What are the secrets to a long and healthy Life?

Further, the measured phenotypes are highly heritable cross-sectionally and longitudinally; however considerable familial phenotypic heterogeneity is present. To better understand this heterogeneity and the why and how these families are protected we will: conduct a third in-home visit with existing participants; recruit and enroll the grandchildren of the proband generation for their initial visit; combine linkage and association analyses to identify rare and lineage specific variants for cross-sectional and longitudinal HAPs and EL and their interaction with lifestyle exposures; perform comprehensive OMICs on LLFS pedigrees to discover biologic mechanisms leading to the heterogeneous familial patterns of HAPs and EL in LLFS pedigrees, and discover additional causal variants. Finally, we will combine all the data using systems biology and data integration to more comprehensively explain the biology of healthy aging.

The purpose of the LLFS is to study families in the United States and Denmark that are ALL enriched for exceptional longevity (EL). EL is a complex trait that is likely influenced by multiple genes with small effects interacting with lifetime exposures. The knowledge gained from studying these families will be in why and how they are protected and thus living exceptionally healthy long lives.

This project is supported by the National Institutes of Health’s National Institute on Aging, grant U19AG063893.