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

Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H919-27. doi: 10.1152/ajpheart.01287.2006. Epub 2007 Apr 27.

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: approximately 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 (O(2)(*-)) and H(2)O(2) 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 ( approximately 250-300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a approximately 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 gp91(phox), 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.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Antioxidants / metabolism
  • Apoptosis
  • Carotid Arteries / drug effects
  • Carotid Arteries / metabolism*
  • Carotid Arteries / pathology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Hydrogen Peroxide / metabolism
  • Longevity*
  • Mole Rats / metabolism*
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology
  • Oxidative Stress*
  • Phenotype
  • Rats
  • Rats, Inbred F344
  • Reactive Oxygen Species / metabolism*
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Species Specificity
  • Superoxides / metabolism
  • Vasodilation* / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Antioxidants
  • Nitric Oxide Donors
  • Reactive Oxygen Species
  • Vasodilator Agents
  • Superoxides
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Hydrogen Peroxide
  • Acetylcholine