How to live to a ripe old age
without losing your marbles

Mark Henderson, Science Editor

A gene variant that is linked to long life also helps to preserve mental lucidity in old age, scientists have discovered.

An Israeli study involving 158 people who lived to 95 or beyond has found that those who inherit a particular version of the gene CETP are twice as likely to have a sharp and alert brain when they are elderly.

They are also five times less likely than people with a different version of CETP to develop Alzheimer’s disease and other forms of dementia, according to the study by a team at the Albert Einstein College of Medicine at Yeshiva University.

The insights into how ageing affects the brain could lead to ways of protecting cognitive function in old age.

If drugs could be developed which mimic the protective function of the CETP VV variant they could transform the quality of life of the ageing population.

“Without good brain function, living to age 100 is not an attractive proposition,” said Nir Barzilai, director of the college’s Institute for Ageing Research. “We’ve shown that the same gene variant that helps people live to exceptional ages has the added benefit of helping them think clearly.

“It’s possible that CETP VV’s cognitive effect is to protect against Alzheimer’s disease. In studying these centenarians, we hope to learn why they’re able to resist diseases that affect the general population at a much younger age. This knowledge should greatly aid our efforts to prevent or delay the onset of age-related diseases.”

In the study, Dr Barzilai’s team tested people aged 95 or more to see which version of the CETP gene they had.

Ashkenazi Jews, who are of Eastern European origin, are often used as the subjects for genetic research because their restrictive marriage practices mean that their genes vary less than other populations.

CETP is a gene that makes the cholesterol ester protein, which in turn influences the size of the particles in which both “good” (high-density lipoprotein) and “bad” (low-density lipoprotein) cholesterol appear in the blood.

Larger particles are thought to be beneficial because they are less likely to become wedged into the linings of the blood vessels, where they can clog the arteries causing coronary heart disease, stroke and some forms of dementia and cognitive decline. People who have the CETP VV variant have larger cholesterol particles in their blood, and previous research has shown that they are more likely to live longer than people with other versions of the gene.

About 8 per cent of people aged 70 have the CETP variant, but this rises to 25 per cent among centenarians. This is thought to play a key role in explaining why some people live to very old ages — in developed countries, about 1 in 10,000 people lives to 100.

The research, published in the journal Neurology, found that those with CETP VV were twice as likely as the others to have good brain function.

A separate investigation of 124 Ashkenazi Jews aged between 75 and 85 found that CETP VV appeared to protect against dementia: those with the variant were five times less likely to suffer from it.

“It’s possible that this gene variant also protects against the development of Alzheimer’s disease,” Dr Barzilai said.

Little effort has been made to identify the reasons for longevity in exceptionally old people, and why they don’t develop disease.

“Our results bring us a step closer to understanding the role that genes play in longevity.”

It's all in the genuis

Ernst Mayr One of the fathers of modern evolutionary biology, he was still working when he died in February 2005 aged 100. After his official retirement in 1975, he published more than 200 peer-reviewed papers — more than some scientists achieve in an entire career

Lucian Freud At 84, one of Britain’s foremost painters. Recent subjects include the Queen, Harold Pinter, the playwright, and Kate Moss, the model. In November a poll of 500 in the art world named him their favourite contemporary artist

Bob Hope The British-born comedian and entertainer who became an American icon performed for 11 American presidents, and maintained his keen sense of humour until his death in 2003, aged 100. One of his daughters reports that on his death bed, when asked where he wanted to be buried, he replied: “Surprise me”

Leni Riefenstahl The German film director is best known for her films of Hitler’s Nuremberg rally and the 1936 Olympics but had an acclaimed post-war caree. She learnt underwater photography in her old age, and released a film called Underwater Impressions on her 100th birthday in 2002

Queen Elizabeth, the Queen Mother Died in 2002, aged 101. In 2000 she was a sprightly and active participant in celebrations of her 100th birthday. She made public appearances until shortly before her death

Strom Thurmond Elected as Senator for South Carolina in 1954, and did not leave office until 2003, shortly before his death at the age of 100

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