Abstract 9857: Cardiac Function in an Extraordinarily Long-lived Rodent, the Naked Mole-rat

Abstract

Mechanisms underlying prolonged maintenance of cardiac function in long-lived species may differ from those involved in short-lived species. We assessed cardiac function in young (2-4 year old) male and female naked mole-rats (NMRs; Heterocephalus glaber) and compared these data to those of young (7-8 month old) male and female C57BL/6 mice to establish the use of the NMR for cardiac aging studies. NMRs have a maximum lifespan potential of 32 years (8-fold longer than mice) despite being comparably sized. Furthermore, NMRs maintain good health for at least 75% of their extremely long lifespan, equivalent to >80 year old humans. As such, NMRs provide us a unique opportunity to explore mechanisms that enable prolonged maintenance of cardiac function. Like humans NMRs have a lower than predicted heart rate for their body size. Interestingly, unlike in mice, isofluorane anesthesia had little depressive effect on NMR cardiac function, as heart rates stayed similar between anesthetized and unanesthetized NMRs. Echocardiography revealed significant differences between species (see table). While there were no species differences in average diastolic wall thickness, average systolic wall thickness was greater in mice compared to NMRs. Baseline fractional shortening (FS) was significantly lower in NMRs than in mice. Dobutamine stress echocardiography (3 μg/g body weight i.p.) elicited a greater increase in FS in NMRs than in mice, suggesting that NMRs have greater cardiac reserve. Doppler analysis of blood flow revealed that diastolic (E/A ratio) and systolic (aortic peak velocity) function were significantly different between species. The higher NMR E/A ratio is indicative of more pliable ventricle muscle and less reliance on atrial filling. The interspecies differences observed may indicate mechanisms employed by NMRs to prolong cardiac health into old age. Future studies will probe the existence of such mechanisms and investigate age-related cardiac changes in NMRs.