Genome Stability Maintenance in Naked Mole-Rat

Abstract

The naked mole-rat (Heterocephalus glaber) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest living rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance. Despite the fact that the naked mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main characteristics of its genome and proteome are high stability and effective functioning. Replicative senescence in the somatic cells of naked mole-rats is missing, while an additional p53/pRb-dependent mechanism of early contact inhibition has been revealed in its fibroblasts, which controls cell proliferation and its mechanism of arf-dependent aging. The unique traits of phenotypic and molecular adaptations found in the naked mole-rat speak to a high stability and effective functioning of the molecular machinery that counteract damage accumulation in its genome. This review analyzes existing results in the study of the molecular basis of longevity and high cancer resistance in naked mole-rats. KEYWORDS Heterocephalus glaber, cancer resistance, genome and proteome stability, DNA repair. ABBREVIATIONS H. glaber -Heterocephalus glaber; Spalax -Spalax galili; M. musculus -Mus Musculus; MLSmaximum life span; OD -oxidative damages; GPX1 -glutathione peroxidase; GSH -reduced glutathione; ECIearly contact inhibition; HA -hyaluronic acid; HAS2 -hyaluronan synthase 2; PARP -poly(ADP-ribose) polymerase; PARG -poly(ADP-ribose) glycohydrolase; NMR -naked mole-rat.

Genome-Protecting Compounds as Potential Geroprotectors

“…On the other hand, an increased expression of a number of genes, providing a response to DNA damage and repair, causes an increase in the lifespan of model animals [ 2 , 11 ]. Species with extreme longevity, such as naked mole rats, Brandt bats, whales, mole rat Spalax , and parrots have adaptive features of repair mechanisms that increase the stability of their DNA [ 12 , 13 , 14 , 15 , 16 ]. In addition, reliable DNA protection is one of the reasons for the immortality of germline cells [ 17 ].…”

Hypothesis: Potentially Systemic Impacts of Elevated CO2 on the Human Proteome and Health

“…NMR inhabits underground galleries under extreme crowding and, as a consequence, is adapted to extraordinarily high pCO 2 levels in their burrows (58,59). Remarkably, the only difference found thus far between NMR and its closest rodent relatives inhabiting outdoor environments is the substantially enhanced proteome fold stability, the resistance to reactive oxygen species (60), and/thus efficient DNA repair mechanisms in their acidized blood (60,61). However, their remarkable properties vanish when NMRs are forced to live at atmospheres with ambient pCO 2 (62).…”

Imiquimod does not elicit inflammatory responses in the skin of the naked mole rat (Heterocephalus glaber)

“…NMRs resist or tolerate various potentially harmful conditions or stimuli including hypoxia [ 35 ], inflammatory pain [ 36 ], histamine-induced itch [ 37 ] and cancer [ 38 – 40 ]. Due to these traits and its extreme longevity, the animal has attracted a lot of interest in biomedical research [ 41 ]. Given its resistance and unique skin structure, the animal could be a good model to study psoriasis and other skin disorders.…”