HETEROCEPHALUS GLABER
One particularly incredible organism is the naked mole-rat, Heterocephalus glaber. They are known for their remarkable longevity, with the longest lifespan recorded at 31 years. This is in stark contrast to the typical two or four years that other rodents might live. One notable adaptation of the naked mole-rat is its hypoxia tolerance.
The naked mole-rat lives in underground burrows, an environment with limited available oxygen. Consistent with these hypoxic conditions in the evolutionary lens, the naked mole-rat has adapted to resist hypoxia-induced oxidative damage (Hadj-Moussa et al., 2022). In other words, given the hypoxic conditions of the underground environment, mutations that emphasized anaerobic respiration and oxidative stress resistance were advantageous for the survival and longevity of the naked mole-rat. One specific mechanism that enables such hypoxia resistance is the naked mole-rat’s ability to reduce its metabolic rate under hypoxic conditions. In this metabolic rate depression, the initial hypoxia conditions are detected via sensors such as hypoxia-inducible factors, HIFs. This detection leads to the slowing of energy usage and mitochondrial function. This slowing of mitochondrial function triggers anaerobic respiration, such as glycolysis and fructose metabolism. Rather than oxidative phosphorylation, the naked mole-rat can increase glycolysis. The naked mole-rat also has an ample supply of heat shock proteins, which help mitigate oxidative stress. Another manner in which the naked mole-rat is resilient under low oxygen conditions is through its ability to switch from metabolizing glucose to metabolizing fructose.
One way in which this research is significant for the future of modern medicine is through its application to better understand ischemia-reperfusion injuries. A reperfusion, or a reoxygenation injury, is tissue damage as a direct result of blood flow returning to the tissue after a period of ischemia. Research conducted by Kadamani suggests that the brain of the naked mole-rat has an in vitro tolerance to ischemia as compared to mice (Kadamani et al., 2024). Specifically, this research underscores the medical potential of a drug mirroring the naked mole-rat’s antioxidant mechanisms, limiting the buildup of reactive oxygen species, ROS (Kadamani et al., 2024).
REFERENCES:
Hadj-Moussa, H., Eaton, L., Cheng, H., Pamenter, M. E., & Storey, K. B. (2022). Naked mole-rats resist the accumulation of hypoxia-induced oxidative damage. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 273, 111282. https://doi.org/10.1016/j.cbpa.2022.111282
Kadamani, K. L., Rahnamaie-Tajadod, R., Eaton, L., Bengtsson, J., Ojaghi, M., Cheng, H., & Pamenter, M. E. (2024). What can naked mole-rats teach us about ameliorating hypoxia-related human diseases? Annals of the New York Academy of Sciences. https://doi.org/10.1111/nyas.15219