Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue

Nicolai Treiber, Pallab Maity, Karmveer Singh, Matthias Kohn, Alexander F Keist, Florentina Ferchiu, Lea Sante, Sebastian Frese, Wilhelm Bloch, Florian Kreppel, Stefan Kochanek, Anca Sindrilaru, Sebastian Iben, Josef Högel, Michael Ohnmacht, Lutz E Claes, Anita Ignatius, Jin H Chung, Min J Lee, York KamenischMark Berneburg, Thorsten Nikolaus, Kerstin Braunstein, Anne-Dorte Sperfeld, Albert C Ludolph, Karlis Briviba, Meinhard Wlaschek, Lore Florin, Peter Angel, Karin Scharffetter-Kochanek

Publication: Contribution to journalJournal articlesResearch


The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue-specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16(INK4a) , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue-specific anti-aging strategies.

Original languageEnglish
JournalAging cell
Issue number2
Pages (from-to)239-254
Number of pages16
Publication statusPublished - 01.04.2011

Research areas and keywords

  • Aging
  • Animals
  • Biological Markers
  • Bone and Bones
  • Cells, Cultured
  • Connective Tissue
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Fibroblasts
  • Humans
  • Kyphosis
  • Longevity
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria
  • Muscle, Skeletal
  • Phenotype
  • Reactive Oxygen Species
  • Skin
  • Superoxide Dismutase
  • Superoxides


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