High oxidative damage levels in the longest-living rodent, the naked mole-rat

Blazej Andziak, Timothy P. O'Connor, Wenbo Qi, Eric M. Dewaal, Anson Pierce, Asish R. Chaudhuri, Holly Van Remmen, Rochelle Buffenstein

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

Oxidative stress is reputed to be a significant contributor to the aging process and a key factor affecting species longevity. The tremendous natural variation in maximum species lifespan may be due to interspecific differences in reactive oxygen species generation, antioxidant defenses and/or levels of accrued oxidative damage to cellular macromolecules (such as DNA, lipids and proteins). The present study tests if the exceptional longevity of the longest living (> 28.3 years) rodent species known, the naked mole-rat (NMR, Heterocephalus glaber), is associated with attenuated levels of oxidative stress. We compare antioxidant defenses (reduced glutathione, GSH), redox status (GSH/GSSG), as well as lipid (malondialdehyde and isoprostanes), DNA (8-OHdG), and protein (carbonyls) oxidation levels in urine and various tissues from both mole-rats and similar-sized mice. Significantly lower GSH and GSH/GSSG in mole-rats indicate poorer antioxidant capacity and a surprisingly more pro-oxidative cellular environment, manifested by 10-fold higher levels of in vivo lipid peroxidation. Furthermore, mole-rats exhibit greater levels of accrued oxidative damage to lipids (twofold), DNA (∼two to eight times) and proteins (1.5 to 2-fold) than physiologically age-matched mice, and equal to that of same-aged mice. Given that NMRs live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress explain the impressive longevity of this species.

Original languageEnglish
Pages (from-to)463-471
Number of pages9
JournalAging Cell
Volume5
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

Fingerprint

Mole Rats
Rodentia
8-epi-prostaglandin F2alpha
Oxidative Stress
Glutathione Disulfide
Antioxidants
Lipids
DNA
Proteins
Body Size
Malondialdehyde
Lipid Peroxidation
Oxidation-Reduction
Glutathione
Reactive Oxygen Species
Urine

Keywords

  • DNA damage
  • Glutathione
  • Longevity
  • Maximum lifespan
  • Naked mole-rats
  • Oxidative stress

ASJC Scopus subject areas

  • Cell Biology

Cite this

Andziak, B., O'Connor, T. P., Qi, W., Dewaal, E. M., Pierce, A., Chaudhuri, A. R., ... Buffenstein, R. (2006). High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell, 5(6), 463-471. https://doi.org/10.1111/j.1474-9726.2006.00237.x

High oxidative damage levels in the longest-living rodent, the naked mole-rat. / Andziak, Blazej; O'Connor, Timothy P.; Qi, Wenbo; Dewaal, Eric M.; Pierce, Anson; Chaudhuri, Asish R.; Van Remmen, Holly; Buffenstein, Rochelle.

In: Aging Cell, Vol. 5, No. 6, 12.2006, p. 463-471.

Research output: Contribution to journalArticle

Andziak, B, O'Connor, TP, Qi, W, Dewaal, EM, Pierce, A, Chaudhuri, AR, Van Remmen, H & Buffenstein, R 2006, 'High oxidative damage levels in the longest-living rodent, the naked mole-rat', Aging Cell, vol. 5, no. 6, pp. 463-471. https://doi.org/10.1111/j.1474-9726.2006.00237.x
Andziak B, O'Connor TP, Qi W, Dewaal EM, Pierce A, Chaudhuri AR et al. High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell. 2006 Dec;5(6):463-471. https://doi.org/10.1111/j.1474-9726.2006.00237.x
Andziak, Blazej ; O'Connor, Timothy P. ; Qi, Wenbo ; Dewaal, Eric M. ; Pierce, Anson ; Chaudhuri, Asish R. ; Van Remmen, Holly ; Buffenstein, Rochelle. / High oxidative damage levels in the longest-living rodent, the naked mole-rat. In: Aging Cell. 2006 ; Vol. 5, No. 6. pp. 463-471.
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