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A Comparative Analysis of Age-Related Changes in the Structure of the Mitochondrial Apparatus in Skeletal Muscles of Species with Different Lifespan

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Abstract

A comparative electron microscopic and morphometric analysis of age-related transformations in the ultrastructure of the skeletal muscle mitochondrial apparatus was carried out in animal species with different aging programs: short-lived classical objects, such as C57BL/6 mice and Wistar rats, prematurely aging OXYS rats, and the longest-living rodents, naked mole-rats (Heterocephalus glaber), characterized by delayed aging. In C57BL/6 mice, age-related reorganization of the skeletal muscle mitochondrial apparatus corresponds to that reported previously for Wistar rats: the mitochondrial reticulum forms by the age of 2.5–3 months; by the age of 30 months, it undergoes a drastic reduction, due to which the number of mitochondrial cross-sections in muscle fibers decreases almost twofold, from 0.45 ± 0.074 to 0.23 ± 0.017 profiles per µm2. In C57BL/6 mice, no destructive changes in the mitochondrial ultrastructure were observed, in contrast to OXYS rats, in which age-related changes in the chondriome affect both the overall structure and internal ultrastructure of the muscle fiber mitochondrial apparatus. At the same time, in naked mole-rats, which are comparable with mice in their size, the number and size of mitochondria in skeletal muscles increase significantly by the age of five years, although no mitochondrial reticulum forms. It is hypothesized that a special organization of the mitochondrial apparatus in naked mole-rat skeletal muscles provide a proper level of redox processes in muscles, thus preventing a decline in their physical efficiency and the development of sarcopenia, whereas in C57BL/6 mice, Wistar and OXYS rats, age-related abnormalities in the structural organization of skeletal muscle mitochondrial apparatus may be one of the major causes for the development of age-related pathologies, including sarcopenia.

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REFERENCES

  1. Baumann CW, Kwak D, Liu HM, Thompson VL (2016) Age-induced oxidative stress: How does it influence skeletal muscle quantity and quality? J Appl Physiol 121:1047-1052. https://doi.org/10.1152/japplphysiol.00321.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brunk UT, Terman A (2002) The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269:1996–2002. https://doi.org/10.1046/j.1432-1033.2002.02869.x

    Article  CAS  PubMed  Google Scholar 

  3. Derbré F, Gratas-Delamarche A, Gómez-Cabrera MC, Viña J (2014) Inactivity-induced oxidative stress: A central role in age-related sarcopenia? Eur J Sport Sci 14:98–108. https://doi.org/10.1080/17461391.2011.654268

    Article  Google Scholar 

  4. Gamboa JL, Billings FT, Bojanowski MT, Gilliam LA, Yu C, Roshanravan B, Roberts LJ, Himmelfarb J, Ikizler TA, Brown NJ (2016) Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep 4(9):e12780. https://doi.org/10.14814/phy2.12780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Santos LS, Baraibar MA, Lundberg S, Eeg-Olofsson O, Larsson L, Friguet B (2015) Oxidative proteome alterations during skeletal muscle ageing. Redox Biol 5:267–274. https://doi.org/10.1016/j.redox.2015.05.006

    Article  CAS  Google Scholar 

  6. https://doi.org/10.1016/j.semcdb.2016.08.003

    Article  CAS  PubMed  Google Scholar 

  7. Rygiel KA, Picard M, Turnbull DM (2016) The ageing neuromuscular system and sarcopenia: a mitochondrial perspective. J Physiol 594:4499–4512. https://doi.org/10.1113/JP271212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dai DF, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS (2014) Mitochondrial oxidative stress in aging and healthspan. Longev Heal 3:6. https://doi.org/10.1186/2046-2395-3-6

    Article  Google Scholar 

  9. Johnson ML, Robinson MM, Nair KS (2013) Skeletal muscle aging and the mitochondrion. Trends Endocrinol Metab 24:247–256. https://doi.org/10.1016/j.tem.2012.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sacktor B, Shimada Y (1972) Degenerative changes in the mitochondria of flight muscle from aging blowflies. J Cell Biol 52:465-477. https://doi.org/10.1083/jcb.52.2.465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bakeeva LE, Saprunova VB, Pasyukova EG, Roshina NV (2007) Mitoptosis in the flight muscle of Drosophila melanogaster. Acad Sci Rep 413:1-3 (In Russ). https://doi.org/10.1134/S0012496607020111

    Article  Google Scholar 

  12. Williams CM, Barness LA, Sawyer WH (1943) The utilization of glycogen by flies during flight and some aspects of the physiological ageing of Drosophila. Biol Bull (Woods Hole) 84:263-268. https://doi.org/10.2307/1538009

    Article  CAS  Google Scholar 

  13. Walker DW, Benzer S (2004) Mitochondrial “swirls” induced by oxygen stress and in the Drosophila mutant hyperswirl. Proc Natl Acad Sci USA 101:10290–10295. https://doi.org/10.1073/pnas.0403767101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Anisimov VN, Bakeeva LE, Egormin PA, Filenko OF, Isakova EF, Manskikh VN, Mikhelson VM, Panteleeva AA, Pilipenko DI, Piskunova TS, Popovich IG, Saprunova VB, Samoylova TA, Semenchenko AV, Skulachev MV, Tyndyk ML, Vyssokikh MY, Yurova MN, Zabezhinsky MA, Skulachev VP (2008) Mitochondria- targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence. Biochemistry (Moscow) 73:1329-1342. https://doi.org/10.1134/s0006297908120055

    Article  CAS  Google Scholar 

  15. Beregi E, Regius O, Huttl T, Gobl Z (1988) Age-related changes in the skeletal muscle cells. Z Gerontol 21:83-86. PMID: 2968024

    CAS  PubMed  Google Scholar 

  16. Bakarev MA, Nepomnyashchikh LM (2004) Structural manifestations of mitochondrial dysfunction in skeletal muscles in premature aging OXYS rats. Bull Exp Biol Med 138:674-679 (In Russ). eLIBRARY ID: 28932383

    Article  Google Scholar 

  17. https://doi.org/10.1016/j.amjcard.2008.02.078

    Article  CAS  PubMed  Google Scholar 

  18. Crane JD, Devries C, Safdar A, Hamadeh MJ, Tarnopolsky MA (2010) The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J Gerontol 65:119-128. https://doi.org/10.1101/cshperspect.a029785

    Article  CAS  Google Scholar 

  19. Orlander J, Kiessling K, Larsson L, Karlsson J, Aniansson A (1978) Skeletal muscle metabolism and ultrastructure in relation to age in sedentary men. Acta Physiol Scand 104:249-261. https://doi.org/10.1111/j.1748-1716.1978.tb06277.x

    Article  CAS  PubMed  Google Scholar 

  20. Palade GE (1956) Electron microscopy of mitochondria and other cytoplasmic structures. In: Enzymes: Units of Biological Structure and Function. Acad Press New York 185-215.

    Google Scholar 

  21. Gauthier GF, Padykula HA (1966) Cytological studies of fiber types in skeletal muscle. A comparative study of the mammalian diaphragm. J Cell Biol 28:333-354. https://doi.org/10.1083/jcb.28.2.333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bubenzer HJ (1966) Die dunnen und die dicken Muskelfasern des Zwerchfells der Ratte. Z Zellforsch 69:520-550. https://doi.org/10.1007/BF00406300

    Article  CAS  PubMed  Google Scholar 

  23. Bakeeva LE, Skulachev VP, Chentsov YS (1978) Mitochondrial framework (reticulum mitochondriale) in rat diaphragm muscle. Biochim Biophys Acta 501:349-369. https://doi.org/10.1016/0005-2728(78)90104-4

    Article  CAS  PubMed  Google Scholar 

  24. Bakeeva LE, Chentsov YS, Skulachev VP (1981) Ontogenesis of mitochondrial reticulum in rat diaphragm muscle. Eur J Cell Biol 25:175-181. PMID: 7285951

    CAS  PubMed  Google Scholar 

  25. Kirkwood SP, Munn EA, Brooks GA (1986) Mitochondrial reticulum in limb skeletal muscle. Am J Physiol 251:395-402. https://doi.org/10.1152/ajpcell.1986.251.3.C395

    Article  Google Scholar 

  26. Glancy B, Hartnell LM, Malide D, Yu ZX, Combs CA, Connelly PS, Subramaniam S, Balaban RS (2015) Mitochondrial reticulum for cellular energy distribution in muscle. Nature 523:617-620. https://doi.org/10.1038/nature14614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pellegrini G, Barbieri S, Moggio M, Cheldi A, Scarlato G, Minetti C (1985) A case of congenital neuromuscular disease with uniform type I fibers, abnormal mitochondrial network and jagged Z-line. Neuropediatrics 16:162-166. https://doi.org/10.1055/s-2008-1059533

    Article  CAS  PubMed  Google Scholar 

  28. Leduc-Gaudet JP, Picard M, Pelletier FSt-J, Sgarioto N, Auger MJ, Vallée J, Robitaille R, St-Pierre DH, Gouspillou G (2015) Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget 6:17923-17937. https://doi.org/10.18632/oncotarget.4235

    Article  PubMed  PubMed Central  Google Scholar 

  29. Buffenstein R. (2008) Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. Compar Physiol B 178:439–445. https://doi.org/10.1007/s00360-007-0237-5

    Article  Google Scholar 

  30. Orr ME, Garbarino VR, Salinas A, Buffenstein R (2015) Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent. Neurobiol Aging 36:1496–1504. https://doi.org/10.1016/j.neurobiolaging.2014.12.004

    Article  CAS  PubMed  Google Scholar 

  31. Larson J, Park TJ (2009) Extreme hypoxia tolerance of naked mole-rat brain. Neuroreport 20:1634–1637. https://doi.org/10.1097/WNR.0b013e32833370cf

    Article  PubMed  Google Scholar 

  32. Maina JN, Gebreegziabher Y, Woodley R, 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. https://doi.org/10.1017/S0952836901000346

    Article  Google Scholar 

  33. Park TJ, Lu Y, Jüttner R, Smith EJ, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR (2008) Selective Inflammatory Pain Insensitivity in the African Naked Mole-Rat (Heterocephalus glaber). PLoS Biol January 6:13. https://doi.org/10.1371/journal.pbio.0060013

    Article  CAS  Google Scholar 

  34. Eldarov CM, Vangely IM, Kolosova NG, Bakeeva LE, Skulachev VP (2014) Antioxidant SkQ1 delays sarcopenia- associated damage of mitochondrial ultrastructure. Aging 6:140-148. https://doi.org/10.18632/aging.100636

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bakeeva LE (2015) Age-Related Changes in Ultrastructure of Mitochondria. Effect of SkQ1. Biochemistry 80:1582-8. https://doi.org/10.1134/S0006297915120068

    Article  CAS  PubMed  Google Scholar 

  36. https://doi.org/10.1016/j.bbagen.2009.05.007

    Article  CAS  PubMed  Google Scholar 

  37. Holtze S, Eldarov CM, Vays VB, Vangeli IM, Vysokikh MY, Bakeeva LE, Skulachev VP, Hildebrandt TB (2016) Study of Age-Dependent Structural and Functional Changes of Mitochondria in Skeletal Muscles and Heart of Naked Mole Rats (Heterocephalus glaber). Biochemistry 81: 1703-1712. https://doi.org/10.1134/S000629791612004

    Article  Google Scholar 

  38. Skulachev VP, Holtze S, Vyssokikh MY, Bakeeva LE, Skulachev MV, Markov AV, Hildebrandt TB, Sadovnichii VA (2017) Neoteny, prolongation of youth: from naked mole rats to “naked apes” (humans). Physiol Rev 97:699–720. https://doi.org/10.1152/physrev.00040.2015

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the Russian Foundation for Basic Research, grant No. 19-04-00578-a.

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Central idea and experimental design: L.E.B.; experimental studies: V.B.V., I.M.V.; mathematical data processing: Ch.M.E.; writing and editing a manuscript: V.B.V., I.M.V., Ch.M.E. and L.E.B.

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Correspondence to L. E. Bakeeva.

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The authors declare that they have neither evident nor potential conflict of interest related to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2021, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2021, Vol. 107, Nos. 6–7, pp. 876–894https://doi.org/10.31857/S0869813921060133.

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Vays, V.B., Vangeli, I.M., Eldarov, C.M. et al. A Comparative Analysis of Age-Related Changes in the Structure of the Mitochondrial Apparatus in Skeletal Muscles of Species with Different Lifespan. J Evol Biochem Phys 57, 730–742 (2021). https://doi.org/10.1134/S0022093021030200

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