Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.

Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tis...

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Main Authors: Shinichi Someya, Gregory C Kujoth, Mi-Jung Kim, Timothy A Hacker, Marc Vermulst, Richard Weindruch, Tomas A Prolla
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171159&type=printable
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author Shinichi Someya
Gregory C Kujoth
Mi-Jung Kim
Timothy A Hacker
Marc Vermulst
Richard Weindruch
Tomas A Prolla
author_facet Shinichi Someya
Gregory C Kujoth
Mi-Jung Kim
Timothy A Hacker
Marc Vermulst
Richard Weindruch
Tomas A Prolla
author_sort Shinichi Someya
collection DOAJ
description Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation.
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spelling doaj-art-d0cf2fabc2cc46abae69badfebb375fe2025-08-20T03:12:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017115910.1371/journal.pone.0171159Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.Shinichi SomeyaGregory C KujothMi-Jung KimTimothy A HackerMarc VermulstRichard WeindruchTomas A ProllaMitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice. Long-term CR did not increase the median or maximum lifespan of PolgD257A/D257A mice. Furthermore, CR did not reduce mtDNA deletions in the heart and muscle, accelerated sarcopenia, testicular atrophy, nor improve the alterations in cardiac parameters that are present in aged mitochondrial mutator mice. Therefore, our findings suggest that accumulation of mtDNA mutations may interfere with the beneficial action of CR in aging retardation.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171159&type=printable
spellingShingle Shinichi Someya
Gregory C Kujoth
Mi-Jung Kim
Timothy A Hacker
Marc Vermulst
Richard Weindruch
Tomas A Prolla
Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
PLoS ONE
title Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
title_full Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
title_fullStr Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
title_full_unstemmed Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
title_short Effects of calorie restriction on the lifespan and healthspan of POLG mitochondrial mutator mice.
title_sort effects of calorie restriction on the lifespan and healthspan of polg mitochondrial mutator mice
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0171159&type=printable
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