A US$80m grant will support exceptional longevity research into families whose members live far longer than average, as scientists look for genetic clues to healthy ageing.
The funding renews support for the Long Life Family Study, a long-running international project examining multiple generations of families with unusually high numbers of people living to 100 and beyond.
The work is supported by the National Institute on Aging of the National Institutes of Health.
Launched in 2004, the Long Life Family Study builds on Washington University School of Medicine in St. Louis’s work in genetics and genomics, including analysing whole genomes of participants to identify genetic clues linked to longevity.
Over two decades, the study has reported insights into healthy ageing, including that many long-lived families have better cardiovascular health than average, with healthier blood pressures and lower rates of diabetes.
Around the world, populations are ageing, and projections suggest more people will develop chronic conditions such as cardiovascular disease, diabetes and Alzheimer’s disease.
Studies estimate the number of people over 50 with at least one such condition could double by 2050.
The study has enrolled more than 5,000 participants from more than 530 families living across the US and in Denmark.
The oldest generation averaged 90 years of age when enrolment began in 2006, and several survived beyond 110.
Today, the children of that first generation are entering their 80s and the grandchildren are in their 50s and 60s.
The Framingham Heart Study, which has tracked families in Framingham, Massachusetts, since 1948, serves as a comparison group.
Over the past five years, researchers have found the families are not uniform in how they experience unusual health, suggesting multiple routes to healthy ageing.
Some families stood out for cognition or blood pressure, while others had markedly robust lung function or grip strength.
In general, the families tended to have lower rates of diabetes.
One analysis identified a genetic variant associated with lower haemoglobin A1c, a measure of average blood sugar levels used to diagnose diabetes.
According to Michael A. Province, the study’s principal investigator and a professor in the department of genetics at Washington University School of Medicine, obesity is as common among long-lived families as among those in the Framingham Heart Study, yet long-lived families have only about half the expected cases of diabetes.
“Something is protecting them from diseases associated with obesity,” Province said, “and we’d love to find out what that is.”
The unusually long lives of participants also helped researchers identify a novel gene associated with late-onset Alzheimer’s disease.
In an unexpected finding, one genetic variant was associated with both extreme longevity and lower blood pressure but also a slightly increased risk of head and neck cancer, pointing to the need for caution when developing therapies based on rare variants that may carry both positive and negative health effects.
“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,” Province said.
“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.”
A new phase of the study will re-analyse whole genomes for all current and past participants using the latest long-read sequencing technology, which can resolve parts of the genome missed by older methods.
The technology will also be used to analyse new participants’ genomes, bringing the total number of participants to 7,800 individuals.
Because most of the oldest participants have now died, investigators are seeking to enrol new families with very long-lived oldest generations.
They also aim to broaden the genetic backgrounds of participating families, which have been largely of European descent.
“We plan to enrol more families and especially families of African ancestry,” Province said.
“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.
“This is a critical question as we seek possible ways to replicate these protective effects for people without the beneficial genetic variations.”
