Dataset Information

NHLBI and NIA The New England Centenarian Study (NECS)

ABSTRACT:

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.

PROVIDER: phs000451.v1.p1 | EGA |

REPOSITORIES: EGA

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Publications

What does it take to live to 100?

Perls Thomas T Levenson Robin R Regan Meredith M Puca Annibale A

Mechanisms of ageing and development 20020101 2-3

Centenarians disprove the ageist myth "the older you get, the sicker you get"; they live 90-95% of their very long lives in excellent health, only to experience illnesses in the very last few years of their lives. Thus, it appears that in order to live to 100, one must age relatively slowly and markedly delay and/or escape age-associated diseases. How they achieve such a survival advantage is still a mystery though it is becoming increasingly clear that a substantial genetic advantage plays a ro ...[more]

PMID: 11718815

Publication: 1/48

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Project description:<p>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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19910380" target="_blank">19910380</a>)]. 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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19910380" target="_blank">19910380</a>). 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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/21258136" target="_blank">21258136</a>).</p>

Dataset Information

NHLBI and NIA The New England Centenarian Study (NECS)

Publications

What does it take to live to 100?

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