A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects

Niemi, Anna Kaisa; Moilanen, Jukka S.; Tanaka, Masashi; Hervonen, Antti; Hurme, Mikko; Lehtimäki, Terho; Arai, Yasumichi; Hirose, Nobuyoshi; Majamaa, Kari

doi:10.1038/sj.ejhg.5201308

Cited by 114 publications

(81 citation statements)

References 20 publications

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“…The 150C3 T replacement was originally reported in Italian centenarians (19). Also, we reported this replacement to be associated with healthy longevity in both Finland and Japan (20). Thus, the 150C3 T might confer resistance against metabolic syndrome in women.…”

Section: Discussionmentioning

confidence: 90%

Women With Mitochondrial Haplogroup N9a Are Protected Against Metabolic Syndrome

et al. 2007

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Section: Discussionmentioning

confidence: 90%

Women With Mitochondrial Haplogroup N9a Are Protected Against Metabolic Syndrome

et al. 2007

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“…17 The m.10398A > G variant that was associated with a decreased adiponectin on ART results in a threonine to alanine amino acid change in the NADH dehydrogenase subunit 3 of Complex I, and alters in vitro mitochondrial measures (e.g., mitochondrial matrix pH and calcium concentration). 29 It has also been studied in human diseases and aging, 30,31 but risk associations have been inconsistent. In a Chinese population, this variant was associated with an increased risk for metabolic syndrome.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Hulgan

Stein

Cotter

et al. 2013

AIDS Research and Human Retroviruses

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Studies in persons of European descent have suggested that mitochondrial DNA (mtDNA) haplogroups influence antiretroviral therapy (ART) toxicity. We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white, ART-naive subjects starting ART. A5152s was a substudy of A5142, a randomized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs), or both without NRTIs. Brachial artery flow-mediated dilation (FMD) and cardiovascular biomarker assessments were performed at baseline and at weeks 4 and 24. Ten haplogroup-defining mtDNA polymorphisms were determined. FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests. Thirty-nine non-Hispanic white participants had DNA and 24-week data. The nonsynonymous m.10398A > G mtDNA polymorphism (N = 8) was associated with higher median baseline adiponectin (5.0 vs. 4.2 lg/ml; p = 0.003), greater absolute ( -1.9 vs. -0.2 lg/ml) and relative ( -33% vs. -3%) adiponectin decreases ( p < 0.001 for both), and lower week 24 brachial artery FMD (3.6% vs. 5.4%; p = 0.04). Individual mtDNA haplogroups, including haplogroups H (N = 13) and U (N = 6), were not associated with adiponectin or FMD changes. In this small pilot study, adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases. These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects. Validation studies in larger populations and in different racial/ethnic groups that include m.10398G carriers are needed.

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“…Thus, mtDNA is likely to play a role in adaptive evolution. However, our knowledge of its influence on phenotypic variation is still very incomplete (for recent reviews see Rand et al 2004;Ballard and Whitlock 2004;Gemmel et al 2004;Ballard and Rand 2005).Mitochondrial DNA has also been suggested to play an important role in the evolution of aging (Harman 1956;Tanaka et al 1998; de Benedicts et al 2000;Niemi et al 2005; reviewed in Ballard and Whitlock 2004). Products of mtDNA clearly have a profound role in energy metabolism.…”

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Within-Population Variation in Cytoplasmic Genes Affects Female Life Span and Aging in Drosophila Melanogaster

et al. 2006

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Abstract. It has been suggested that mitochondrial DNA (mtDNA) may play an important role in aging. Yet, few empirical studies have tested this hypothesis, partly because the degree of sequence polymorphism in mtDNA is assumed to be low. However, low sequence variation may not necessarily translate into low phenotypic variation. Here, we report an experiment that tests whether there is within-population variation in cytoplasmic genes for female longevity and senescence. To achieve this, we randomly selected 25 ''mitochondrial founders'' from a single, panmictic population of Drosophila melanogaster and used these founders to generate distinct ''mt'' lines in which we controlled for the nuclear background by successive backcrossing. Potential confounding effects of cytoplasmically transmitted bacteria were eliminated by tetracycline treatment. The mt lines were then assayed for differences in longevity, Gompertz intercept (frailty), and demographic rate of change in mortality with age (rate-of-senescence) in females. We found significant cytoplasmic effects on all three variables. This provides evidence that genetic variation in cytoplasmic genes, presumably mtDNA, contributes to variation in female mortality and aging. Genetic variation in the mitochondrial genome has traditionally been considered selectively neutral. Consequently, sequence divergence in mitochondrial DNA (mtDNA) has been used extensively as a tool to infer evolutionary histories, with the assumption that mtDNA evolves solely by accumulating neutral mutations (see Gemmel et al. 2004;Ballard and Rand 2005). However, this traditional view of the mitochondrial genome is currently changing. In fact, non-neutral evolution of mtDNA has now been implied in several recent studies demonstrating that specific cytoplasmic gene products exhibit reduced or altered function when coexpressed in nuclear genomes derived from different populations (reviewed in Rand 2001;Rand et al. 2004;Ballard and Rand 2005). Thus, mtDNA is likely to play a role in adaptive evolution. However, our knowledge of its influence on phenotypic variation is still very incomplete (for recent reviews see Rand et al. 2004;Ballard and Whitlock 2004;Gemmel et al. 2004;Ballard and Rand 2005).Mitochondrial DNA has also been suggested to play an important role in the evolution of aging (Harman 1956;Tanaka et al. 1998; de Benedicts et al. 2000;Niemi et al. 2005; reviewed in Ballard and Whitlock 2004). Products of mtDNA clearly have a profound role in energy metabolism. Because variation in metabolic rate may be associated with variation in life span (e.g., Sacher 1977), genetic variation in mtDNA could conceivably affect both metabolism and aging (Beckman and Ames 1998; Speakman 2005). Currently, empirical evidence for an association between metabolic rate and aging is limited (Brand 2000;Speakman et al. 2004). Khazaeli et al. (2005) found no relationship between metabolic rate and survival in Drosophila melanogaster lines artificially selected for increased life span. However, the results of ...

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A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects

Cited by 114 publications

References 20 publications

Women With Mitochondrial Haplogroup N9a Are Protected Against Metabolic Syndrome

Women With Mitochondrial Haplogroup N9a Are Protected Against Metabolic Syndrome

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Within-Population Variation in Cytoplasmic Genes Affects Female Life Span and Aging in Drosophila Melanogaster

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