The National Institute on Aging’s Long Life Family Study (LLFS) selected PacBio technology to generate genomic and epigenomic data from as many as 7,800 participants. The effort will rely on PacBio’s Revio systems to capture HiFi long-read sequencing data designed to shed light on why longevity runs in families and what drives healthier aging.
“Long-read HiFi sequencing gives us the accuracy and resolution to see variants and methylation patterns missed by other technologies,” said Michael Province, PhD, professor at Washington University School of Medicine in St. Louis and principal investigator of the project. “By generating comprehensive genomes and epigenomes from extended pedigrees with multiple family members living to exceptional ages in LLFS, we expect to sharpen our ability to pinpoint pathways that influence healthy aging and exceptional longevity.”
The Long Life Family Study is a longitudinal multicenter study focused on identifying a range of factors that contribute to healthy aging and survival. This collaboration marks a next-generation upgrade to LLFS’s existing genomic resources.
To date, the study has enrolled 5,438 individuals across 539 three-generational pedigrees in the U.S. and Denmark and conducted three major rounds of in-home phenotypic visits spanning a period of nearly 20 years. PacBio’s HiFi long-read technology reportedly delivers reads exceeding 15kb, enabling detection of structural variants, repeat expansions, insertions, and phased haplotypes often missed by short reads.
Its methylation-aware protocols also permit direct profiling of 5-methylcytosine signatures in native DNA, according to a company spokesperson, who adds that by applying this approach across thousands of deeply phenotyped LLFS samples, the project aims to:
- Identify rare structural variants segregating with longevity phenotypes
- Link methylation differences to gene regulation, aging trajectories, or disease resistance
- Integrate findings with phenotypic and clinical data to generate new hypotheses for healthy aging
“LLFS is one of the most ambitious aging studies ever undertaken, and one of the first to apply long-read and epigenome sequencing at scale,” said David Miller, vice president of global marketing at PacBio. “We’re proud to support this research with our Revio system, delivering the throughput, cost efficiency, and quality needed to make it possible to develop robust genomic insights.”
Further understanding of the genetic and epigenetic foundations of exceptional longevity may open doors to precision geroscience, anti-aging therapeutics, and new biomarkers of resilience. The LLFS project was recently renewed by the National Institute on Aging for $80 million dollars over five years to perform this sequencing effort as well as recruit new families.
PacBio and LLFS expect to begin sequencing in Q4 2025 at the McDonnell Genome Institute at WashU Medicine, with an initial tranche of ~5,500 samples, and the full ~7,800- sample program spanning five years.
For more information view the Long Life Family Study.
