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 language | English |
|---|---|
| Pages (from-to) | 463-471 |
| Number of pages | 9 |
| Journal | Aging Cell |
| Volume | 5 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2006 |
| Externally published | Yes |
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Keywords
- DNA damage
- Glutathione
- Longevity
- Maximum lifespan
- Naked mole-rats
- Oxidative stress
ASJC Scopus subject areas
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - High oxidative damage levels in the longest-living rodent, the naked mole-rat
AU - Andziak, Blazej
AU - O'Connor, Timothy P.
AU - Qi, Wenbo
AU - Dewaal, Eric M.
AU - Pierce, Anson
AU - Chaudhuri, Asish R.
AU - Van Remmen, Holly
AU - Buffenstein, Rochelle
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - DNA damage
KW - Glutathione
KW - Longevity
KW - Maximum lifespan
KW - Naked mole-rats
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=33751242066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751242066&partnerID=8YFLogxK
U2 - 10.1111/j.1474-9726.2006.00237.x
DO - 10.1111/j.1474-9726.2006.00237.x
M3 - Article
C2 - 17054663
AN - SCOPUS:33751242066
VL - 5
SP - 463
EP - 471
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 6
ER -