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Mitochondrial function and mitochondrial DNA maintenance with advancing age

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Abstract

We review the impact of mitochondrial DNA (mtDNA) maintenance and mitochondrial function on the aging process. Mitochondrial function and mtDNA integrity are closely related. In order to create a protective barrier against reactive oxygen and nitrogen species (RONS) attacks and ensure mtDNA integrity, multiple cellular mtDNA copies are packaged together with various proteins in nucleoids. Regulation of antioxidant and RONS balance, DNA base excision repair, and selective degradation of damaged mtDNA copies preserves normal mtDNA quantities. Oxidative damage to mtDNA molecules does not substantially contribute to increased mtDNA mutation frequency; rather, mtDNA replication errors of DNA PolG are the main source of mtDNA mutations. Mitochondrial turnover is the major contributor to maintenance of mtDNA and functionally active mitochondria. Mitochondrial turnover involves mitochondrial biogenesis, mitochondrial dynamics, and selective autophagic removal of dysfunctional mitochondria (i.e., mitophagy). All of these processes exhibit decreased activity during aging and fall under greater nuclear genome control, possibly coincident with the emergence of nuclear genome instability. We suggest that the age-dependent accumulation of mutated mtDNA copies and dysfunctional mitochondria is associated primarily with decreased cellular autophagic and mitophagic activity.

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Acknowledgments

We would like to thank Margaret Ilina for her assistance with manuscript preparation. This work was partly supported by the Basic Sciences to Medicine program of the Presidium of the Russian Academy of Sciences (grant FSM-G12) and by the Institute of Theoretical and Experimental Biophysics RAS.

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  1. Institute of Theoretical and Experimental Biophysics of Russian Academy of Sciences, Institute St. 3, Pushchino, Moscow, 142290, Russia

    Azhub I. Gaziev & Serzh Abdullaev

  2. Center for Alaska Native Health Research, University of Alaska Fairbanks, 902 N. Koyukuk, Room 311, Fairbanks, AK, 99775-7000, USA

    Andrej Podlutsky

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  1. Azhub I. Gaziev
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Gaziev, A.I., Abdullaev, S. & Podlutsky, A. Mitochondrial function and mitochondrial DNA maintenance with advancing age. Biogerontology 15, 417–438 (2014). https://doi.org/10.1007/s10522-014-9515-2

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