Advertisement

Biochemistry (Moscow)

, Volume 82, Issue 12, pp 1504–1512 | Cite as

Spontaneous and experimentally induced pathologies in the naked mole rat (Heterocephalus glaber)

  • V. N. ManskikhEmail author
  • O. A. Averina
  • A. I. Nikiforova
Review

Abstract

The naked mole rat (Heterocephalus glaber, Rüppell, 1842) is a unique eusocial rodent with unusually long lifespan. Therefore, the study of spontaneous and experimentally induced pathologies in these animals is one of the most important tasks of gerontology. Various infections, noninfectious pathologies (including age-dependent changes), and tumors have been described in the naked mole rat. The most frequent pathologies are traumas (bite wounds), purulent and septic complications of traumatic injuries, renal tubular calcinosis, chronic progressive nephropathy, hepatic hemosiderosis, testicular interstitial cell hyperplasia, calcinosis cutis, cardiomyopathy, and dysbiosis-related infectious lesions of the digestive system. However, the summarized data on pathology (including tumor incidence) and on the causes of mortality are insufficient. There are only few publications about the results of experiments where pathologies were induced in the naked mole rat. All these problems could be subjects for promising future studies without which adequate studies on mechanisms providing the long lifespan of the naked mole rat are impossible, as well as the elucidation of causes of tumor resistance of this species.

Keywords

aging and age-related diseases naked mole rat resistance of animals to tumors spontaneous pathologies laboratory animals 

Abbreviations

CPN

chronic progressive nephropathy

hTERT

human telomerase reverse transcriptase

ras

(rat sarcoma) oncogene

SV40 TAg

simian virus 40 tumor antigen

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Buffenstein, R. (2005) The naked mole-rat: a new long-living model for human aging research, J. Gerontol. A. Biol. Sci. Med. Sci., 60, 1369–1377.CrossRefPubMedGoogle Scholar
  2. 2.
    Buffenstein, R. (2008) Negligible senescence in the longest living rodent, the naked mole rat: insights from a successfully aging species, J. Comp. Physiol., 178, 439–445.Google Scholar
  3. 3.
    Edrey, Y. H., Hanes, M., Pinto, M., Mele, J., and Buffenstein, R. (2011) Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research, ILAR J., 52, 41–53.CrossRefPubMedGoogle Scholar
  4. 4.
    Buffenstein, R., Park, T., Hanes, M., and Artwohl, J. E. (2012) The naked mole rat, in The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents, Ser. American College of Laboratory Animal Medicine, Elsevier, Academic Press, pp. 1055–1074.CrossRefGoogle Scholar
  5. 5.
    Skulachev, V. P. (2015) Moscow news: two more representatives of sodium motive force generators (Na+-cbb3 oxi-dase and Na+-bacteriorhodopsin); natural delay of the aging program (neoteny) in mammals, namely in the naked mole rat and “naked ape” (human): Abst. 11th Conf. Physiology of Mitochondria (MiP2015), Lucni Bouda, Czech Republic, pp. 64–66.Google Scholar
  6. 6.
    Penz, O. K., Fuzik, J., Kurek, A. B., Romanov, R., Larson, J., Park, T. J., Harkany, T., and Keimpema, E. (2015) Protracted brain development in a rodent model of extreme longevity, Sci. Rep., 5, 11592.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Skulachev, V. P. (2016) The naked mole rats and humans: highly social creatures prolonging youth by delay of ontogenesis (neoteny): Abst. 3rd Conf. Biomedical Innovations for Healthy Longevity, Aging (Albany, NY), 9, 6–7.Google Scholar
  8. 8.
    Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakeeva, L. E., Skulachev, M. V., Markov, A. V., Hildebrandt, T. B., and Sadovnichii, V. A. (2017) Neoteny, prolongation of youth: from the naked mole rats to “naked apes” (humans), Physiol. Rev., 97, 699–720.PubMedGoogle Scholar
  9. 9.
    Artwohl, J., Ball-Kell, S., Valyi-Nagy, T., Wilson, S. P., Lu, Y., and Park, T. J. (2009) Extreme susceptibility of African the naked mole rats (Heterocephalus glaber) to experimental infection with herpes simplex virus type 1, Comp. Med., 59, 83–90.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Githure, J. I., Gardener, P. J., and Kinoti, G. K. (1988) Experimental infection of the naked mole-rat, Heterocephalus glaber, with Leishmania donovani, Trans. R. Soc. Trop. Med. Hyg., 82,563.CrossRefPubMedGoogle Scholar
  11. 11.
    Hill, W. C. O., Porter, A., Bloom, R. T., Seago, J., and Southwick, M. D. (1957) Field and laboratory studies on the naked mole rat, Heterocephalus glaber, J. Zool., 128, 455–514.Google Scholar
  12. 12.
    Manskikh, V. N. (2014) Aging and respiratory infections in laboratory animals, Usp. Geronotol., 27, 425–431.Google Scholar
  13. 13.
    Delaney, M. A., Nagy, L., Kinsel, M. J., and Treuting, P. M. (2013) Spontaneous histologic lesions of the adult the naked mole rat (Heterocephalus glaber): a retrospective survey of lesions in a zoo population, Vet. Pathol., 50, 607–621.CrossRefPubMedGoogle Scholar
  14. 14.
    Ross-Gillespie, A., O’Riain, M. J., and Keller, L. F. (2007) Viral epizootic reveals inbreeding depression in a habitually inbreeding mammal, Evolution, 61, 2268–2273.CrossRefPubMedGoogle Scholar
  15. 15.
    Taylor, K. R., Milone, N. A., and Rodriguez, C. E. (2017) Four cases of spontaneous neoplasia in the naked mole-rat (Heterocephalus glaber), a putative cancer-resistant species, J. Gerontol. A Biol. Sci. Med. Sci., 72, 38–43.CrossRefPubMedGoogle Scholar
  16. 16.
    Lagunas-Rangel, F. A., and Chavez-Valencia, V. (2017) Learning of nature: the curious case of the naked mole rat, Mech. Ageing Dev., 164, 76–81.CrossRefPubMedGoogle Scholar
  17. 17.
    Gorbunova, V., Seluanov, A., Zhang, Z., Gladyshev, V. N., and Vijg, J. (2014) Comparative genetics of longevity and cancer: insights from long-lived rodents, Nat. Rev. Genet., 15, 531–540.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Anisimov, V. N. (2007) Biology of aging and cancer, Cancer Control, 14, 23–31.CrossRefPubMedGoogle Scholar
  19. 19.
    Delaney, M. A., Ward, J. M., Walsh, T. F., Chinnadurai, S. K., Kerns, K., Kinsel, M. J., and Treuting, P. M. (2016) Initial case reports of cancer in naked mole-rats (Heterocephalus glaber), Vet. Pathol., 53, 691–696.CrossRefPubMedGoogle Scholar
  20. 20.
    Tucker, M. J. (1997) Diseases of the Wistar Rat, Taylor and Francis, London.Google Scholar
  21. 21.
    Maronpot, R. R. (1999) Pathology of the Mouse, Cache River Press, Vienna, IL.Google Scholar
  22. 22.
    Percy, D. H., Griffey, S. M., and Barthold, S. W. (2016) Pathology of Laboratory Rodents and Rabbits, Wiley-Blackwell.Google Scholar
  23. 23.
    Mohr, U. (1996) Pathobiology of Aging Mouse, Vols. 1/2, ILSI Press.Google Scholar
  24. 24.
    Chrisp, C. E., Turke, P., Luciano, A., Swalwell, S., Peterson, J., and Miller, R. A. (1996) Lifespan and lesions in genetically heterogenous (four-way cross) mice: a new model for aging research, Vet. Pathol., 33, 735–743.CrossRefPubMedGoogle Scholar
  25. 25.
    Lipman, R., Galecki, A., Burke, D. T., and Miller, R. A. (2004) Genetic loci that influence cause of death in a heterogeneous mouse stock, J. Gerontol. A Biol. Sci. Med. Sci., 59, 977–983.CrossRefPubMedGoogle Scholar
  26. 26.
    Manskikh, V. N., Krasilshchikova, M. S., Vygodin, V. A., and Egorov, M. V. (2014) Effect of the mitochondria-targeted antioxidant SkQ1 on development of spontaneous tumors in BALB/c mice, Biochemistry (Moscow), 79, 1136–1139.CrossRefGoogle Scholar
  27. 27.
    Siegel, R., Ma, J., Zou, Z., and Jemal, A. (2014) Cancer statistics, 2014, Cancer J. Clin., 64, 9–29.Google Scholar
  28. 28.
    Amer, M. H. (2014) Multiple neoplasms, single primaries, and patient survival, Cancer Manag. Res., 6, 119–134.Google Scholar
  29. 29.
    Coyte, A., Morrison, D. S., and McLoone, P. (2014) Second primary cancer risk–the impact of applying different definitions of multiple primaries: results from a retrospective population-based cancer registry study, BMC Cancer, 14,272.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gardner, M. B., Henderson, B. E., Rongey, R. W., Estes, J. D., and Huebner, R. J. (1973) Spontaneous tumors of aging wild house mice. Incidence, pathology, and C-type virus expression, J. Natl. Cancer Inst., 50, 719–734.CrossRefPubMedGoogle Scholar
  31. 31.
    Manskikh, V. N. (2004) Essays on Evolutionary Oncology [in Russian], Izdatelstvo SibGMU, Tomsk.Google Scholar
  32. 32.
    Shabad, L. M. (1970) Methods for Determination and Study of Blastomogenicity of Chemical Substances [in Russian], Meditsina, Moscow.Google Scholar
  33. 33.
    Manskikh, V. N., Gancharova, O. S., Novikov, E. A., Kondratyuk, E. Y., Skulachev, V. P., and Moshkin, M. P. (2015) Spectrum of spontaneous pathological changes in the Northern mole vole and influence of the mitochondriatargeted antioxidant SkQ1 on it, Usp. Gerontol., 28, 53–61.Google Scholar
  34. 34.
    Davydovsky, I. V. (1940) Analysis of the sectional material of pathoanatomical departments of hospitals, institutes and maternity hospitals for 1928-1932, Arch. Pat. Anat. Pat. Fiziol., 3, 3–66.Google Scholar
  35. 35.
    Davydovsky, I. V. (1969) General Pathology of Human [in Russian], Meditsina, Moscow.Google Scholar
  36. 36.
    Manskikh, V. N. (2010) Resistance of Guinea pigs to tumor growth: the reality of the phenomenon and its possible causes, Vopr. Onkol., 56, 514–520.PubMedGoogle Scholar
  37. 37.
    Seluanov, A., Chen, Z., Hine, C., Sasahara, T. H., Ribeiro, A. A., Catania, K. C., Presgraves, D. C., and Gorbunova, V. (2007) Telomerase activity coevolves with body mass not lifespan, Aging Cell, 6, 45–52.CrossRefPubMedGoogle Scholar
  38. 38.
    Gorbunova, V., and Seluanov, A. (2009) Coevolution of telomerase activity and body mass in mammals: from mice to beavers, Mech. Ageing Dev., 130, 3–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Miyawaki, S., Kawamura, Y., Oiwa, Y., Shimizu, A., Hachiya, T., Bono, H., Koya, I., Okada, Y., Kimura, T., Tsuchiya, Y., Suzuki, S., Onishi, N., Kuzumaki, N., Matsuzaki, Y., Narita, M., Ikeda, E., Okanoya, K., Seino, K., Saya, H., Okano, H., and Miura, K. (2016) Tumour resistance in induced pluripotent stem cells derived from naked mole-rats, Nat. Commun., 7, 11471.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Robbins, S. L., Kumar, V., and Cotran, R. S. (2010) Robbins and Cotran Pathologic Basis of Disease, 8th Edn., Saunders/Elsevier, Philadelphia.Google Scholar
  41. 41.
    Liang, S., Mele, J., Wu, Y., Buffenstein, R., and Hornsby, P. J. (2010) Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber), Aging Cell, 9, 626–635.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Seluanov, A., Hine, C., Azpurua, J., Feigenson, M., Bozzella, M., Mao, Z., Catania, K. C., and Gorbunova, V. (2009) Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat, Proc. Natl. Acad. Sci. USA, 106, 19352–19357.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Tian, X., Azpurua, J., Hine, C., Vaidya, A., Myakishev-Rempel, M., Ablaeva, J., Mao, Z., Nevo, E., Gorbunova, V., and Seluanov, A. (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat, Nature, 499, 346–349.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Pettan-Brewer, C., and Treuting, P. M. (2011) Practical pathology of aging mice, Pathobiol. Aging Age Relat. Dis., 1, 7202.CrossRefGoogle Scholar
  45. 45.
    Manskikh, V. N. (2015) Chronic progressive nephropathy in rodents as a disease caused by an expanding somatic mutant clone, Biochemistry (Moscow), 80, 582–585.CrossRefGoogle Scholar
  46. 46.
    Delaney, M. A., Kinsel, M. J., and Treuting, P. M. (2016) Renal pathology in a nontraditional aging model: the naked mole-rat (Heterocephalus glaber), Vet. Pathol., 53, 493–503.CrossRefPubMedGoogle Scholar
  47. 47.
    Fawcett, D. W., Neaves, W. B., and Flores, M. N. (1973) Comparative observations on intertubular lymphatics and the organization of the interstitial tissue of the mammalian testis, Biol. Reprod., 9, 500–532.CrossRefPubMedGoogle Scholar
  48. 48.
    Manskikh, V. N., Gancharova, O. S., Nikiforova, A. I., Krasilshchikova, M. S., Shabalina, I. G., Egorov, M. V., Karger, E. M., Milanovsky, G. E., Galkin, I. I., Skulachev, V. P., and Zinovkin, R. A. (2015) Age-associated murine cardiac lesions are attenuated by the mitochondria-targeted antioxidant SkQ1, Histol. Histopathol., 30, 353–360.PubMedGoogle Scholar
  49. 49.
    Csiszar, A., Labinskyy, N., Orosz, Z., Xiangmin, Z., and Buffenstein, R. (2007) Vascular aging in the longest-living rodent, the naked mole rat, Am. J. Physiol. Heart Circ. Physiol., 293, H919–H927.CrossRefPubMedGoogle Scholar
  50. 50.
    Park, T. J., Reznick, J., Peterson, B. L., Blass, G., Omerbasic, D., Bennett, N. C., Kuich, P. H. J. L., Zasada, C., Browe, B. M., Hamann, W., Applegate, D. T., Radke, M. H., Kosten, T., Lutermann, H., Gavaghan, V., Eigenbrod, O., Begay, V., Amoroso, V. G., Govind, V., Minshall, R. D., Smith, E. S. J., Larson, J., Gotthardt, M., Kempa, S., and Lewin, G. R. (2017) Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat, Science, 356, 307–311.CrossRefPubMedGoogle Scholar
  51. 51.
    Edrey, Y. H., Medina, D. X., Gaczynska, M., Osmulski, P. A., Oddo, S., Caccamo, A., and Buffenstein, R. (2013) Amyloid beta and the longest-lived rodent: the naked molerat as a model for natural protection from Alzheimer’s disease, Neurobiol. Aging, 34, 2352–2360.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Manskikh, V. N. (2014) The problem of determination of cause of laboratory animal’s death: a critical review of definitions of “fatal” and “incidental” lesions, Biochemistry (Moscow), 79, 1075–1080.CrossRefGoogle Scholar
  53. 53.
    Snyder, J. M., Ward, J. M., and Treuting, P. M. (2016) Cause-of-death analysis in rodent aging studies, Vet. Pathol., 53, 233–243.CrossRefPubMedGoogle Scholar
  54. 54.
    Ward, J. M., Youssef, S. A., and Treuting, P. M. (2016) Why animals die: an introduction to the pathology of aging, Vet. Pathol., 53, 229–232.CrossRefPubMedGoogle Scholar
  55. 55.
    Treuting, P. M., Snyder, J. M., Ikeno, Y., Schofield, P. N., Ward, J. M., and Sundberg, J. P. (2016) The vital role of pathology in improving reproducibility and translational relevance of aging studies in rodents, Vet. Pathol., 53, 244–249.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Rose, F. L., and Harshbarger, J. C. (1977) Neoplastic and possibly related skin lesions in neotenic tiger salamanders from a sewage lagoon, Science, 196, 315–317.CrossRefPubMedGoogle Scholar
  57. 57.
    Khudoley, V. V., and Eliseiv, V. V. (1979) Multiple melanomas in the axolotl Ambystoma mexicanum, J. Natl. Cancer Inst., 63, 101–103.PubMedGoogle Scholar
  58. 58.
    Harshbarger, J. C., Chang, S. C., DeLanney, L. E., Rose, F. L., and Green, D. E. (1999) Cutaneous mastocytomas in the neotenic caudate amphibians Ambystoma mexicanum (axolotl) and Ambystoma tigrinum (tiger salamander), J. Cancer Res. Clin. Oncol., 125, 187–192.CrossRefPubMedGoogle Scholar
  59. 59.
    Skulachev, M. V., and Skulachev, V. P. (2017) Programmed aging of mammals: proof of concept and prospects of biochemical approaches for anti-aging therapy, Biochemistry (Moscow), 82, 1403–1422.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • V. N. Manskikh
    • 1
    • 2
    Email author
  • O. A. Averina
    • 1
    • 2
  • A. I. Nikiforova
    • 2
  1. 1.Lomonosov Moscow State UniversityBelozersky Institute of Physico-Chemical BiologyMoscowRussia
  2. 2.Lomonosov Moscow State UniversityInstitute of MitoengineeringMoscowRussia

Personalised recommendations