Research thus far indicates that exceptional longevity (EL) and specific exceptional survival (ES) phenotypes are familial and suggests that a significant component of that familiality is genetic. Once thought to be much too complex a puzzle of environmental, behavioral, genetic and stochastic factors, EL and likely associated ES phenotypes appear to be likely associated with a number of discernable and influential factors. The sampling frame for this proposed Exceptional Survival in Families Study Center will be a population-based sample of individuals achieving EL, defined as males age >= 98 years and females age >100 years, living in Massachusetts and Connecticut. These LLIs represent the 1% oldest members of the cohort born around the turn of the 20th century. Based upon our current ability to enroll 700 age-validated subjects per year, the provision of additional resources and our experience with a previous smaller population-based study, we will enroll 809 LLIs, 806 siblings and 692 offspring of LLIs during the 3 year recruitment period of this 5 year project. Since this is a population-based study, we will be able to estimate for this region, the yield of LLIs, sibships and offspring as well as survivorship according to specific traits. Medicare and Minimum Data Set (MDS) data will be provided by the Centers for Medicare and Medicaid Services to help gauge sensitivity of the census lists and representativeness of the enrolled set, to investigate regional and nationwide Medicare utilization and MDS data among LLIs in order to generate candidate ES phenotypes and to augment phenotypic data on enrolled subjects. We have observed that siblings of centenarians experience half the mortality of their birth cohort from age 20 up through extreme old age. Work by EIo, Kestenbaum and colleagues supports the hypothesis that there are important childhood related events that play significant roles in the ability to achieve EL. A portion of this proposed effort will be dedicated to further investigating such factors. At older ages, a relative survival advantage could be typified by specific ES phenotypes which we shall investigate concurrently among offspring of LLIs and retrospectively or concurrently, depending upon the phenotype, among LLIs. Family-based analytic approaches will be used to investigate EL and ES phenotypes for familial aggregation and modes of transmission. By enrolling LLIs and their family members in a population-based sample and conducting a phenotyping and analytic effort as an integral component of the MCS-ESF, we will be able to study these rare families in a manner that will facilitate data and future genetic material sharing, testing for reproducibility across sampling frames, and an intellectual effort that will far exceed what any one isolated study could achieve on its own.
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| Bae, Harold; Gurinovich, Anastasia; Malovini, Alberto et al. (2018) Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies. J Gerontol A Biol Sci Med Sci 73:1439-1447 |
| Sebastiani, Paola; Thyagarajan, Bharat; Sun, Fangui et al. (2017) Biomarker signatures of aging. Aging Cell 16:329-338 |
| Sebastiani, Paola; Gurinovich, Anastasia; Bae, Harold et al. (2017) Four Genome-Wide Association Studies Identify New Extreme Longevity Variants. J Gerontol A Biol Sci Med Sci 72:1453-1464 |
| Sebastiani, Paola; Gurinovich, Anastasia; Bae, Harold et al. (2017) Assortative Mating by Ethnicity in Longevous Families. Front Genet 8:186 |
| Macé, Aurélien; Tuke, Marcus A; Deelen, Patrick et al. (2017) CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits. Nat Commun 8:744 |
| Perls, Thomas T (2017) Male Centenarians: How and Why Are They Different from Their Female Counterparts? J Am Geriatr Soc 65:1904-1906 |
| Pedersen, Jacob K; Elo, Irma T; Schupf, Nicole et al. (2017) The Survival of Spouses Marrying Into Longevity-Enriched Families. J Gerontol A Biol Sci Med Sci 72:109-114 |
| Sebastiani, Paola; Bae, Harold; Gurinovich, Anastasia et al. (2017) Limitations and risks of meta-analyses of longevity studies. Mech Ageing Dev 165:139-146 |
| Fagan, Erin; Sun, Fangui; Bae, Harold et al. (2017) Telomere length is longer in women with late maternal age. Menopause 24:497-501 |
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