NHLBI and NIA The New England Centenarian Study (NECS)

Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age one hundred and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity associated variants that may counter the effects of disease predisposing variants and extend lifespan. The continued analysis of the genomes of these rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme ageing.]]>
Two supercentenarians (a male and a female ages >114) enrolled in the NECS were selected for whole genome sequencing because of their exceptional life and health-spans.]]>
The New England Centenarian Study (NECS) began in 1994 as a population-based study of all centenarians living within eight towns in the Boston area. In 2000 enrollment was expanded to include centenarians from throughout the United States (www.bumc.bu.edu/centenarian). Potential participants were identified from state voter registries, responses to nursing home and senior center mailings, news items appearing in print and on the World Wide Web, and enrollment inquiries made directly to the NECS. The only exclusion criterion for the NECS has been the inability to validate age. Age validation is based on birth certificate, when available, U.S. census data and family history reconstruction. As it became apparent to several studies (the NECS, the Japanese Centenarian Study and the University of Southern Denmark) that the power to discover genetic variants associated with exceptional longevity increased with older and older ages of centenarians, in approximately 2008, the NECS began to emphasize subjects age 105+ years in its recruitment efforts. As of August, 2012, the NECS has >400 subjects age 105-109 years and ~120 subjects age 110+ years in its sample. All subjects are enrolled in studies approved and overseen by the Boston University Medical Campus Institutional Review Board.]]>