Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
PLoS One. 2010 Jun 10;5(6):e11069. doi: 10.1371/journal.pone.0011069.
Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. Mitochondrial genetic variation may contribute to altered susceptibility to the frailty syndrome in older adults.
METHODOLOGY/PRINCIPAL FINDINGS: To assess potential mitochondrial genetic contributions to the likelihood of frailty, mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study (1989-1990, 1992-1993). At baseline, frailty was identified as the presence of three or more of five indicators (weakness, slowness, shrinking, low physical activity, and exhaustion). mtDNA variation was assessed in a pilot study, including 315 individuals selected as extremes of the frailty phenotype, using an oligonucleotide sequencing microarray based on the Revised Cambridge Reference Sequence. Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons: mt146, mt204, and mt228. In addition to pilot participants, 4,459 additional men and women with frailty classifications, and an overlapping subset of 4,453 individuals with grip strength measurements, were included in the study population genotyped at mt204 and mt228. In the study population, the mt204 C allele was associated with greater likelihood of frailty (adjusted odds ratio = 2.04, 95% CI = 1.07-3.60, p = 0.020) and lower grip strength (adjusted coefficient = -2.04, 95% CI = -3.33- -0.74, p = 0.002).
This study supports a role for mitochondrial genetic variation in the frailty syndrome and later life muscle strength, demonstrating the importance of the mitochondrial genome in complex geriatric phenotypes.
线粒体参与细胞代谢、活性氧物质生成和细胞凋亡途径的动态变化。因此，人们推测线粒体功能可能会影响老年人的功能下降和对疾病的易感性。线粒体遗传变异可能会导致老年人易患虚弱综合征。
方法/主要发现：为了评估线粒体遗传变异对虚弱发生的潜在影响，比较了虚弱和非虚弱老年人的线粒体 DNA（mtDNA）变异。还探讨了选定 SNP 与肌肉力量表型的关联。参与者选自心血管健康研究（CHS），这是一项基于人群的观察性研究（1989-1990 年，1992-1993 年）。在基线时，虚弱被定义为存在五个指标中的三个或更多（虚弱、缓慢、萎缩、体力活动少和疲惫）。在一项试点研究中，使用基于修订后的剑桥参考序列的寡核苷酸测序微阵列评估了 mtDNA 变异，该研究包括 315 名根据虚弱表型选择的极端个体。在所有试点参与者或按性别分层比较中，三个 mtDNA SNP 与虚弱显著相关：mt146、mt204 和 mt228。除了试点参与者外，还纳入了 4459 名具有虚弱分类的男性和女性以及 4453 名具有握力测量值的重叠子集，在 mt204 和 mt228 进行基因分型的研究人群中。在研究人群中，mt204 的 C 等位基因与虚弱的可能性更大相关（调整后的优势比=2.04，95%CI=1.07-3.60，p=0.020）和较低的握力（调整系数=-2.04，95%CI=-3.33- -0.74，p=0.002）。
这项研究支持线粒体遗传变异在虚弱综合征和晚年肌肉力量中的作用，证明了线粒体基因组在复杂老年表型中的重要性。
