Thioredoxin 1 overexpression extends mainly the earlier part of life span in mice

J Gerontol A Biol Sci Med Sci. 2011 Dec;66(12):1286-99. doi: 10.1093/gerona/glr125. Epub 2011 Aug 26.

Abstract

We examined the effects of increased levels of thioredoxin 1 (Trx1) on resistance to oxidative stress and aging in transgenic mice overexpressing Trx1 [Tg(TRX1)(+/0)]. The Tg(TRX1)(+/0) mice showed significantly higher Trx1 protein levels in all the tissues examined compared with the wild-type littermates. Oxidative damage to proteins and levels of lipid peroxidation were significantly lower in the livers of Tg(TRX1)(+/0) mice compared with wild-type littermates. The survival study demonstrated that male Tg(TRX1)(+/0) mice significantly extended the earlier part of life span compared with wild-type littermates, but no significant life extension was observed in females. Neither male nor female Tg(TRX1)(+/0) mice showed changes in maximum life span. Our findings suggested that the increased levels of Trx1 in the Tg(TRX1)(+/0) mice were correlated to increased resistance to oxidative stress, which could be beneficial in the earlier part of life span but not the maximum life span in the C57BL/6 mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aging / genetics
  • Aging / pathology
  • Aging / physiology
  • Animals
  • Antioxidants / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Diquat / toxicity
  • Female
  • Glutaredoxins / metabolism
  • Glutathione / metabolism
  • Lipid Peroxidation
  • Liver / metabolism
  • Longevity / genetics*
  • Longevity / physiology*
  • MAP Kinase Kinase Kinase 5 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • NF-kappa B / genetics
  • Oxidation-Reduction
  • Oxidative Stress
  • Sex Characteristics
  • Thioredoxins / genetics*
  • Thioredoxins / metabolism
  • Thioredoxins / physiology*
  • Up-Regulation

Substances

  • Antioxidants
  • Glrx protein, mouse
  • Glutaredoxins
  • NF-kappa B
  • Txn1 protein, mouse
  • Txn2 protein, mouse
  • Thioredoxins
  • 8-Hydroxy-2'-Deoxyguanosine
  • Diquat
  • MAP Kinase Kinase Kinase 5
  • Map3k5 protein, mouse
  • Deoxyguanosine
  • Glutathione