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Lifespan effects of mitochondrial mutations

Nature volume 540, pages E13–E14 (2016)Cite this article

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arising from A. Latorre-Pellicer et al. Nature 535, 561–565 (2016); doi:10.1038/nature18618

Somatic mitochondrial DNA (mtDNA) mutations accumulate within various tissues with age1,2, however evidence directly showing the influence of mtDNA natural variations on ageing has been limited to date. Recently, Latorre-Pellicer et al. demonstrated that polymorphisms within mtDNA affect reactive oxygen species (ROS) levels, body mass, ageing score, tumour incidence and lifespan of conplastic mice3. Here we show that similarly generated conplastic strains, which carry a nuclear Nnt mutation, do not show any alterations in these parameters, demonstrating the relevance of specific mitonuclear interactions in determining mammalian healthspan through increased production of ROS.

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Figure 1: Healthspan study in the conplastic strain C57BL/6J-mtNZB/BlnJ (mtNZB/BlnJ) and in C57BL/6J (mtC57BL/6J) control mice.

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Author information

Authors and Affiliations

  1. Lübeck Institute of Experimental Dermatology, University of Lübeck, Germany

    Misa Hirose, Paul Schilf, Yask Gupta & Saleh M. Ibrahim

  2. Institute of Medical Biometry and Statistics, University of Lübeck, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany

    Marvin N. Wright, Marvin N. Wright & Andreas Ziegler

  3. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany

    Olaf Jöhren

  4. Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

    Olaf Jöhren

  5. Institute of Nutritional Medicine, University of Lübeck, Lübeck, Germany

    Anika E. Wagner & Christian Sina

  6. ZKS Lübeck, University of Lübeck, Lübeck, Germany

    Andreas Ziegler

  7. School of Mathematics, Statistics and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa

    Andreas Ziegler

  8. Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach, Switzerland

    Michael Ristow

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  1. Misa Hirose
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  2. Paul Schilf
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Contributions

M.H. and S.M.I. designed the study. M.H., P.S. and C.S. performed the experiments and analysed the data. M.W. and A.Z. conducted the statistical analysis of the survival data. Y.G. analysed the sequencing data. O.J. performed the indirect calorimetric cage experiment and analysed the data. M.H., A.E.W., M.R. and S.M.I. wrote the manuscript with contributions from all other authors. S.M.I. directed the study.

Corresponding author

Correspondence to Saleh M. Ibrahim.

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Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Indirect calorimetric cage analysis of mtC57BL/6J and mtNZB/BlnJ mice.

a, Spontaneous locomotor activities. b, Area under the curve analysis of the activities shown in a. c, Area under the curve of respiratory exchange ratio (RER) and energy expenditure (EE). Data were obtained from 5 female mtC57BL/6J mice and 6 female mtNZB/BlnJ mice.

Extended Data Table 1 Statistical analysis for the lifespan of mtC57BL/6J and mtNZB/BlnJ mice
Full size table
Extended Data Table 2 Sequence difference between mtDNA of mtNZB/BlnJ and mtC57BL/6J mice
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Supplementary information

Supplementary Information

This file contains Supplementary Data Table 1, Supplementary Methods and Supplementary References. (PDF 215 kb)

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Hirose, M., Schilf, P., Gupta, Y. et al. Lifespan effects of mitochondrial mutations. Nature 540, E13–E14 (2016). https://doi.org/10.1038/nature20778

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