Stereological analysis of the naked mole-rat <i>Heterocephalus glaber</i> lung provides evidence of altered surfactant function and late alveolarization

Naked-mole rats (NMRs; <i>Heterocephalus glaber</i>) exhibit unique biological traits such as resistance to cancer, exceptional longevity, and high tolerance to low-oxygen environments. However, little is known about the lung structure of this eusocial species. Here, the lungs of adult NMRs were qualitatively examined using light and electron microscopy, followed by structural quantification of the alveolar region by means of stereology. One queen (>18 years) was also included in the study. The data normalized to body weight (BW) were furthermore compared to that of young and old mice (<i>Mus musculus</i>) as well as the expression of genes of surfactant proteins. Qualitatively, NMRs showed larger conducting airways compared to mice. Additionally, alveolar septa with a double-layered capillary network were observed in NMRs, indicating microvascular maturation and late alveolarization. Stereological analysis of the lung parenchyma revealed a lower septal surface area and alveolar epithelial type II (AEII) cell number per BW in NMRs compared to mice. However, in NMRs, the AEII cells were larger with a higher content of lamellar bodies, resulting in more intracellular surfactant per BW. Furthermore, the expression of surfactant protein B (<i>Sftpb</i>) was prominently higher in NMRs. The queen showed a larger mean alveolar volume, but no other age-related structural alterations were observed. The results indicate that NMRs are capable of late alveolarization, which is in line with their good regenerative potential. Additionally, NMRs have more intracellular surfactant and higher expression of <i>Sftpb</i>, suggesting functional alterations in their surfactant system possibly as an environmental adaptation.<b>NEW & NOTEWORTHY</b> Naked mole-rats (NMRs) can adapt to hypoxic environments and are the longest-living rodents. Comparison of their lung structure with that of mice revealed that NMRs have a reduced alveolar surface area per body weight but an increased pool of intracellular surfactant. Additionally, the septa of NMRs were thicker with an occasional double-layered capillary network. These features indicate a high regenerative potential with late alveolarization and environmental adaptation, even in old animals (>18 years).