Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun 2;22(11):6011.
doi: 10.3390/ijms22116011.

DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat

Harvey Boughey  1 , Mateusz Jurga  2 , Sherif F El-Khamisy  1   2
Affiliations
Review

DNA Homeostasis and Senescence: Lessons from the Naked Mole Rat

Harvey Boughey et al. Int J Mol Sci. .

Abstract

As we age, our bodies accrue damage in the form of DNA mutations. These mutations lead to the generation of sub-optimal proteins, resulting in inadequate cellular homeostasis and senescence. The build-up of senescent cells negatively affects the local cellular micro-environment and drives ageing associated disease, including neurodegeneration. Therefore, limiting the accumulation of DNA damage is essential for healthy neuronal populations. The naked mole rats (NMR) are from eastern Africa and can live for over three decades in chronically hypoxic environments. Despite their long lifespan, NMRs show little to no biological decline, neurodegeneration, or senescence. Here, we discuss molecular pathways and adaptations that NMRs employ to maintain genome integrity and combat the physiological and pathological decline in organismal function.

Keywords: DNA damage; DNA repair; ageing; naked mole rat; neurodegeneration; oxidative stress; reactive oxygen species; senescence.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Summary of features relevant to neurodegeneration among mice, humans and naked mole rats. While mice and human cells are sensitive to hypoxia and lose zinc homeostasis with age, human and NMR cells share upregulated DNA damage response (DDR), including highly expressed mismatch repair, non-homologous end-joining, homology-directed repair and base excision repair pathways. Moreover, both NMRs and humans share a high lifespan to body ratio and express a unique subunit of the RPA complex—RPA4.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Smith E.S.J., Schuhmacher L.-N., Husson Z. The naked mole-rat as an animal model in biomedical research: Current perspectives. Open Access Anim. Physiol. 2015;7:137. doi: 10.2147/OAAP.S50376. - DOI
    1. Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D., et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018;13:757–772. doi: 10.2147/CIA.S158513. - DOI - PMC - PubMed
    1. Gorbunova V., Seluanov A., Zhang Z., Gladyshev V.N., Vijg J. Comparative genetics of longevity and cancer: Insights from long-lived rodents. Nat. Rev. Genet. 2014;15:531–540. doi: 10.1038/nrg3728. - DOI - PMC - PubMed
    1. Martínez-Cué C., Rueda N. Cellular Senescence in Neurodegenerative Diseases. Front. Cell. Neurosci. 2020;14:16. doi: 10.3389/fncel.2020.00016. - DOI - PMC - PubMed
    1. Buffenstein R. The Naked Mole-Rat: A New Long-Living Model for Human Aging Research. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2005;60:1369–1377. doi: 10.1093/gerona/60.11.1369. - DOI - PubMed