Skip to main content
SpringerLink
Log in

Study of age-dependent structural and functional changes of mitochondria in skeletal muscles and heart of naked mole rats (Heterocephalus glaber)

  • Phenoptosis (Special Issue)
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Morphometric analysis of mitochondria in skeletal muscles and heart of 6- and 60-month-old naked mole rats (Heterocephalus glaber) revealed a significant age-dependent increase in the total area of mitochondrial cross-sections in studied muscle fibers. For 6- and 60-month-old animals, these values were 4.8 ± 0.4 and 12.7 ± 1.8%, respectively. This effect is mainly based on an increase in the number of mitochondria. In 6-month-old naked mole rats, there were 0.23 ± 0.02 mitochondrial cross-sections per μm2 of muscle fiber, while in 60-month-old animals this value was 0.47 ± 0.03. The average area of a single mitochondrial cross-section also increased with age in skeletal muscles–from 0.21 ± 0.01 to 0.29 ± 0.03 μm2. Thus, naked mole rats show a drastic enlargement of the mitochondrial apparatus in skeletal muscles with age due to an increase in the number of mitochondria and their size. They possess a neotenic type of chondriome accompanied by specific features of mitochondrial functioning in the state of oxidative phosphorylation and a significant decrease in the level of matrix adenine nucleotides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bennett, N. C., and Faulkes, C. G. (2000) The Evolution of Sociality in African Mole-Rats, Cambridge University Press, Cambridge, UK.

    Google Scholar 

  2. Bennett, N. C., and Faulkes, C. G. (2000) Social Organization in African Mole Rats, Cambridge University Press, Cambridge, UK.

    Google Scholar 

  3. Brett, R. A. (1991) The Population Structure of Naked Mole Rat Colonies, Princeton University Press, Princeton, NJ.

    Google Scholar 

  4. Buffenstein, R., Park, R., Hanes, M., and Antwohl, J. E. (2012) in The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents (Suckow, M. A., Stevens, K. A., and Wilson, R. P., eds.) Elsevier, London, pp. 1055–1074.

  5. Jarvis, J. U. (1981) Eusociality in a mammal: cooperative breeding in naked mole-rat colonies, Science, 212, 571–573.

    Article  CAS  PubMed  Google Scholar 

  6. Sherman, P. W., Jarvis, J. U., and Alexander, R. D. (1991) The Biology of the Naked Mole-Rat, Princeton University Press, Princeton, NJ.

    Google Scholar 

  7. Lacey, E. A., Patton, J. L., and Cameron, G. N. (2000) Life Underground: The Biology of Subterranean Rodents, University of Chicago Press, Chicago, IL.

    Google Scholar 

  8. Delaney, M. A., Nagy, L., Kinsel, M. J., and Treuting, P. M. (2013) Spontaneous histologic lesions of the adult naked mole rat (Heterocephalus glaber): a retrospective survey of lesions in a zoo population, Vet. Pathol., 50, 607–621.

    Article  CAS  PubMed  Google Scholar 

  9. Buffenstein, R. (2000) Ecological and Physiological Responses to Underground Habitats, University of Chicago Press, Chicago, IL.

    Google Scholar 

  10. Larson, J., and Park, T. J. (2009) Extreme hypoxia tolerance of naked mole rat brain, Neuroreport, 20, 1634–1637.

    Article  PubMed  Google Scholar 

  11. Maina, J. N., Gebreegziabher, Y., Woodley, R., and Buffenstein, R. (2001) Effects of change in environmental temperature and natural shifts in carbon dioxide and oxygen concentrations on the lungs of captive naked mole rats (Heterocephalus glaber): a morphological and morphometric study, J. Zool., 253, 371–382.

    Article  Google Scholar 

  12. Park, T. J., Lu, Y., Juttner, R., Smith, E. S., Hu, J., Brand, A., Wetzel, C., Milenkovic, N., Erdmann, B., Heppenstall, P. A., Laurito, C. E., Wilson, S. P., and Lewin, G. R. (2008) Selective inflammatory pain insensitivity in the African naked mole rat (Heterocephalus glaber), PLoS Biol., 6, e13.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Buffenstein, R. (2008) Negligible senescence in the longest living rodent, the naked mole rat: insights from a successfully aging species, J. Comp. Physiol. B, 178, 439–445.

    Article  PubMed  Google Scholar 

  14. Harman, D. (1956) Aging: a theory based on free radical and radiation chemistry, J. Gerontol., 11, 298–300.

    Article  CAS  PubMed  Google Scholar 

  15. Lenaz, G. (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology, IUBMB Life, 52, 159–164.

    Article  CAS  PubMed  Google Scholar 

  16. Andreyev, A. Yu., Kushnareva, Yu. E., and Starkov, A. A. (2005) Mitochondrial metabolism of reactive oxygen species, Biochemistry (Moscow), 70, 200–214.

    Article  CAS  Google Scholar 

  17. Honda, H. M., Korge, P., and Weiss, J. N. (2005) Mitochondria and ischemia/reperfusion injury, Ann. N. Y. Acad. Sci., 1047, 248–258.

    Article  CAS  PubMed  Google Scholar 

  18. Zweier, J. L., and Talukder, M. A. (2006) The role of oxidants and free radicals in reperfusion injury, Cardiovasc. Res., 70, 181–190.

    Article  CAS  PubMed  Google Scholar 

  19. Yellon, D. M., and Hausenloy, D. J. (2007) Myocardial reperfusion injury, N. Engl. J. Med., 357, 1121–1135.

    Article  CAS  PubMed  Google Scholar 

  20. Eltzschig, H. K., and Eckle, T. (2011) Ischemia and reperfusion − from mechanism to translation, Nat. Med., 17, 1391–1401.

    Article  CAS  PubMed  Google Scholar 

  21. Borutaite, V., Toleikis, A., and Brown, G. C. (2013) In the eye of the storm: mitochondrial damage during heart and brain ischemia, FEBS J., 280, 4999–5014.

    Article  CAS  PubMed  Google Scholar 

  22. Chouchani, E. T., Pell, V. R., Gaude, E., Aksentijevic, D., Sundier, S. Y., Robb, E. L., Logan, A., Nadtochiy, S. M., Ord, E. N., Smith, A. C., Eyassu, F., Shirley, R., Hu, C. H., Dare, A. J., James, A. M., Rogatti, S., Hartley, R. C., Eaton, S., Costa, A. S., Brookes, P. S., Davidson, S. M., Duchen, M. R., Saeb-Parsy, K., Shattock, M. J., Robinson, A. J., Work, L. M., Frezza, C., Krieg, T., and Murphy, M. P. (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS, Nature, 515, 431–435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Harman, D. (1972) The biologic clock: the mitochondria? J. Am. Geriatr. Soc., 20, 145–147.

    Article  CAS  PubMed  Google Scholar 

  24. Miquel, J., Economos, A. C., Fleming, J., and Johnson, J. E. (1980) Mitochondrial role in cell aging, Exp. Gerontol., 15, 575–591.

    Article  CAS  PubMed  Google Scholar 

  25. Skulachev, V. P. (1997) Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann’s hypothesis, Biochemistry (Moscow), 62, 1191–1195.

    CAS  Google Scholar 

  26. Skulachev, V. P. (1999) Phenoptosis: programmed death of an organism, Biochemistry (Moscow), 64, 1418–1426.

    CAS  Google Scholar 

  27. Skulachev, V. P. (2001) Phenomena of programmed death. Mitochondria, cells and organs: role of reactive oxygen species, Soros. Obraz. Zh., 7, 4–10.

    Google Scholar 

  28. Labinskyy, N., Csiszar, A., Orosz, Z., Smith, K., Rivera, A., Buffenstein, R., and Ungvari, Z. (2006) Comparison of endothelial function, O2 – and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice, Am. J. Physiol. Heart. Circ. Physiol., 291, H2698–2704.

    Article  CAS  PubMed  Google Scholar 

  29. Lambert, A. J., Boysen, H. M., Buckingham, J. A., Yang, T., Podlutsky, A., Austad, S. N., Kunz, T. H., Buffenstein, R., and Brand, M. D. (2007) Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms, Aging Cell, 65, 607–618.

    Article  Google Scholar 

  30. Csiszar, A., Labinskyy, N., Orosz, Z., Xiangmin, Z., Buffenstein, R., and Ungvari, Z. (2007) Vascular aging in the longest-living rodent, the naked mole rat, Am. J. Physiol. Heart. Circ. Physiol., 293, H919–927.

    Article  CAS  PubMed  Google Scholar 

  31. Vays, V. B., Eldarov, C. M., Vangely, I. M., Kolosova, N. G., Bakeeva, L. E., and Skulachev, V. P. (2014) Antioxidant SkQ1 delays sarcopenia-associated damage of mitochondrial ultrastructure, Aging (Albany, NY), 6, 140–148.

    Article  Google Scholar 

  32. Carter, H. N., Chen, C. C. W., and Hood, D. A. (2015) Mitochondria, muscle health, and exercise with advancing age, Physiology, 30, 208–223.

    Article  CAS  PubMed  Google Scholar 

  33. Del Campo, A., Jaimovich, E., and Tevy, M. F. (2016) Mitochondria in the aging muscles of flies and mice: new perspectives for old characters, Oxid. Med. Cell. Longev., 2016, 9057593.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Onyango, D. W., and Oduorokelo, D. (1993) Ultrastructural study of the testis of non-breeding naked mole-rat (Heterocephalus glaber Ruppell), Ann. Anat., 175, 447–452.

    Article  CAS  PubMed  Google Scholar 

  35. Brovko, L., Romanova, N. A., and Ugarova, N. N. (1994) Bioluminescent assay of bacterial intracellular AMP, ADP, and ATP with the use of a coimmobilized three-enzyme reagent (adenylate kinase, pyruvate kinase, and firefly luciferase), Anal. Biochem., 220, 410–414.

    Article  CAS  PubMed  Google Scholar 

  36. Reynolds, E. S. (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy, J. Cell Biol., 17, 208–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bakeeva, L. E., Chentsov, Y. S., and Skulachev, V. P. (1981) Ontogenesis of mitochondrial reticulum in rat diaphragm muscle, Eur. J. Cell. Biol., 25, 175–181.

    CAS  PubMed  Google Scholar 

  38. Bakeeva, L. E. (2015) Age-related changes in ultrastructure of mitochondria. Effect of SkQ1, Biochemistry (Moscow), 80, 1582–1588.

    Article  CAS  Google Scholar 

  39. Glagolev, A. A. (1941) Geometric Methods of Quantitative Analysis of Aggregates under the Microscope [in Russian], Gosgeolizdat, Moscow.

    Google Scholar 

  40. McCallister, B. D., and Brown, A. L. (1965) A quantitative study of myocardial mitochondria in experimental cardiac hypertrophy, Lab. Invest., 14, 692–700.

    CAS  PubMed  Google Scholar 

  41. McCallister, L. P., and Page, E. (1973) Effects of thyroxin on ultrastructure of rat myocardial cells: a stereological study, J. Ultrastruct. Res., 42, 136–55.

    Article  CAS  PubMed  Google Scholar 

  42. McCallister, L. P., Page, E., and Power, B. (1971) Stereological measurements of cardiac ultrastructures implicated in excitation–contraction coupling, Proc. Natl. Acad. Sci. USA, 68, 1465–1466.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Weibel, E. R. (1979) Stereological Methods. Vol. 1. Practical Methods for Biological Morphometry, Academic Press, London.

    Google Scholar 

  44. Sachs, H. G., Colgan, J. A., and Lazarus, M. L. (1977) Ultrastructure of the aging myocardium: a morphometric approach, Am. J. Anat., 150, 63–71.

    Article  CAS  PubMed  Google Scholar 

  45. Frenzel, H., and Feimann, J. (1984) Age-dependent structural changes in the myocardium of rats. A quantitative light- and electron-microscopic study on the right and left chamber wall, Mech. Ageing Dev., 27, 29–41.

    Article  CAS  PubMed  Google Scholar 

  46. Maina, J. N. (1988) Morphology and morphometry of the normal lung of the adult vervet monkey (Cercopithecus aethiops), Am. J. Anat., 183, 258–267.

    Article  CAS  PubMed  Google Scholar 

  47. Maina, J. N. (2002) Some recent advances on the study and understanding of the functional design of the avian lung: morphological and morphometric perspectives, Biol. Rev. Camb. Philos. Soc., 77, 97–152.

    Article  CAS  PubMed  Google Scholar 

  48. Maina, J. N., and King, A. S. (1987) A morphometric study of the lung of a Humboldt penguin (Sphenicus humboldti), Anat. Histol. Embryol., 16, 293–297.

    CAS  PubMed  Google Scholar 

  49. Maina, J. N., and Nathaniel, C. (2001) A qualitative and quantitative study of the lung of an ostrich Struthio camelus, J. Exp. Biol., 204, 2313–2330.

    CAS  PubMed  Google Scholar 

  50. Maina, J. N., and Van Gils, P. (2001) Morphometric characterization of the airway and vascular systems of the lung of the domestic pig Sus scrofa: comparison of the airway, arterial and venous systems, Comp. Biochem. Physiol. A Mol. Integr. Physiol., 130, 781–798.

    Article  CAS  PubMed  Google Scholar 

  51. Aprille, J. R., and Asimakis, G. K. (1980) Postnatal-development of rat-liver mitochondria-state-3 respiration, adenine nucleotide translocase activity, and the net accumulation of adenine nucleotides, Arch. Biochem. Biophys., 201, 564–575.

    Article  CAS  PubMed  Google Scholar 

  52. Korshunov, S. S., Skulachev, V. P., and Starkov, A. A. (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria, FEBS Lett., 416, 15–18.

    Article  CAS  PubMed  Google Scholar 

  53. Marzetti, E., Hwang, J. C. Y., Lees, H. A., Wohlgemuth, S. E., Dupont-Versteegden, E. E., Carter, C. S., Bernabei, R., and Leeuwenburgha, C. (2010) Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy, Biochim. Biophys. Acta, 1800, 235–244.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Leibniz Institute for Zoo and Wildlife Research, Department of Reproduction Management, 10315, Berlin, Germany

    S. Holtze & T. B. Hildebrandt

  2. Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991, Moscow, Russia

    C. M. Eldarov, V. B. Vays, I. M. Vangeli, M. Yu. Vysokikh, L. E. Bakeeva & V. P. Skulachev

Authors
  1. S. Holtze
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. M. Eldarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. B. Vays
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. M. Vangeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Yu. Vysokikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. E. Bakeeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. P. Skulachev
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. B. Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to S. Holtze, M. Yu. Vysokikh or L. E. Bakeeva.

Additional information

Original Russian Text © S. Holtze, C. M. Eldarov, V. B. Vays, I. M. Vangeli, M. Yu. Vysokikh, L. E. Bakeeva, V. P. Skulachev, T. B. Hildebrandt, 2016, published in Biokhimiya, 2016, Vol. 81, No. 12, pp. 1703–1712.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holtze, S., Eldarov, C.M., Vays, V.B. et al. Study of age-dependent structural and functional changes of mitochondria in skeletal muscles and heart of naked mole rats (Heterocephalus glaber). Biochemistry Moscow 81, 1429–1437 (2016). https://doi.org/10.1134/S000629791612004X

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S000629791612004X

Key words

Search

Navigation