Morphological characteristics and molecular mechanisms of pathogenesis of aging cardiac muscle

• Kogan E.A.
• Akulova A.S.
• Syrkin A.L.

Abstract

Cardiovascular diseases (CVD) remain the main cause of death in the world, 17.9 million people die from them annually. Data on the aging of postmitotic cells has appeared recently as a result of the work of several laboratories. These cells are called amitosenescent cells. The main morphological and molecular criteria used to identify cells undergoing either replicative aging or premature aging caused by stress are discussed. The study of aging cells will help to find approaches to increase the duration of life and therapy of diseases in old age. The aim of the work is to review the literature on morphological features and molecular biological mechanisms of aging myocardium. The theories of aging and their role in myocardial aging are considered. The theory of autophagy is of the greatest importance in myocardial aging, since its suppression leads to an acceleration of degenerative cellular processes in the myocardium; it is also necessary to single out telomeric theory as a common mechanism of aging, undoubtedly affecting the preservation of cardiomyocytes. The lack of repair in cardiomyocytes, associated with their amitosenescence, leads to increased DNA damage and has an adverse effect on cell life expectancy. The aging processes of the heart are accompanied by a progressive decrease in physiological functions, which is the most common cause of death in the elderly. Suppression of changes in the cardiovascular system accompanying aging may reduce the risk of age-related diseases.

Keywords:aging myocardium; senescent cells; amitosenescence; molecular and morphological markers of senescent cell; pathogenesis of diseases in old age

References

1.     World Health Organization (WHO): official website. Cardiovascular diseases [Electronic resource]. URL: www.who.int  (date of access July 01, 2023).

2.     Global atlas on cardiovascular disease prevention and control. Policies, strategies and interventions. Geneva: World Health Organization, 2013. ISBN 978-9-24456-437-0.

3.     Unified interdepartmental information and statistical system (EMISS): official website. Mortality due to cardiovascular diseases, malignancies, diabetes mellitus, chronic respiratory diseases [Electronic resource]. URL: www.fedstat.ru  (date of access July 01, 2023). (in Russian)

4.     Lazzeroni D., Villatore A., Souryal G., Pili G., Peretto G. The aging heart: a molecular and clinical challenge. Int J Mol Sci. 2022; 23 (24): 16033. DOI: https://doi.org/10.3390/ijms232416033  PMID: 36555671; PMCID: PMC9783309.

5.     Federal state statistics service (Rosstat). Healthcare in Russia, 2019: statistical collection. Moscow, 2019: 169 p. ISBN 978-5-89476-470-2. (in Russian)

6.     Rodier F., Campisi J. Four faces of cellular senescence. J Cell Biol. 2011; 192 (4): 547–56. DOI: https://doi.org/10.1083/jcb.201009094  

7.     Shirakabe A., Ikeda Y., Sciarretta S., Zablocki D.K., Sadoshima J. Aging and autophagy in the heart. Circ Res. 2016; 118 (10): 1563–76. DOI: https://doi.org/10.1161/CIRCRESAHA.116.307474  

8.     Akasheva D.U., Strazhesko I.D., Dudinskaya E.N., Naydenko E.V., Tkacheva E.N. Heart and age (part I): theories of aging, morphological changes. Kardiovaskulyarnaya terapiya i profilaktika [Cardiovascular Therapy and Prevention]. 2013; 12 (1): 88–94. DOI: https://doi.org/10.15829/1728-8800-2013-1-88-94  (in Russian)

9.     Young A.T., Lakey J.R., Murray A.G., et al. In vitro senescence occurring in normal human endothelial cells can be rescued by ectopic telomerase activity. Transplant Proc. 2003; 35: 2483–5. DOI: https://doi.org/10.1016/j.transproceed.2003.08.032  

10. Collerton J., Martin-Ruiz C., Kenny A., et al. Telomere length is associated with left ventricular function in the oldest old: the Newcastle 85+ study. Eur Heart J. 2007; 28: 172–6. DOI: https://doi.org/10.1093/eurheartj/ehl437  

11. Matthews C., Gorenne I., Scott S., et al. Vascular smoothmuscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res. 2006; 99: 156–64. DOI: https://doi.org/10.1161/01.RES.0000233315.38086.bc  

12. Tombor B., Rundell K., Oltvai Z.N. Bcl-2 promotes premature senescence induced by oncogenic Ras. Biochem Biophys Res Commun. 2003; 303 (3): 800–7. DOI: https://doi.org/10.1016/s0006-291x(03)00402-9  

13. Papanagnou E.D., Gumeni S., Sklirou A.D., Rafeletou A., Terpos E., Keklikoglou K., et al. Autophagy activation can partially rescue proteasome dysfunction-mediated cardiac toxicity. Aging Cell. 2022; 21 (11): e13715. DOI: https://doi.org/10.1111/acel.13715  Epub 2022 Oct 19. PMID: 36259256; PMCID: PMC9649605.

14. Baryshnikov A.Yu., Shishkin Yu.V. Immunological problems of apoptosis. Moscow: Editorial URSS, 2002: 318 p. ISBN 5-8360-0328-9. (in Russian)

15. Romodin L.A., Vladimirov Yu.A. Cytochrome C as a facultative enzyme-mitochondrial lipoperoxidase. Vestnik novykh meditsinskikh tekhnologiy [Bulletin of New Medical Technologies]. 2020; 27 (4): 102–5. DOI: https://doi.org/10.24411/1609-2163-2020-16679  (in Russian)

16. Gacko M., Trochimczuk A., Ostrowska H. Udział enzymów proteolitycznych w apoptozie [The role of proteolytic enzymes in apoptosis]. Postepy Hig Med Dosw. 1998; 52 (6): 601–19. PMID: 10093479. (in Polish)

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