cancer by encouraging apoptosis, whereby compromised cells commit suicide. The variant of FOXO3A associated with longevity is much more prevalent in 100-year-olds even than in 95-year-olds, which clearly demonstrates the value of studying the centenarian genome. So far the search for longevity genes in humans has been extremely difficult, but prospects brighten as genomic technologies become faster and there are more centenarians to study. Only a lucky few win the genetic lottery of longevity, but if we understand what sets them apart, we may be able to make the rest of us more like them by using lifestyle or therapeutic interventions.

Such medical advances will not only extend our lives, but also help us remain healthy and independent for as long as possible. www.newscientist.com