From cellular senescence towards age-related macular degeneration: the role of telomeres
DOI: 10.32364/2311-7729-2020-20-3-148-151
From cellular senescence towards age-related macular degeneration: the role of telomeres
L.K. Moshetova1, O.I. Abramova1, K.I. Turkina1, O.P. Dmitrenko2, N.S. Karpova2
1Russian Medical Academy of Continuous Professional Education, Moscow,
Russian Federation
2Institute of General Pathology and Pathophysiology, Moscow, Russian Federatios
Since the discovery, telomeres and telomerase have been extensively studied, at first, as a mechanism of cellular senescence, and then, as human health and disease indicators. Telomeres that protect chromosomal ends play a vital role in genomic stability by preserving information.
This article reviews the results of early studies that later became the basis for further in-depth experiments. Studies that demonstrate the association between telomere shortening and the development of neurodegenerative disorders, e.g., age-related macular degeneration (AMD), are addressed as well. In addition, authors discuss the mechanisms of cellular senescence as a result of telomere attrition. The understanding of molecular mechanisms involved in aging may provide innovative therapeutic and preventive strategies for AMD. This disease is the third leading cause of blindness in elderly patients after glaucoma and cataract. AMD is diagnosed by typical retinal lesions in persons over 50 years. The prevalence of dry and wet AMD varies among ethnic and racial groups worldwide. Various types, stages, and prevalence of the disease may be seen in the same age group. These findings demonstrate the need for a biomarker to monitor the process of aging underlying AMD as well as potential explanations for the differences in its course and outcomes.
Keywords: aging, cellular senescence, telomeres, telomere shortening, age-related macular degeneration, aging-associated diseases, sirtuins.
For citation: Moshetova L.K., Abramova O.I., Turkina K.I. et al. From cellular senescence towards age-related macular degeneration: the role of telomeres. Russian Journal of Clinical Ophthalmology. 2020;20(3):148–151. DOI: 10.32364/2311-7729-2020-20-3-148-151.
2. Libertini G. Non-programmed versus programmed aging paradigm. Curr Aging Sci. 2015;8(1):56–68. DOI: 10.2174/1874609808666150422111623.
3. Libertini G., Ferrara N. Aging of perennial cells and organ parts according to the programmed aging paradigm. Age (Dordr). 2016;38(2):35. DOI: 10.1007/s11357-016-9895-0.
4. Perona R., Iarriccio L., Pintado-Berninches L. et al. Molecular diagnosis and precission therapeutic approaches for telomere biology disorders. Telomeres: INTECH. 2016;77–117. DOI: 10.5772/65353.
5. Sanders J.L., Newman A.B. Telomere length in epidemiology: a biomarker of aging, age-related disease, both, or neither? Epidemiol. Rev. 2013;35:112–131. DOI: 10.1093/epirev/mxs008.
6. Bernadotte A., Mikhelson V.M., Spivak I.M. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY). 2016;8(1):3–11. DOI: 10.18632/aging.100871.
7. Lu W., Zhang Y., Liu D. et al. Telomeres-structure, function, and regulation. Exp Cell Res. 2013;319(2):133–141. DOI: 10.1016/j.yexcr.2012.09.005.
8. López-Otín C., Blasco M.A., Partridge L. et al. The hallmarks of aging. Cell. 2013;153(6):1194–1217. DOI: 10.1016/j.cell.2013.05.039.
9. Martínez P., Blasco M.A. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017;216(4):875–887. DOI: 10.1083/jcb.201610111.
10. Zhdanova N.S., Rubtsov N.B. Telomere Recombination in Normal Mammalian Cells. Genetika. 2016;52(1):14–23. DOI: 10.7868/S0016675816010148.
11. Bodnar A.G., Ouellette M., Frolkis M. et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279(5349):349–352. DOI: 10.1126/science.279.5349.349.
12. Counter C.M., Meyerson M., Eaton E.N. et al. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene. 1998;16(9):1217–1222. DOI: 10.1038/sj.onc.1201882.
13. Vaziri H., Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol. 1998;8(5):279–282. DOI: 10.1016/s0960-9822 (98) 70109-5.
14. De Punder K., Heim C., Wadhwa P.D., Entringer S. Stress and immunosenescence: The role of telomerase. Psychoneuroendocrinology. 2019;101:87–100. DOI: 10.1016/j.psyneuen.2018.10.019.
15. Dey A., Chakrabarti K. Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites. Int J Mol Sci. 2018;19(2):333. DOI: 10.3390/ijms19020333.
16. Tchkonia T., Zhu Y., van Deursen J. et al. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013;123(3):966–972. DOI: 10.1172/JCI64098.
17. Shay J.W.. Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discov. 2016;6(6):584–593. DOI: 10.1158/2159-8290.CD-16-0062.
18. Lee S.H., Lee J.H., Lee H.Y., Min K.J. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019;52(1):24–34. DOI: 10.5483/BMBRep.2019.52.1.290.
19. Cardus A., Uryga A.K., Walters G., Erusalimsky J.D. SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res. 2013;97(3):571–579. DOI: 10.1093/cvr/cvs352.
20. Grabowska W., Sikora E., Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017;18(4):447–476. DOI: 10.1007/s10522-017-9685-9.
21. Hisayuki Amano H., Sahin E. Telomeres and sirtuins: at the end we meet again. Mol Cell Oncol. 2019;6(5): e1632613. DOI: 10.1080/23723556.2019.1632613.
22. Amano H., Chaudhury A., Rodriguez-Aguayo C. et al. Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease. Cell Metab. 2019;29(6):1274–1290. DOI: 10.1016/j.cmet.2019.03.001.
23. Lambert N.G., ElShelmani H., Singh M.K. et al. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res. 2016;54:64–102. DOI: 10.1016/j.preteyeres.2016.04.003.
24. Curcio C.A. Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies. Invest Ophthalmol Vis Sci. 2018;59(4):160–181. DOI: 10.1167/iovs.18-24882.
25. Weng X., Zhang H., Kan M. et al. Leukocyte telomere length is associated with advanced age-related macular degeneration in the Han Chinese population. Exp Gerontol. 2015;69:36–40. DOI: 10.1016/j.exger.2015.06.004.
26. Immonen I., Seitsonen S., Saionmaa O., Fyhrquist F. Leucocyte telomere length in age-related macular degeneration. Acta Ophthalmol. 2013;91(5):453–456. DOI: 10.1111/j.1755-3768.2012.02427.x.
27. Bär C., Blasco M.A. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases. F1000Res. 2016;5:89. DOI: 10.12688/f1000research.7020.1.
28. Varela E., Muñoz-Lorente M.A., Tejera A.M. et al. Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations. Nat Commun. 2016;7:11739. DOI: 10.1038/ncomms11739.
29. Ramunas J., Yakubov E., Brady J.J. et al. Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells. FASEB J. 2015;29(5):1930–1939. DOI: 10.1096/fj.14-259531.
30. Harley C.B., Liu W., Flom P.L., Raffaele J.M. A natural product telomerase activator as part of a health maintenance program: metabolic and cardiovascular response. Rejuvenation Res. 2013;16(5):386–395. DOI: 10.1089/rej.2013.1430.
31. Dow C.T., Harley C.B. Evaluation of an oral telomerase activator for early age-related macular degeneration — a pilot study. Clin Ophthalmol. 2016;10:243–249. DOI: 10.2147/OPTH.S100042.
32. Dong X.X., Hui Z.J., Xiang W.X. et al. Ginkgo biloba extract reduces endothelial progenitor-cell senescence through augmentation of telomerase activity. J Cardiovasc Pharmacol. 2007;49(2):111–115. DOI: 10.1097/FJC.0b013e31802ef519.
33. Rastmanesh R. Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity. Med Hypotheses. 2011;76(1):79–85. DOI: 10.1016/j.mehy.2010.08.036.
34. Boccardi V., Esposito A., Rizzo M.R. et al. Mediterranean diet, telomere maintenance and health status among elderly. PLoS One. 2013;8(4): e62781. DOI: 10.1371/journal.pone.0062781.
35. Crous-Bou M., Fung T.T., Prescott J. et al. Mediterranean diet and telomere length in Nurses’ Health Study: population based cohort study. BMJ. 2014;349: g6674. DOI: 10.1136/bmj.g6674.
36. Жумагул М.Ж., Кыдырбаева А.К., Танеева Г.Т. и др. Влияние эпигенетических факторов на укорочение теломер. Вестник КазНМУ. 2018;1:457–459. [Zhumagul M.Z., Kydyrbaeva A.K., Taneyeva G.T. et al. Influence of epigenetic factors on the short-termination. Vestnik KazNMU. 2018;1:457–459 (in Russ.)]. DOI: 10.24412/FhbsrgA3j8I.
37. Nashine S., Nesburn A.B., Kuppermann B.D., Kenney M.C. Role of Resveratrol in Transmitochondrial AMD RPE Cells. Nutrients. 2020;12(1):159. DOI: 10.3390/nu12010159.
38. Yang Y., Wu Z.Z., Cheng Y.L. et al. Resveratrol protects against oxidative damage of retinal pigment epithelium cells by modulating SOD/MDA activity and activating Bcl-2 expression. Eur Rev Med Pharmacol Sci. 2019;23(1):378–388. DOI: 10.26355/eurrev_201901_16786.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
