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. DNA samples carry the genetics of biological parents, which provide a practical way of studying exceptionally long lifespans.

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. Their findings indicated genes that could one day be targeted to help prolong human life.

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 in the U.K., 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.”

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.

This work was funded by the Medical Research Council (MR/M023095/1) in the U.K.; the Intramural Research Program of the National Institute on Aging, U.S. National Institutes of Health; and UConn Health.

The Health and Retirement Study is a longitudinal project sponsored by the National Institute on Aging (NIA U01AG009740) and the Social Security Administration. This research uses data from the Wisconsin Longitudinal Study (WLS) of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (AG09775, AG21079, and AG33285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation, and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the WLS is available at http://www.ssc.wisc.edu/wlsresearch/data. This material is the result of work supported with resources at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.