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Independent impacts of aging on mitochondrial DNA quantity and quality in humans

Ruoyu Zhang; Yiqin Wang; Kaixiong Ye; Martin Picard; Zhenglong Gu

Title:
Independent impacts of aging on mitochondrial DNA quantity and quality in humans
Author(s):
Zhang, Ruoyu
Wang, Yiqin
Ye, Kaixiong
Picard, Martin
Gu, Zhenglong
Date:
Type:
Articles
Department(s):
Psychiatry
Neurology
Volume:
18
Persistent URL:
Book/Journal Title:
BMC Genomics
Notes:
Aging, Heteroplasmy, mtDNA copy number, Whole genome sequencing
Abstract:
Background The accumulation of mitochondrial DNA (mtDNA) mutations, and the reduction of mtDNA copy number, both disrupt mitochondrial energetics, and may contribute to aging and age-associated phenotypes. However, there are few genetic and epidemiological studies on the spectra of blood mtDNA heteroplasmies, and the distribution of mtDNA copy numbers in different age groups and their impact on age-related phenotypes. In this work, we used whole-genome sequencing data of isolated peripheral blood mononuclear cells (PBMCs) from the UK10K project to investigate in parallel mtDNA heteroplasmy and copy number in 1511 women, between 17 and 85 years old, recruited in the TwinsUK cohorts. Results We report a high prevalence of pathogenic mtDNA heteroplasmies in this population. We also find an increase in mtDNA heteroplasmies with age (β = 0.011, P = 5.77e-6), and showed that, on average, individuals aged 70-years or older had 58.5% more mtDNA heteroplasmies than those under 40-years old. Conversely, mtDNA copy number decreased by an average of 0.4 copies per year (β = −0.395, P = 0.0097). Multiple regression analyses also showed that age had independent effects on mtDNA copy number decrease and heteroplasmy accumulation. Finally, mtDNA copy number was positively associated with serum bicarbonate level (P = 4.46e-5), and inversely correlated with white blood cell count (P = 0.0006). Moreover, the aggregated heteroplasmy load was associated with blood apolipoprotein B level (P = 1.33e-5), linking the accumulation of mtDNA mutations to age-related physiological markers. Conclusions Our population-based study indicates that both mtDNA quality and quantity are influenced by age. An open question for the future is whether interventions that would contribute to maintain optimal mtDNA copy number and prevent the expansion of heteroplasmy could promote healthy aging.
Subject(s):
Genomics
Nucleotide sequence
Aging
Mitochondrial DNA
Biology
Publisher DOI:
https://doi.org/10.1186/s12864-017-4287-0
Item views
16
Metadata:
text | xml
Suggested Citation:
Ruoyu Zhang, Yiqin Wang, Kaixiong Ye, Martin Picard, Zhenglong Gu, , Independent impacts of aging on mitochondrial DNA quantity and quality in humans, Columbia University Academic Commons, .

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