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.