Improved Health-Span and Lifespan in mtDNA Mutator Mice Treated With the Mitochondrially Targeted Antioxidant SkQ1

Aging (Albany NY). 2017 Feb 15;9(2):315-339. doi: 10.18632/aging.101174.

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.

Keywords: brown adipose tissue; cardiolipin; longevity; mitochondria; oxidative stress; reactive oxygen species; thermogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Aging / drug effects*
  • Aging / metabolism
  • Animals
  • Body Temperature / physiology
  • Body Weight / physiology
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism*
  • Heart / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Longevity / drug effects*
  • Longevity / physiology
  • Mice
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Mutation*
  • Myocardium / metabolism
  • Plastoquinone / analogs & derivatives*
  • Plastoquinone / pharmacology
  • Reactive Oxygen Species / metabolism

Substances

  • 10-(6'-plastoquinonyl)decyltriphenylphosphonium
  • DNA, Mitochondrial
  • Reactive Oxygen Species
  • Plastoquinone