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Five new genetic regions linked to long life in humans

21 December 2015

By Dr Ashley Cartwright

Appeared in BioNews 833

Scientists have identified five genetic loci associated with extreme longevity.

The 'informed genome-wide association study' assessed existing genomic data on 14 diseases and used that information to narrow the search and seek out gene variants that had an overlapping association with longevity.

The researchers used two existing studies of human longevity: the New England Centenarian Study, which included 801 centenarians and the 90PLUS study, which included 5406 elderly individuals over the age of 90. The researchers then replicated their findings with data from three additional centenarian cohorts from Southern Italy, Northern Italy and a pool of Ashkenazi Jews.

The research findings, published in PLoS Genetics, identified five longevity loci that provide clues about mechanisms for healthy ageing. One of these loci was the previously identified APOE locus, known to be involved in Alzheimer's disease. The other four loci are novel and include the CDKN2B/ANRIL gene locus, linked with cell senescence; ABO, linked with blood group; SH2B3/ATXN2, associated with cell signalling; and the HLA gene, linked to autoimmunity.

Each of these genetic loci was found to have a variant that can reduce ('bad' variants) or increase ('good' variants) a person's chances of reaching 100. The variants identified were common in the control populations studied, but in the ageing cohorts, centenarians seemed to have fewer 'bad' variants.

Previous research using twin studies suggests that genetics plays a considerable role in lifespan. Furthermore, it is common for siblings from the same family to live long lives.

'Those sorts of things argue persuasively that about 20 percent of lifespan is genetic, possibly more for living to be extremely old,' lead author Professor Stuart Kim from Stanford University told New Scientist.

Most attempts to look for genes related to ageing have compared the genomes of centenarians and people with average lifespans to pick out the regions where they differ. However, despite a number of studies, only the APOE locus has been identified as a consistent contributor to longevity.

In this study, the researchers took a more targeted approach to take advantage of existing knowledge on the genetics of disease.

Professor Kim said: 'Ageing and disease are closely related, and a great deal is known about the genetic basis of disease risk. It seems intuitively obvious that avoiding disease is part of the strategy of becoming a centenarian.'

He added: But there is a really, really strong dogma in the field that there was no depletion of disease genes in centenarians, and that all of their survival benefit was coming from protection from anti-ageing genes. But I think they were wrong.'

The incidence of disease increases with age, so understanding genetic factors for successful ageing could have a large impact on health.

Commenting on the research findings in the New Scientist, Dr Timothy Cash from the Spanish National Cancer Research Centre in Madrid said: 'It's the first time someone has shown that particular disease [variants] are depleted in centenarian populations. It points to important processes that are impaired in ageing populations.'

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