X-Message-Number: 20973
Date: Mon, 27 Jan 2003 00:47:00 +1100
From: Philip Rhoades <>
Subject: Centenarians provide genetic clue to age-related disease

 From BioMedNet:

- 24 January 2003

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Centenarians provide genetic clue to age-related disease
23 January 2003 17:00 GMT

by Sabine Lou t

Studies on people who have passed their hundredth birthday are 
revealing the role that genetics plays in age- related disease. Many 
age-related diseases result from inflammatory processes, and 
centenarians enjoy unusually low inflammatory profiles, says Italian 
immunologist, Claudio Franceschi. 
Franceschi, professor of immunology at the University of Bologna, 
Italy, says that his work on centenarians has revealed a genetic link 
between a mechanism for chronic inflammation and aging. "People are 
prone to develop inflammation on a genetic basis," he said.

Franceschi discovered that centenarians present low levels of the 
pro-inflammatory cytokine interleukin 6 (IL-6) and high levels of the 
anti-inflammatory cytokine IL-10. High levels of IL-6, which is 
produced in muscles and bones, is related to loss of muscle mass and 
power with age. Such status translates into frailty and disability and 
the occurrence of diseases such as osteoporosis.

"There is a balance between pro- and anti-inflammatory compounds [that 
is] genetically controlled," Franceschi told delegates at last month's 
Biochemical Society meeting held at Imperial College in London. People 
with certain genes that trigger an imbalance between a pro- and an 
anti-inflammatory cytokine are more likely to suffer from chronic 
inflammation related to ageing, he says.

Although 25% to 30% of longevity is due to a genetic background, says 
Efstathios Gonos, director of research specialised in ageing at the 
National Hellenic Research Foundation in Athens, "It is extremely 
unlikely that there is a single gene causing longevity."

The genetic make up of centenarians can thus provide a useful tool in 
the investigation of age-related diseases. Indeed, Franceschi brands 
centenarians "extreme phenotypes" that comprise all the genetic 
elements necessary to avoid age-related diseases. Conversely, high IL-6 
levels can be considered as a genetic marker for morbidity and 
mortality in the elderly.

This does not come as a surprise to researcher of age-related diseases 
Jonathan Powell, from Unilever Research in the UK. Pro- inflammatory 
cytokine IL-6 is not only linked to the immune system. It is also a 
major metabolic regulator found in primitive organisms such as 
tubeworms and starfish, which have no immune system. "IL-6 has acquired 
some other functionality as we have evolved. But those old metabolic 
functions are still there in us," said Powell.

"As more and more and more of these associations are found, we'll have 
a better idea of the predictive value of those genotypes," he said. 
Genetic markers could then, one day, help in identifying subjects at 
higher risk, and of a new preventative medicine. "Inflammation does not 
describe all of ageing but it has a significant component, " said 
Powell.

"Major age-related diseases all share an inflammatory pathogenesis," 
said Franceschi. Different diseases such as arthritis and Alzheimer's 
disease share the same inflammatory mechanism, he adds. People treated 
with anti-inflammatory compounds for arthritis have a lower risk of 
getting Alzheimer's.

The finding of a genetic susceptibility to age-related disease also 
fits with an evolutionary perspective. Centenarians present low levels 
of pro-inflammatory cytokine IL-6, which protects them from age-related 
inflammatory diseases. According to Franceschi, showing a strong 
inflammatory response is an advantage before the age of 50 but it is 
detrimental in later life when the reproduction-driven force of 
evolution decreases. "From an evolutionary perspective, the objective 
is not to live long but to be fit enough to reproduce", agreed Gonos.

In addition, Franceschi has identified a difference in cytokine levels 
between men and women. He believes that genetics plays a greater role 
in protecting men from inflammatory disease than protecting women, 
because women have more protective hormones. "Women are less prone to 
having high inflammatory status because it is detrimental for bearing 
children," he said.

-- 
Philip Rhoades

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