Associations of mitochondrial genomic variation with successful neurological aging

Mitochondrial health is an integral factor in aging, with mitochondrial dysfunction known to increase with age and contribute to the development of age-related neurodegenerative disorders. Additionally, the mitochondrial genome (mtDNA) has been shown to acquire potentially damaging somatic variation as part of the aging process, while mtDNA single nucleotide polymorphism (SNPs) have been shown to be both protective and detrimental for various neurodegenerative diseases. Yet, little is known about the involvement of mtDNA variation in longevity and successful neurological aging. In this study, we examined the association of mtDNA SNPs, in the form of mitochondrial haplogroups, with successful neurological aging in 1,405 unrelated neurologically healthy subjects. Although not quite significant after correcting for multiple testing (P < 0.0017 considered as significant), we detected a nominally significant association between the I haplogroup (N = 45, 3.2 %) and a younger age (β: -5.00, P = 0.006), indicating that this haplogroup is observed less frequently in older neurologically healthy individuals and may be associated with decreased survival. Replication of this finding in independent neurologically healthy cohorts will be imperative for shaping our understanding of the biological processes underlying healthy neurological aging.