Insights into the Molecular Basis of Genome Stability and Pristine Proteostasis in Naked Mole-Rats

The naked mole-rat (Heterocephalus glaber) is the longest-lived rodent, with a maximal reported lifespan of 37 years. In addition to its long lifespan - which is much greater than predicted based on its small body size (longevity quotient of ~4.2) - naked mole-rats are also remarkably healthy well into old age. This is reflected in a striking resistance to tumorigenesis and minimal declines in cardiovascular, neurological and reproductive function in older animals. Over the past two decades, researchers have been investigating the molecular mechanisms regulating the extended life- and health- span of this animal, and since the sequencing and assembly of the naked mole-rat genome in 2011, progress has been rapid. Here, we summarize findings from published studies exploring the unique molecular biology of the naked mole-rat, with a focus on mechanisms and pathways contributing to genome stability and maintenance of proteostasis during aging. We also present new data from our laboratory relevant to the topic and discuss our findings in the context of the published literature.