Lifespan extension in the spontaneous dwarf rat and enhanced resistance to hyperoxia-induced mortality

Toru Sasaki, Shoichi Tahara, Tadashi Shinkai, Kazunao Kuramoto, Shigenobu Matsumoto, Makoto Yanabe, Shohei Takagi, Hiroshi Kondo, Takao Kaneko

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Lifespan extension has been demonstrated in dwarfism mouse models relative to their wild-type. The spontaneous dwarf rat (SDR) was isolated from a closed colony of Sprague-Dawley (SD) rats. Growth hormone deficiencies have been indicated to be responsible for dwarfism in SDR. Survival time, the markers of oxidative stress, antioxidant enzymes, and resistance to hyperoxia were compared between SDR and SD rats, to investigate whether SDR, a dwarfism rat model, also extends lifespan and has an enhanced resistance to oxidative stress.SDRs lived 38% longer than SD rats on average. This is the first report to show that dwarf rats exhibit lifespan extensions similar to Ames and Snell mice. Decreased 8-oxo-2'-deoxyguanosine (8-oxodG) content, a marker of oxidative DNA damage, indicated suppressed oxidative stress in the liver, kidney, and lung of SDRs. Increased glutathione peroxidase enzyme activity was consistent with decreased 8-oxodG content in the same tissues. The heart and brain showed a similar tendency, but this was not significant. However, the catalase and superoxide dismutase enzyme activities of SDRs were not different from those of SD rats in any tissue. This was not what the original null hypothesis predicted. SDRs had potent resistance to the toxicity associated with high O2 (85%) exposure. The mean survival time in SDRs was more than 147% that of SD rats with 168h O2 exposure. These results suggest that the enhanced resistance to oxidative stress of SDRs associated with enhanced hydrogen peroxide elimination may support its potential role in lifespan extension.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalExperimental Gerontology
Volume48
Issue number5
DOIs
Publication statusPublished - 2013 May

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Keywords

  • Aging
  • Dwarf
  • Growth hormone
  • Lifespan
  • Oxidative stress

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology

Cite this

Sasaki, T., Tahara, S., Shinkai, T., Kuramoto, K., Matsumoto, S., Yanabe, M., ... Kaneko, T. (2013). Lifespan extension in the spontaneous dwarf rat and enhanced resistance to hyperoxia-induced mortality. Experimental Gerontology, 48(5), 457-463. https://doi.org/10.1016/j.exger.2013.02.015