Fight Aging!

Naked mole rats exhibit negligible senescence, meaning that that individuals show a minimal functional decline as a result of aging until very late life. They exhibit a very low incidence of cancer. They are one of the most studied species in the context of the comparative biology of aging, the search for longevity assurance mechanisms in unusually long-lived species that might become the basis for therapies to treat aging in humans. That naked mole rats are mammals gives the hope that any discoveries are more likely to be relevant to our species than is the case for investigations of lower animals, such as the work on exceptional regeneration in salamanders or zebrafish.

In today's open access paper, the authors discuss heart function in aging naked mole rats. There is little speculation on mechanisms; the researchers involved only measured heart function. As is the case for most biological systems in the naked mole rat, an old heart performs about as well as a young heart. We know from other research that the harmful accumulation of senescent cells with age contributes to cardiac fibrosis and hypertrophy in mammals, while senescent cell behavior is unusually innocuous in naked mole rats. Other relevant issues that are less well investigated in the naked mole rat include calcification of cardiac tissue (where senescent cells also play a role, it seems) and stiffening of arteries due to cross-linking and other causes. It remains to be seen as to what can be learned from all of this.

Naked mole-rats maintain cardiac function and body composition well into their fourth decade of life

The prevalence of cardiovascular disease increases exponentially with age, highlighting the contribution of aging mechanisms to cardiac diseases. Although model organisms which share human disease pathologies can elucidate mechanisms driving disease, they do not provide us with innate examples how cardiac aging might be slowed or attenuated. The identification of animal models that preserve cardiac function throughout most of life offers an alternative approach to study mechanisms which might slow cardiac aging. One such species may be the naked mole-rat (NMR), a mouse-sized (40 g) rodent with extraordinary longevity (more than 37 years), and constant mortality hazard over its four decades of life.

We used a cross-sectional study design to measure a range of physiological parameters in NMRs between 2 and 34 years of age and compared these findings with those of mice aged between 3 months and 2.5 years. We observed a rapid decline in body fat content and bone mineral density in old mice, but no changes in NMRs. Similarly, rhythm disorders (premature atrial and ventricular complexes) occurred in aged mice but not in NMRs. Magnetic resonance and ultrasound imaging showed age-dependent increases in cardiac hypertrophy and diastolic dysfunction in mice which were absent in NMRs. Finally, cardiac stress tests showed an age-dependent decline in normalized cardiac output in mice, which was absent in NMRs.

This study demonstrates that unlike mice that exhibit pronounced declines in body composition and cardiac function commencing shortly after sexual maturity, NMRs can maintain tissue homeostasis throughout their four-decade long maximum lifespan. Furthermore, NMRs do not show any signs of diastolic dysfunction or cardiac hypertrophy and maintain similar functional cardiac reserve capacity at advanced age to that exhibited when young adults, at the prime of life. Collectively, these data reveal that the naked mole-rat provides a proof-of-concept that age-related declines in body composition and cardiac function are not inevitable. Elucidating these mechanisms may lead to the discovery of therapies to reduce the burden of age-associated cardiovascular pathology, morbidity, and mortality and thereby enhance quality of life in older humans.