And the Beat Goes On: Maintained Cardiovascular Function During Aging in the Longest-Lived Rodent, the Naked Mole-Rat

Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H284-91. doi: 10.1152/ajpheart.00305.2014. Epub 2014 Jun 6.

Abstract

The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans.

Keywords: arterial stiffness; cardiac reserve; cardiovascular aging; naked mole-rat; negligible senescence.

Publication types

  • Comparative Study
  • 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

  • Age Factors
  • Aging / metabolism
  • Aging / physiology*
  • Animals
  • Aorta / physiology*
  • Arterial Pressure
  • Collagen / metabolism
  • Compliance
  • Echocardiography, Stress
  • Female
  • Heart / physiology*
  • Heart Rate*
  • Longevity
  • Male
  • Mole Rats / metabolism
  • Mole Rats / physiology*
  • Myocardium / metabolism
  • Pulse Wave Analysis
  • Time Factors
  • Vascular Stiffness
  • Ventricular Function, Left*

Substances

  • Collagen