Table 4.

Phenotypic differences between naked mole-rats and mice

Phenotype/Pathway	Naked mole-rat vs. Mouse (C57Bl/6)
Oxidative damage	↑
Antioxidant levels	→
Cytoprotective [NRF2] signaling activity	↑
Genome maintenance (DNA repair)	↑
Cancer incidence	↓
Telomere length	↓
Telomerase	↓
Tolerance of hypoxia and hypercapnia	↑
mTOR signaling	↓
Proteome maintenance	↑
Autophagy	↑
Proteasome activity	↑

Naked mole-rats are extraordinarily long-lived compared to the similarly sized mouse. Many previous studies have started to characterize aging-related phenotypes in the naked mole-rat. Compared to shorter-lived mice (i.e., C57Bl/6), naked mole-rats are cancer resistant and tolerant of exogenous stressors including hypoxia and hypercapnia. They also have elevated proteome and genome maintenance, autophagy, and proteasome activity levels compared to mice. Strikingly, they have high levels of oxidative damage even from a young age compared to mice, and both species have similar levels of antioxidant enzymes (i.e., SOD). Despite this, naked mole-rats have high constitutive levels of cytoprotective NRF2-signaling activity. This may be one critical pathway that contributes to their lengthened healthspan and lifespan