NIH funding of US$80m will support further research into exceptional longevity, continuing a long-running study of families whose members live far longer than statistical models predict.
The funding renews support for the Long Life Family Study, an international project tracking multiple generations, including people who have lived to 100 and beyond.
Researchers are seeking genetic clues that may explain how some individuals avoid or delay common diseases of ageing.
Launched in 2004, the study has enrolled more than 5,000 participants from over 530 families in the US and Denmark.
When enrolment began in 2006, the oldest generation averaged 90 years of age, with several surviving beyond 110. Their children are now in their 80s and grandchildren in their 50s and 60s.
The research is based at Washington University School of Medicine in St. Louis and is supported by the National Institute on Aging, part of the National Institutes of Health.
Michael A. Province, the study’s principal investigator and a professor in the department of genetics at WashU Medicine, said: “So much of medical research is focused on genetic problems that cause disease, and importantly so — we have learned a tremendous amount from that strategy.
“But I am also fascinated by the opposite question: are there genetic variants that cause good things to happen in the body?
“Our study suggests that there is a wide variety of genetic ways that these long-lived families could be protected from chronic diseases as they age.”
Over the two decades since the study began, researchers have identified features linked to healthy ageing.
Many long-lived families showed better cardiovascular health than the average population, including healthier blood pressure and lower rates of diabetes.
In the past five years, findings suggested that health advantages were not uniform, pointing to multiple biological routes to healthy ageing.
Some families stood out for cognition or blood pressure, while others showed stronger lung function or grip strength.
Overall, the families tended to have lower rates of diabetes. One analysis identified a genetic variant linked to lower haemoglobin A1c, a measure of average blood sugar levels used to diagnose diabetes.
The data also revealed a paradox. Obesity was as common in long-lived families as in comparison populations, yet these families had around half the expected number of diabetes cases.
The unusually long lifespans also enabled researchers to identify a gene associated with late-onset Alzheimer’s disease.
In a separate finding, they uncovered a genetic variant linked to extreme longevity and lower blood pressure, but also a slightly increased risk of head and neck cancer, highlighting the need for caution when targeting rare genetic variants.
The renewed funding will allow re-analysis of whole genomes using long-read DNA sequencing, which can detect genetic variations missed by earlier methods.
This will expand the study to 7,800 participants. Researchers also plan to enrol more families, particularly those of African ancestry, as participants to date have been largely of European descent.
On the diabetes findings, Province said: “Something is protecting them from diseases associated with obesity, and we’d love to find out what that is.”
He added: “We plan to enrol more families and especially families of African ancestry.
“The larger and more diverse our dataset, the better we will be able to identify inherited genetic variants associated with longevity and then distinguish which are causing the protective effects and which are just inherited and ‘along for the ride,’ so to speak.”