Although SA is a complex and multifactorial trait, its sub-domains (chronological age, physical function, cognitive health, and social engagement and well- being) have strong genetic components. Centenarians cluster in families and siblings of centenarians are more likely to live past 85 years than others in their birth cohorts (Perls et al. 2002). Finally, data suggest that several domains underlying SA are heritable in- cluding: longevity, grip strength, lower extremity function, and retention of cognitive ability (Carmelli

studies of population isolates such as the Amish have multiple advantages over other study designs because they represent well-ascertained multigenerational ped- igrees obtained from relatively few founders and span- ning few generations, resulting in both environmental and phenotypic homogeneity (Arcos-Burgos and Muenke 2002). The results of this study suggest that several regions of interest in the genome might harbor SA loci, with the strongest evidence implicating the FRA6E region of chromosome 6.

only exclusion criterion for the SA arm of the study was cognitive impairment (individuals screening cognitively impaired were referred to the dementia arm of the study). The recruitment and ascertainment methods for CAMP have been previously described (Pericak-Vance et al. 1996; Velez Edwards et al. 2011).

Using an all common paths query of the Anabap- tist Genealogy Database, all 263 individuals were placed in a 13-generation, 4,998 person pedigree (Agarwala et al. 2003). There is no evidence of a more recent founder effect among the SA individuals. The first individuals in this pedigree born in Indiana or Ohio were born in the 1820s, four to five generations before the oldest sampled individuals in this study.

Study population

Definition of successful aging Successful aging was defined according to tests and measurements taken at the time of baseline enrollment in the study. SA was defined as previously described (Velez Edwards et al. 2011), considering functioning in all three domains described by Rowe and Kahn (1997). The specific criteria we used are outlined in Table 1. The first requirement was survival to age 80. All individuals had to be cognitively intact (education-adjusted mod- ified mini-mental state examination (3MS) >86). If someone had an education-adjusted 3MS <87 but was determined not to be cognitively impaired after further neuropsychological testing and evaluation at a consensus conference (Hahs et al. 2006), they would be classified as SA if they met the other criteria. SA individuals did not have significant depressive

This study is a part of the larger ongoing Collaborative Aging and Memory Project (CAMP). CAMP is a multi-institutional prospective population-based study of aging and dementia in the Amish communities of Adams, Elkhart, and LaGrange counties in Indiana and Holmes County in Ohio, conducted from 2002 until the present. These communities were formed in several waves of migration in the eighteenth and nineteenth centuries (van der Walt et al. 2005). The Amish originally emigrated from Europe to Pennsyl- vania in the 1700s, and a further westward expansion of the Amish population occurred in the early 1800s when a subset of the Pennsylvania population migrat- ed to Ohio and Indiana. A second wave of migration from Switzerland arrived in the nineteenth century, eventually settling in Adams County, Indiana, in the 1850s. Present-day Amish in Holmes County, Ohio and Elkhart and LaGrange counties, Indiana are large- ly descended from the first wave of westward immi- gration from Pennsylvania, while the Adams County, Indiana settlements are largely descended from the second wave of immigration that passed through Pennsylvania (van der Walt et al. 2005). Both sets of communities, therefore, have a degree of shared his- tory and ancestry with the Pennsylvania Amish com- munities. Written and informed consent was obtained for all participants and their legal guardians.

Table 1 Criteria to identify “successfully aged” individuals

Criteria Test/cutoff Age >80 Cognitively intact 3MS >86 (education- adjusted) No significant depressive symptoms GDS <6 “High function” self-reported measures of 0 or 1 ADL and physical function IADL scales 0 or 1 Nagi score 3 or 4 Rosow– Breslau score Lower extremity function >8 (12 pt scale) EPESE Satisfied or very satisfied with life Questionnaire

For the SA arm of the CAMP study, individuals over age 80 were identified through public directories published by individual Amish communities and re- ferral from individuals already enrolled in the study. Once individuals were identified, a door-to-door inter- view was performed for a baseline examination. The

Self-rated physical function was assessed by several well-established instruments. Basic self-care was assessed using a modified Katz ADL scale con- sisting of eight items: bathing, dressing, grooming, toileting, continence, transferring, walking, and eating (Katz 1983). Difficulty with musculoskeletal function was assessed by a five-item scale based on the work of Nagi (1976) used in the EPESE (Seeman et al. 1994): pushing large objects, stoop- ing or kneeling, carrying weights over 10 lb, extending arms above shoulder level, and writing. Advanced daily living tasks were evaluated by a – three-item modified Rosow Breslau scale (Rosow and Breslau 1966) assessing difficulty performing heavy work around the house or farm, walking up and down a flight of stairs, and walking a half mile without help. A final scale assessing more integrative functions IADLs consisted of six of the eight items suggested by Lawton and Brody (1969): traveling, shopping, preparing meals, doing housework, managing medications, and handling money.