National Institute on Aging (NIA) Long Life Family Study (LLFS)

The Long Life Family Study (LLFS) is an international collaborative study of the genetics and familial components of exceptional survival, longevity, and healthy aging. Families were recruited through elderly probands (generally in their 90s) who self-reported on the survival history of their parents and siblings, and on the basis of this information, families which showed clustering of exceptional survival were recruited. [Specifically, a Family Longevity Selection Score (FLOSS) ≥7 was required. The FLOSS measures the average excess Observed lifespan over that Expected based upon lifetables, while adding a bonus term for still-living individuals. Thus FLOSS is a useful tool for scoring and selecting families for inclusion in a research study of exceptional survival (Sebastiani et al., 2009, PMID: 19910380)]. Probands resided in the catchment areas of four Field Centers (Boston University, Columbia University, University of Pittsburgh, and University of Southern Denmark). Recruited family members were phenotyped through extensive in-home visits by teams of technicians who traveled all over the USA and Denmark. Blood assays were centrally processed at a Laboratory Core (University of Minnesota) and protocols were standardized, monitored and coordinated through a Data Management Coordinating Center (Washington University). We examined and extensively phenotyped in all major domains of healthy aging, 4,953 individuals in 539 families through comprehensive in-home visits. Of these, 4,815 gave dbGaP sharing permission and had sufficient quantity/quality of DNA for GWAS genotyping. This large collection of families, selected on the basis of clustering for exceptional survival, is a unique resource for the study of human longevity and healthy aging. We estimate that less than 1% of the Framingham Heart Study (FHS) families (a roughly random population family sample) would meet the minimal entrance criteria for exceptional survival required in the LLFS (Sebastiani et al., 2009, PMID: 19910380). Thus, the least exceptional LLFS families show more clustering for exceptional longevity than 99% of the FHS families. Although the LLFS pedigrees were selected on the basis of longevity per se in the upper generation (and the generation above that), the children's generation have significantly lower rates of many major diseases and have better healthy aging profiles for many disease phenotypes (Newman et al., 2011, PMID: 21258136).

The participants had their first in-person visit between 2006 and 2009. After that visit, they were contacted annually by telephone to update vital status, medical history, and general health. Between 2014 and 2017, willing participants completed a second in-person visit. The second visit followed the same protocols and centralized training as the first visit. During the second visit, a portable carotid ultrasound exam was added. Again, participants were continuously contacted annually for telephone follow-up during the period of the second in-person visit and after that. Annual telephone follow-ups currently ongoing, and plans for a third in-person visit are in progress.

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Family
  • Longitudinal
• dbGaP estimated ancestry using GRAF-pop
• Subject Sample Telemetry Report (SSTR)

Families must have Family Longevity Selection Scores (FLOSS)≥7, as defined in Sebastiani et al., 2009 (PMID: 19910380).

Families consist of at least a sibling pair in the upper generation, plus the entire second generation (including children of deceased), and the children's spouses.

Minimum family size is 3, with at least a pair in the upper generation and one child.

Visit 1: In-person exam was between 2006 and 2009.
GWAS was performed after completion of Visit 1.
Visit 2: In-person exam was between 2014-2017.
Annual telephone follow-up has been occurring since participant enrollment in 2006.

• Primary Phenotype: Longevity
• Aging
• Cardiovascular Diseases
• Neoplasms
• Stroke
• Inflammation
• Immune System
• Diabetes Mellitus
• Hypertension
• Dyslipidemias
• Lipids
• Osteoporosis
• Pulmonary Function Tests
• Kidney Function Tests
• Alzheimer Disease
• Depression
• Personality
• Executive Function
• Reproductive History

• BioProject
• MeSH
• PMC

• Principal Investigator Data Management Coordinating Center (Chair, Steering Committee)
  • Michael A. Province, PhD. Washington University School of Medicine, St. Louis, MO, USA.
• Principal Investigators Field Center
  • Thomas Perls, MD, MPH. Boston University School of Medicine, Boston, MA, USA.
  • Anne B. Newman, MD, MPH. University of Pittsburgh, Pittsburgh, PA, USA.
  • Joseph M. Zmuda, PhD. University of Pittsburgh, Pittsburgh, PA, USA.
  • Stephanie Cosentino, PhD. Columbia University, New York, NY, USA.
  • Joseph H. Lee, DrPh. Columbia University, New York, NY, USA.
  • Kaare Christensen, MD, PhD, DMsc. University of Southern Denmark, Odense, Denmark.
• Principal Investigators Central Blood Laboratory
  • Bharat Thyagarajan, MD, PhD, MPH. University of Minnesota, Minneapolis, MN, USA.
• Co-Investigators
  • Mary Wojczynski, PhD. Washington University School of Medicine, St. Louis, MO, USA.
  • Anatoliy Yashin, PhD. Duke University, Durham, NC, USA.
• Funding Source
  • National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA.
• Funding Sources for Genotyping
  • HHSN268201100011I. National Institutes of Health, Bethesda, MD, USA.
  • HHSN268200782096C. National Institutes of Health, Bethesda, MD, USA.