Toggle Main Menu Toggle Search

Open Access padlockePrints

Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations

Lookup NU author(s): Dr Brendan Payne, Dr Ian Wilson, Professor Rita Horvath, Dr Mauro Santibanez Koref, Dr David Samuels, Dr David Price, Professor Patrick Chinnery

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

There is emerging evidence that people with successfully treated HIV infection age prematurely, leading to progressive multi-organ disease(1), but the reasons for this are not known. Here we show that patients treated with commonly used nucleoside analog anti-retroviral drugs progressively accumulate somatic mitochondrial DNA (mtDNA) mutations, mirroring those seen much later in life caused by normal aging(2,3). Ultra-deep re-sequencing by synthesis, combined with single-cell analyses, suggests that the increase in somatic mutation is not caused by increased mutagenesis but might instead be caused by accelerated mtDNA turnover. This leads to the clonal expansion of preexisting age-related somatic mtDNA mutations and a biochemical defect that can affect up to 10% of cells. These observations add weight to the role of somatic mtDNA mutations in the aging process and raise the specter of progressive iatrogenic mitochondrial genetic disease emerging over the next decade.


Publication metadata

Author(s): Payne BAI, Wilson IJ, Hateley CA, Horvath R, Santibanez-Koref M, Samuels DC, Price DA, Chinnery PF

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2011

Volume: 43

Issue: 8

Pages: 806-U121

Print publication date: 26/06/2011

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.863

DOI: 10.1038/ng.863


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share