Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1

Irina G. Shabalina; Mikhail Yu. Vyssokikh; Natalia Gibanova; Robert I. Csikasz; Daniel Edgar; Anne Hallden-Waldemarson; Zinaida Rozhdestvenskaya; Lora E. Bakeeva; Valeria B. Vays; Antonina V. Pustovidko; Maxim V. Skulachev; Barbara Cannon; Vladimir P. Skulachev; Jan Nedergaard

doi:doi:10.18632/aging.101174

Research Paper Volume 9, Issue 2 pp 315—339

Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1

Irina G. Shabalina^1,, Mikhail Yu. Vyssokikh^2,, Natalia Gibanova^1,, Robert I. Csikasz^1,, Daniel Edgar^1,4,, Anne Hallden-Waldemarson^1,, Zinaida Rozhdestvenskaya^1,, Lora E. Bakeeva^2,3,, Valeria B. Vays^2,, Antonina V. Pustovidko^2,, Maxim V. Skulachev^3,, Barbara Cannon^1,, Vladimir P. Skulachev^2,3,, Jan Nedergaard^1,,

¹ The Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden
² The Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russian Federation
³ Institute of Mitoengineering, Moscow State University, 119992, Moscow, Russian Federation
⁴ Present address: Buck Institute for research on aging, Novato, CA 94945, USA

Received: December 30, 2016 Accepted: February 3, 2017 Published: February 15, 2017

https://doi.org/10.18632/aging.101174
How to Cite

Cite this Article

How to cite

Shabalina IG, Vyssokikh MY, Gibanova N, Csikasz RI, Edgar D, Hallden-Waldemarson A, Rozhdestvenskaya Z, Bakeeva LE, Vays VB, Pustovidko AV, Skulachev MV, Cannon B, Skulachev VP, et al, . Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1. Aging (Albany NY). 2017; 9:315-339. https://doi.org/10.18632/aging.101174

Copy or Download citation:

Select the format you require from the list below

Plain text
EndNote
Reference Manager
ProCite
BibteX

Provider: 
        TY  - JOUR
        AU  - Shabalina, Irina G. 
        AU  - Vyssokikh, Mikhail Yu. 
        AU  - Gibanova, Natalia 
        AU  - Csikasz, Robert I. 
        AU  - Edgar, Daniel 
        AU  - Hallden-Waldemarson, Anne 
        AU  - Rozhdestvenskaya, Zinaida 
        AU  - Bakeeva, Lora E. 
        AU  - Vays, Valeria B. 
        AU  - Pustovidko, Antonina V. 
        AU  - Skulachev, Maxim V. 
        AU  - Cannon, Barbara 
        AU  - Skulachev, Vladimir P. 
        AU  - Nedergaard, Jan 
        TI  - Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 9
        IS  - 2
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.101174
        DO  - 10.18632/aging.101174
        SP  - 315
        EP  - 339
        PY  - 
        AB  - MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions. SkQ1 counteracts this as it scavenges mitochondrial ROS. As the results, the normal mitochondrial ultrastructure is preserved in liver and heart; the phosphorylation capacity of skeletal muscle mitochondria as well as the thermogenic capacity of brown adipose tissue is also improved. The SkQ1-treated mice live significantly longer (335 versus 290 days). These data may be relevant in relation to treatment of mitochondrial diseases particularly and the process of aging in general.
        ER  -

Click to copy this citation from the text box above or download the citation:

Abstract

MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions. SkQ1 counteracts this as it scavenges mitochondrial ROS. As the results, the normal mitochondrial ultrastructure is preserved in liver and heart; the phosphorylation capacity of skeletal muscle mitochondria as well as the thermogenic capacity of brown adipose tissue is also improved. The SkQ1-treated mice live significantly longer (335 versus 290 days). These data may be relevant in relation to treatment of mitochondrial diseases particularly and the process of aging in general.

Research Paper Volume 9, Issue 2 pp 315—339

Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1

Received: December 30, 2016 Accepted: February 3, 2017 Published: February 15, 2017

Abstract

Corresponding Authors

Keywords