25 genetic variants linked to human longevity
- December 7, 2017
- University of Connecticut
- Researchers have studied 389,166 volunteers who gave DNA samples to the UK Biobank, US Health and Retirement Study and the Wisconsin Longitudinal Study. In addition to confirming the eight genetic variants that had already been linked to longevity, this study found 17 more to expand the list of known variants affecting lifespan to 25 genes, with some sex-specific.
A new large-scale international study expands the number of genetic markers now known to be associated with exceptional longevity.
Researchers at the University of Connecticut, University of Exeter, University of Wisconsin and University of Iowa undertook a genome-wide search for variants influencing how long participants’ parents lived. Their findings indicated genes that could one day be targeted to help prolong human life.
The team studied 389,166 volunteers who took part in the U.K. Biobank, with confirmation in the U.S. Health and Retirement Study and the Wisconsin Longitudinal Study. DNA samples carry the genetics of biological parents, which provide a practical way of studying exceptionally long lifespans.
Eight genetic variants had already been linked to lifespan, mainly variants that are involved in heart disease and dementia. The latest study, published in the journal Aging, has expanded this to 25 genes in all, with some specific to mothers’ or fathers’ lifespan separately.
“We have identified new pathways that contribute to survival, as well as confirming others,” said study author Dr. Luke Pilling of the University of Exeter. “These targets offer potentially modifiable targets to reduce risk of an earlier death and improve health.”
Researchers found a genetic risk score combining the top 10 variants was statistically associated with parents being centenarians.
How long we live is determined by a range of factors including our lifestyle and how well we treat factors including blood pressure and cholesterol from midlife. However, genetics, and how long our parental relatives lived, also play a role.
Genes involved in senescence, the “frozen” state that cells enter into after being damaged, played an important role in longevity. Drugs targeting senescence have already been shown to extend life in laboratory animals.
Genes related to inflammation and auto-immunity related genes were also prominent, opening up the possibility that precision anti-inflammatory treatments may one day be helpful in extending life.
“These findings add to a growing body of knowledge highlighting specific targets and biological pathways useful for the development of interventions designed to help maintain health, function, and independence in later life,” said Dr. George Kuchel, professor of geriatrics at the University of Connecticut School of Medicine and director of the UConn Center on Aging.
The results confirm that many genetic variants combine to influence human lifespan: no single gene variant has been found to be responsible.
Professor David Melzer, of the University of Exeter Medical School, who led the group said: “This study helps open the way to novel treatment, but the strong role for genes affecting heart disease risk again underlines the importance of controlling blood pressure and cholesterol levels throughout the lifespan. Of course, adopting healthy lifestyles is important, and can probably overcome the negative effects of most of the genes found so far.”
The study was funded by the Medical Research Council.
Other study co-authors include Chia-Ling Kuo, Department of Community Medicine and Health Care, UConn Health; Kamil Sicinski, Center for Demography of Health and Aging, University of Wisconsin; Jone Tamosauskaite, Epidemiology and Public Health Group, University of Exeter; Lorna W. Harries, Institute of Biomedical and Clinical Sciences, University of Exeter; Pamela Herd, La Follette School of Public Affairs and the Department of Sociology, University of Wisconsin; Robert Wallace, College of Public Health, University of Iowa; and Luigi Ferrucci, National Institute on Aging.
- Luke C. Pilling, Chia-Ling Kuo, Kamil Sicinski, Jone Tamosauskaite, George A. Kuchel, Lorna W. Harries, Pamela Herd, Robert Wallace, Luigi Ferrucci, David Melzer. Human longevity: 25 genetic loci associated in 389,166 UK biobank participants. Aging, 2017 [link]