People who reach a very old age may have their genes to thank. Genetic variants that help to prevent DNA mutations and repair any that do occur have been found in supercentenarians and semi-supercentenarians – people who reach the ages of 110 and 105, respectively.
“DNA repair mechanisms are extremely efficient in these people,” says Claudio Franceschi at the University of Bologna in Italy. “It is one of the most important basic mechanisms for extending lifespan.”
Damage to DNA happens throughout our lives. It has many causes, including sunlight and natural radiation, as well as harmful compounds called free radicals generated by normal cell metabolism.
Centenarians’ genes have long been studied by researchers of healthy ageing, but the work by Franceschi’s team is the first to sequence all the genes, or the whole genome, of such a large group of people. The researchers sequenced the DNA of five supercentenarians and 76 semi-supercentenarians from Italy, comparing them with 36 younger people from the same region, who had an average age of 68.
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The team found five genetic variants were more common in the older age groups, which changed the expression of three genes. These variants were also more common in a group of 333 centenarians whose genes had been analysed in a previous study.
Previous work suggests the variants should collectively reduce the number of mutations accumulating in cells by combating free radicals, coordinating the cell’s response to DNA damage and encouraging damaged cells to die. Franceschi’s team found that the semi-supercentenarians did indeed have fewer mutations in six out of seven of the key genes analysed.
If DNA damage goes unrepaired, cells can turn cancerous and can also contribute to other conditions that shorten lifespan, such as heart disease and brain conditions such as Alzheimer’s disease, says Mette Sørensen at the University of Southern Denmark. “The findings are very much in line with the classic way to think about ageing-related diseases.”
Journal reference: eLife, DOI: 10.7554/eLife.57849