EU funds largest-ever study on 'longevity genes'
In medieval Europe, people looking for longer lives sought out alchemists and their elixirs. Nowadays, advances in medical and genetic sciences hope to provide a better formula to unlocking the secrets of longevity. The Genetics of Healthy Ageing (GEHA) is an EU-funded project, aimed at proving that specific genes exist that are enable individuals to live to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. It is the largest ever study on 'longevity genes'. In recent years, a number of human studies have tried to identify these genetic components which could increase the life-span. But the task is not an easy one, as Professor Claudio Franceschi of the University of Bologna and coordinator of the GEHA project explains. 'Genes associated with longevity don't work in a void. Unlike the laboratory animals which are tested in a controlled environment, humans interact with the environment and have multiple factors affecting them such as lifestyle, nutrition, and culture.' This renders results from genetic studies on humans more 'confused' than those from strictly controlled animal models in which these variables can be minimised. But unpredictable results can paradoxically mean more reliable ones, according to the professor. 'The fact that humans are heterogeneous means these studies do not suffer from the highly 'artificial' conditions to which animals used in studies to assess the determinants of longevity are exposed,' explained the professor. He gave the example of studies on the elderly in which chronic inflammation was observed. 'Such observations were completely overlooked in experiments on mice due to the 'clean' conditions typical of well controlled animal experiments.' Another problem is the lack of comparable data. Although some studies have taken place on longevity genes, they have been population specific. 'We need to collect a very large number of subjects who are enriched with longevity genes from different geographical and ethnic backgrounds,' explained Professor Franceschi. This is where the GEHA project comes in. The project brings together demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians and statisticians from 11 European countries and China. It samples 2,650 sib-pairs (pairs of siblings) over the age 90 years. These will be paired with 2,650 'young' controls aged 60 years in order to carry out a comparative genome analysis. 'We chose 60 because mortality rates start increasing after this age.' The study is unprecedented in terms of its size, and Europe is way ahead in the field according to the professor. There is a plan to start a similar project in Japan and Japanese scientists recently visited the GEHA consortium partners to see how they carry out the study. It is expected that the Japanese group will use the same methodology that the GEHA has designed. In the US, a study has also started on 500 families. The GEHA project started in 2004 and has so far collected nearly half of the samples needed (1,060 trios - one pair and one young subject). 'Originally, we thought that it was possible to collect all the samples for the study by the end of the third year [2007]. But it hasn't been that easy,' said Professor Franceschi. For one thing, finding two siblings over the age of 90 and in good health is very rare. And even when these elusive couples are found, they are hard to hold onto. The project makes use of local registries in each of the 12 participating countries to recruit the pairs. 'Often when we find a couple, one is found to be living aboard or it happens that one dies following recruitment,' explained Professor Franceschi. The project uncovered a refusal rate of about 50 per cent which the professor said was to be expected. The recruitment process is lengthy, due to the frailty of the subjects and the number of steps involved, each of which is supervised by an ethics board. 'It was very important to have the ethical dimension of the project in place from the very beginning. The EU imposes very strict ethical rules on studies of this kind, which is understandable given that the data is very personal and sensitive,' said the professor. When a pair of subjects agree to participate, they undergo cognitive and health tests to determine their health status. If found to be healthy, then a mouth swab or blood is taken and pairs are asked to answer a questionnaire about their living and eating habits. In addition, siblings are paired with 'younger' controls who have the same ethnic, geographical and environmental backgrounds. All recruiting centres send the blood or swab samples back to the National Health Centre in Helsinki for analysis. 'This ensures that the quality of the DNA is consistent.' There is also a centralised functional database for the survey findings,' said Professor Franceschi. According to the professor, the project consortium aims to have finished recruitment and collection of DNA in six months to a year. Then work will focus on three genomic regions, implicated in aging and longevity in previous studies. All recruits will have their mitochondria genotyped for DNA 'haplogroups' (genetic population types) and mutations, known to play a major role in aging and longevity. 'Our hope is to prove that universally shared 'longevity' genes exist between populations,' said professor Franceschi. 'We might also find that some genes are specific to a geographic population. For diseases like schizophrenia, we know that the same genes would be identified in France as in Poland. But genes linked to longevity, which are more complex because they interact with the environment, could differ.' The project will also try to identify gender and ethnic specific 'healthy ageing' genes. The study outcome could have important implications for Europe, where it is estimated that one-third of the population will be over 60 years old by 2050. Finding the genes that protect us from illnesses and keep us healthy in our old age could help to us reduce the costs for health systems, which will increase dramatically as our population ages.