Delayed Onset of Age-Dependent Changes in Ultrastructure of Myocardial Mitochondria as One of the Neotenic Features in Naked Mole Rats (Heterocephalus glaber)

Abstract

In this study, the ultrastructure of mitochondria in cardiomyocytes of naked mole rats (Heterocephalus glaber) aged from 6 months to 11 years was examined. Mitochondria in cardiomyocytes of naked mole rats have a specific ultrastructure that is different from those in cardiomyocytes of other mammalian species studied to date. In contrast to mitochondria of other mammalian cardiomyocytes, where the internal space is completely filled by tightly packed parallel rows of cristae, mitochondria in cardiomyocytes of naked mole rats have a chaotic pattern of cristae organization with wave-like contours. Gradual formation of mitochondrial ultrastructure occurs in naked mole rats for many years. Two mitochondrial populations are developed to the age of 5 years. In addition to the main population, there are some large organelles which exceed normal sizes by two to three times. Most cristae in these mitochondria are assembled into small groups, which form the curved and ring-like structures. The appearance of some specific structural changes (i.e. bundles of parallel cristae) is observed in the mitochondrial population of naked mole rat after 11 years of age. However, these bundles are very rare and of sporadic nature. Morphometric analysis has shown that the superficial density of the inner mitochondrial membrane is similar in all examined age groups of naked mole rats: 21.1 at 6 months; 23.21 at 3 years; 23.55 at 5 years; and 20.8 at 11 years. This level is almost two times lower than in other animals studied (mice and rats). The data demonstrate that pathological changes in mitochondrial apparatus are not present in naked mole rats at least until the age of 11 years. The mitochondrial apparatus corresponds to the phenotype in young animals, thus being another neotenic feature in naked mole rats.

Phylogenetic modeling of enhancer shifts in African mole-rats reveals regulatory changes associated with tissue-specific traits

“…Several studies have documented alterations in mitochondrial function [16,42] and morphology [58,59] in mole-rats, which our results support from an epigenomic perspective. Moreover, we found lineage-specific liver enhancers in mole-rats enrich for SINE repeat families and associate with fatty acid oxidation processes, which is in agreement with the reported increase in fatty acid utilization in mole-rat liver [16].…”

Lipid membranes from naked mole-rat brain lipids are cholesterol-rich, highly phase-separated, and sensitive to amyloid-induced damage

“…The naked mole-rat is a long-lived species having a life span that can exceed 30 years 1,2 , which is nearly ten times longer than that of rodents of comparable size. Possessing many neotenic features 3,4 and defying many of the signs of ageing 5 , the naked mole-rat does not appear to develop neurodegenerative disease 6,7 .…”

Progressive reorganization of mitochondrial apparatus in aging skeletal muscle of naked mole rats (Heterocephalus glaber) as revealed by electron microscopy: potential role in continual maintenance of muscle activity

“…The whole intermembrane space of the mitochondrion is filled with cristae in the form of curled, wave-like structures (indicated by arrows). It should be noted that previously we found mitochondria of similar ultrastructure in cardiomyocytes of naked mole rat aged above 5 years [ 34 ].…”

“…The available literature lacks data on the ultrastructural study of naked mole rat tissues except for the study by Onyango et al [ 32 ] performed using the testis of naked mole rat, and the work of Stoll et al [ 33 ] in which selected electron microscopic images are provided for illustration of histological and functional characteristics of naked mole rat. Our investigations [ 34 ] of the mitochondrial ultrastructure of cardiomyocytes of naked mole rat demonstrated that by the age of 11 years their mitochondria do not show any abnormalities. The mitochondrial ultrastructure corresponds to the phenotype of young animal which is one of the neotenic features in naked mole rat.…”