Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Mayo Graduate School, Neuroscience Track, Mayo Clinic, Jacksonville, FL, USA.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL 32224, USA.
Mitochondrion. 2024 Sep;78:101948. doi: 10.1016/j.mito.2024.101948. Epub 2024 Aug 22.
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.
线粒体健康是衰老的一个重要因素,已知线粒体功能障碍随着年龄的增长而增加,并导致与年龄相关的神经退行性疾病的发展。此外,线粒体基因组 (mtDNA) 已被证明会在衰老过程中获得潜在的有害体细胞变异,而 mtDNA 单核苷酸多态性 (SNP) 已被证明对各种神经退行性疾病既有保护作用也有损害作用。然而,关于 mtDNA 变异在长寿和成功的神经衰老中的作用知之甚少。在这项研究中,我们研究了线粒体单倍群形式的 mtDNA SNPs 与 1405 名无神经疾病的健康受试者成功神经衰老之间的关联。尽管在进行多次测试校正后(认为 P<0.0017 为显著)并不显著,但我们检测到 I 单倍群(N=45,3.2%)与更年轻的年龄之间存在名义上的显著关联(β:-5.00,P=0.006),表明该单倍群在年龄较大的神经健康个体中较少出现,可能与生存能力下降有关。在独立的神经健康队列中复制这一发现,对于我们理解健康神经衰老的生物学过程至关重要。