Mitochondrial haplogroup X is associated with successful aging in the Amish.

Avoiding disease, maintaining physical and cognitive function, and continued social engagement in long-lived individuals describe successful aging (SA). Mitochondrial lineages described by patterns of common genetic variants ("haplogroups") have been associated with increased longevity in different populations. We investigated the influence of mitochondrial haplogroups on SA in an Amish community sample. Cognitively intact volunteers aged ≥80 years (n = 261) were enrolled in a door-to-door survey of Amish communities in Indiana and Ohio. Individuals scoring in the top third for lower extremity function, needing little assistance with self-care tasks, having no depression symptoms, and expressing high life satisfaction were considered SA (n = 74). The remainder (n = 187) were retained as controls. These individuals descend from 51 matrilines in a single 13-generation pedigree. Mitochondrial haplogroups were assigned using the ten mitochondrial single nucleotide polymorphisms (mtSNPs) defining the nine most common European haplogroups. An additional 17 mtSNPs from a genome-wide association panel were also investigated. Associations between haplogroups, mtSNPs, and SA were determined by logistic regression models accounting for sex, age, body mass index, and matriline via generalized estimating equations. SA cases were more likely to carry Haplogroup X (OR = 7.56, p = 0.0015), and less likely to carry Haplogroup J (OR = 0.40, p = 0.0003). Our results represent a novel association of Haplogroup X with SA and suggest that variants in the mitochondrial genome may promote maintenance of both physical and cognitive function in older adults.

Linkage and association of successful aging to the 6q25 region in large Amish kindreds.

Successful aging (SA) is a multidimensional phenotype involving living to older age with high physical function, preserved cognition, and continued social engagement. Several domains underlying SA are heritable, and identifying health-promoting polymorphisms and their interactions with the environment could provide important information regarding the health of older adults. In the present study, we examined 263 cognitively intact Amish individuals age 80 and older (74 SA and 189 "normally aged") all of whom are part of a single 13-generation pedigree. A genome-wide association study of 630,309 autosomal single nucleotide polymorphisms (SNPs) was performed and analyzed for linkage using multipoint analyses and for association using the modified quasi-likelihood score test. There was evidence for linkage on 6q25-27 near the fragile site FRA6E region with a dominant model maximum multipoint heterogeneity LOD score = 3.2. The 1-LOD-down support interval for this linkage contained one SNP for which there was regionally significant evidence of association (rs205990, p = 2.36 × 10(-5)). This marker survived interval-wide Bonferroni correction for multiple testing and was located between the genes QKI and PDE10A. Other areas of chromosome 6q25-q27 (including the FRA6E region) contained several SNPs associated with SA (minimum p = 2.89 × 10(-6)). These findings suggest potentially novel genes in the 6q25-q27 region linked and associated with SA in the Amish; however, these findings should be verified in an independent replication cohort.