Vascular aging in the longest-living rodent, the naked mole rat

Anna Csiszar, Nazar Labinskyy, Zsuzsanna Orosz, Zhao Xiangmin, Rochelle Buffenstein, Zoltan Ungvari

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Abstract

The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known [maximum lifespan potential (MLSP): >28 yr] and is a unique model of successful aging showing attenuated declines in most physiological function. This study addresses age-related changes in endothelial function and production of reactive oxygen species in NMR arteries and vessels of shorter-living Fischer 344 rats (MLSP: ∼3 yr). Rats exhibit a significant age-dependent decline in acetylcholine-induced responses in carotid arteries over a 2-yr age range. In contrast, over a 10-yr age range nitric oxide (NO)-mediated relaxation responses to acetylcholine and to the NO donor S-nitrosopencillamine (SNAP) were unaltered in NMRs. Cellular superoxide anion (O2•-) and H2O2 production significantly increased with age in rat arteries, whereas they did not change substantially with age in NMR vessels. Indicators of apoptotic cell death (DNA fragmentation rate, caspase 3/7 activity) were significantly enhanced (∼250-300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a ∼50% increase in apoptotic cell death. In the hearts of NMRs (2 to 26 yr old), expression of endothelial NO synthase, antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, catalase, and glutathione peroxidase), the NAD(P)H oxidase subunit gp91phox, and mitochondrial proteins (COX-IV, ATP synthase, and porin, an indicator of mitochondrial mass) did not change significantly with age. Thus long-living NMRs can maintain a youthful vascular function and cellular oxidant-antioxidant phenotype relatively longer and are better protected against aging-induced oxidative stress than shorter-living rats.

Original languageEnglish (US)
Pages (from-to)H919-H927
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number2
DOIs
Publication statusPublished - Aug 1 2007

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Keywords

  • Atherosclerosis
  • Comparative biology
  • Oxidative stress
  • Senescence
  • Vascular disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Csiszar, A., Labinskyy, N., Orosz, Z., Xiangmin, Z., Buffenstein, R., & Ungvari, Z. (2007). Vascular aging in the longest-living rodent, the naked mole rat. American Journal of Physiology - Heart and Circulatory Physiology, 293(2), H919-H927. https://doi.org/10.1152/ajpheart.01287.2006