Impact of viruses and retrotransposons on genetic instability and aging

Cover Page

Cite item

Full Text

Abstract

Preventive medicine holds significant promise for delaying and even preventing dangerous age-related pathologies. Advances in vaccine development, new preventive medications, cardiovascular implants and early diagnostic tools has increased life expectancy both in Russia and worldwide. Age-dependent genetic instability results in increased risk of developing a number of age-associated diseases. One consequence of this instability is the accumulation of senescent cells across tissues. Senescent cells lose functional activity, replacing normal cells, and are characterized by the secretion of proinflammatory cytokines, creating a chronic inflammatory background, which is the main characteristic of aging. Genetic instability is associated with higher activity of endogenous retroviruses, retrotransposons. Additionally, exogenic viruses and bacteria are able to damage cell genetic apparatus and induce disrupted transcription, translation and repair. The review discusses new approaches aimed at reducing the risk of age-related diseases by controlling genetic instability and viral infections, as well as mechanisms regulating genetic stability. Among the repercussions of disrupting such mechanisms are the development of proliferative, neurodegenerative diseases, cellular senescence and their contribution to chronic inflammation. Antiviral medications and compounds that suppress the activity of endogenous reverse transcriptases are proposed as promising preventive agents for suppressing age-related genetic instability. Although such substances are already used in the clinic to control human immunodeficiency virus, there are currently no medications suitable for long-term use without significant side effects. In this regard, it is primarily important to develop new generation medications that could be used as preventive agents and would meet efficacy and safety requirements, with minimal side effects. The review also explores other promising approaches such as senolytics (agents that selectively eliminate senescent cells) and senomorphics (substances that suppress proinflammatory in prevention of age-associated pathologies. Another perspective method for preventing genetic instability and accumulation of senescent cells is a search for highly specific targets and the development of immunization approaches that allow immune system to remove damaged and senescent cells with increased genetic instability. The proposed approaches can prolong health span and reduce the burden on healthcare system.

About the authors

Elena V. Lysakova

Sirius University of Science and Technology

Author for correspondence.
Email: helena.llysakova@mail.ru

PhD Student, Junior Researcher, Division of Immunobiology and Biomedicine

Russian Federation, Sirius Federal Territory, Krasnodar Region

Marina Y. Burak

Sirius University of Science and Technology

Email: marina.burak188@mail.ru

Мaster’s degree Student

Russian Federation, Sirius Federal Territory, Krasnodar Region

Maxim B. Navrotsky

Sirius University of Science and Technology

Email: navrotskij.mb@talantiuspeh.ru

PhD (Pharmacy), Head of the Medical Chemistry Group, Division of Medical Biotechnology

Russian Federation, Sirius Federal Territory, Krasnodar Region

Stanislav A. Rybtsov

Sirius University of Science and Technology

Email: rybtsov.sa@talantiuspeh.ru

PhD (Biology), Head of the Resource Center for Cell Technologies and Immunology

Russian Federation, Sirius Federal Territory, Krasnodar Region

References

  1. Власова О.А., Антонова И.А., Магомедова Х.М., Усолкина М.А., Кирсанов К.И., Белицкий Г.А., Якубовская М.Г. Потенциальные возможности использования в онкологии ингибиторов обратной транскриптазы вирусов // Успехи молекулярной онкологии. 2024. Т. 11. C. 8–28. [Vlasova O.A., Antonova I.A., Magomedova H.M., Usolkina M.A., Kirsanov K.I., Belitsky G.A., Yakubovskaya M.G. Potential to use of viral reverse transcriptase inhibitors in oncology. Uspekhi molekulyarnoi onkologii = Advances in Molecular Oncology, 2024, vol. 11, pp. 8–28. (In Russ.)] doi: 10.17650/2313-805x-2024-11-2-8-28
  2. Ганковская Л.В., Артемьева О.В., Греченко В.В., Насаева Е.Д., Хасанова Е.М. Возраст-ассоциированные заболевания: роль инфламмасомного комплекса // Иммунология. 2023. Т. 44, № 5. С. 640–652. [Gankovskaya L.V., Artemyeva O.V., Grechenko V.V., Nasaeva E.D., Khasanova E.M. Age-associated diseases: the role of the inflammasome complex. Immunologiya = Immunologiya, 2023, vol. 44, no. 5, pp. 640–652. (In Russ.)] doi: 10.33029/1816-2134-2023-44-5-640-652
  3. Масютина А.М., Пащенков М.В., Пинегин Б.В. Клеточное старение: механизмы и клиническое значение // Иммунология. 2024. Т. 45, № 2. С. 221–234. [Masyutina A.M., Pashenkov M.V. Cellular senescence: mechanisms and clinical implications. Immunologiya = Immunologiya, 2024, vol. 45, no. 2, pp. 221–234. (In Russ.)] doi: 10.33029/1816-2134-2024-45-2-221-234
  4. Al-Salama Z.T. Elsulfavirine: First Global Approval. Drugs, 2017, vol. 77, no. 16, pp. 1811–1816. doi: 10.1007/s40265-017-0820-3
  5. Ahmadi Ghezeldasht S., Blackbourn D.J., Mosavat A., Rezaee S.A. Pathogenicity and virulence of human T lymphotropic virus type-1 (HTLV-1) in oncogenesis: adult T-cell leukemia/lymphoma (ATLL). Crit. Rev. Clin. Lab. Sci., 2023, vol. 60, no. 3, pp. 189–211. doi: 10.1080/10408363.2022.2157791
  6. Ambati J., Magagnoli J., Leung H., Wang S.B., Andrews C.A., Fu D., Pandey A., Sahu S., Narendran S., Hirahara S., Fukuda S., Sun J., Pandya L., Ambati M., Pereira F., Varshney A., Cummings T., Hardin J.W., Edun B., Bennett C.L., Ambati K., Fowler B.J., Kerur N., Röver C., Leitinger N., Werner B.C., Stein J.D., Sutton S.S., Gelfand B.D. Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development. Nat Commun., 2020, vol. 11, no. 1: 4737. doi: 10.1038/s41467-020-18528-z
  7. Amor C., Feucht J., Leibold J., Ho Y.J., Zhu C., Alonso-Curbelo D., Mansilla-Soto J., Boyer J.A., Li X., Giavridis T., Kulick A., Houlihan S., Peerschke E., Friedman S.L., Ponomarev V., Piersigilli A., Sadelain M., Lowe S.W. Senolytic CAR T cells reverse senescence-associated pathologies. Nature, 2020, vol. 583, no. 7814, pp. 127–132. doi: 10.1038/s41586-024-07197-3
  8. Apostolova N., Funes H.A., Blas-Garcia A., Galindo M.J., Alvarez A., Esplugues J.V. Efavirenz and the CNS: what we already know and questions that need to be answered. J. Antimicrob. Chemother., 2015, vol. 70, no. 10, pp. 2693–2708. doi: 10.1093/jac/dkv183
  9. Baldwin E.T., van Eeuwen T., Hoyos D., Zalevsky A., Tchesnokov E.P., Sánchez R., Miller B.D., Di Stefano L.H., Ruiz F.X., Hancock M., Işik E., Mendez-Dorantes C., Walpole T., Nichols C., Wan P., Riento K., Halls-Kass R., Augustin M., Lammens A., Jestel A., Upla P., Xibinaku K., Congreve S., Hennink M., Rogala K.B., Schneider A.M., Fairman J.E., Christensen S.M., Desrosiers B., Bisacchi G.S., Saunders O.L., Hafeez N., Miao W., Kapeller R., Zaller D.M., Sali A., Weichenrieder O., Burns K.H., Götte M., Rout M.P., Arnold E., Greenbaum B.D., Romero D.L., LaCava J., Taylor M.S. Structures, functions and adaptations of the human LINE-1 ORF2 protein. Nature, 2024, vol. 626, no. 7997, pp. 194–206. doi: 10.1038/s41586-023-06947-z
  10. Bartolini S., Mai A., Artico M., Paesano N., Rotili D., Spadafora C., Sbardella G. 6-[1-(2,6-Difluorophenyl)ethyl]pyrimidinones Antagonize Cell Proliferation and Induce Cell Differentiation by Inhibiting (a Nontelomeric) Endogenous Reverse Transcriptase. J. Med. Chem., 2005, vol. 48, no. 22, pp. 6776–6778. doi: 10.1021/jm0507330
  11. Bhatt A.S., DeVore A.D., Hernandez A.F., Mentz R.J. Can vaccinations improve heart failure outcomes?: contemporary data and future directions. JACC Heart Fail., 2017, vol. 5, no. 3, pp. 194–203. doi: 10.1016/j.jchf.2016.12.007
  12. Bi S., Liu Z., Wu Z., Wang Z., Liu X., Wang S., Ren J., Yao Y., Zhang W., Song M., Liu G.H., Qu J. SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer. Protein Cell, 2020, vol. 11, no. 7, pp. 483–504. doi: 10.1007/s13238-020-00728-4
  13. Brenner C. Sirtuins are not conserved longevity genes. Life Metab., 2022, vol. 1, no. 2, pp. 122–133. doi: 10.1093/lifemeta/loac025
  14. Brochard T., McIntyre R.L., Houtkooper R.H., Seluanov A., Gorbunova V., Janssens G.E. Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging. Ageing Res. Rev., 2023, vol. 92: 102132. doi: 10.1016/j.arr.2023.102132
  15. Buckheit R.W. Jr., Watson K., Fliakas-Boltz V., Russell J., Loftus T.L., Osterling M.C., Turpin J.A., Pallansch L.A., White E.L., Lee J.W., Lee S.H., Oh J.W., Kwon H.S., Chung S.G., Cho E.H. SJ-3366, a unique and highly potent nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) that also inhibits HIV-2. Antimicrob. Agents Chemother., 2001, vol. 45, no. 2, pp. 393–400. doi: 10.1128/AAC.45.2.393-400.2001
  16. Budzik K.M., Nace R.A., Ikeda Y., Russell S.J. Evaluation of the stability and intratumoral delivery of foreign transgenes encoded by an oncolytic Foamy Virus vector. Cancer Gene Ther., 2022, vol. 29, no. 8–9, pp. 1240–1251. doi: 10.1038/s41417-022-00431-y
  17. Calcinotto A., Kohli J., Zagato E., Pellegrini L., Demaria M., Alimonti A. Cellular senescence: aging, cancer, and injury. Physiol. Rev., 2019, vol. 99, no. 2, pp. 1047–1078. doi: 10.1152/physrev.00020.2018
  18. Cambou M.C., Landovitz R.J. Novel antiretroviral agents. Curr. HIV/AIDS Rep., 2020, vol. 17, no. 2, pp. 118–124. doi: 10.1007/s11904-020-00486-2
  19. Chaib S., Tchkonia T., Kirkland J.L. Cellular senescence and senolytics: the path to the clinic. Nat. Med., 2022, vol. 28, no. 8, pp. 1556–1568. doi: 10.1038/s41591-022-01923-y
  20. Chan C.N., Trinité B., Levy D.N. Potent inhibition of HIV-1 replication in resting CD4 T cells by resveratrol and pterostilbene. Antimicrob. Agents Chemother., 2017, vol. 61, no. 9: e00408-17. doi: 10.1128/AAC.00408-17
  21. Childs B.G., Durik M., Baker D.J., van Deursen J.M. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat. Med., 2015, vol. 21, no. 12, pp. 1424–1435. doi: 10.1038/nm.4000
  22. Contreras-Galindo R., Dube D., Fujinaga K., Kaplan M.H., Markovitz D.M. Susceptibility of human endogenous retrovirus type K to reverse transcriptase inhibitors. J. Virol., 2017, vol. 91, no. 23: e01309-17. doi: 10.1128/JVI.01309-17
  23. Costa B., Vale N. Exploring HERV-K (HML-2) influence in cancer and prospects for therapeutic interventions. Int. J. Mol. Sci., 2023, vol. 24, no. 19: 14631. doi: 10.3390/ijms241914631
  24. Costello K.R., Leung A., Trac C., Lee M., Basam M., Pospisilik J.A., Schones D.E. Sequence features of retrotransposons allow for epigenetic variability. Elife, 2021, vol. 10: e71104. doi: 10.7554/eLife.71104
  25. Covre L.P., Martins R.F., Devine O.P., Chambers E.S., Vukmanovic-Stejic M., Silva J.A., Dietze R., Rodrigues R.R., de Matos Guedes H.L., Falqueto A., Akbar A.N., Gomes D.C.O. Circulating senescent T cells are linked to systemic inflammation and lesion size during human cutaneous leishmaniasis. Front. Immunol., 2019, vol. 9: 3001. doi: 10.3389/fimmu.2018.03001
  26. Dalwadi D.A., Kim S., Amdani S.M., Chen Z., Huang R.Q., Schetz J.A. Molecular mechanisms of serotonergic action of the HIV-1 antiretroviral efavirenz. Pharmacol. Res., 2016, vol. 110, pp. 10–24. doi: 10.1016/j.phrs.2016.04.028
  27. Dalwadi D.A., Ozuna L., Harvey B.H., Viljoen M., Schetz J.A. Adverse neuropsychiatric events and recreational use of efavirenz and other HIV-1 antiretroviral drugs. Pharmacol. Rev., 2018, vol. 70, no. 3, pp. 684–711. doi: 10.1124/pr.117.013706
  28. De Cecco M., Ito T., Petrashen A.P., Elias A.E., Skvir N.J., Criscione S.W., Caligiana A., Brocculi G., Adney E.M., Boeke J.D., Le O., Beauséjour C., Ambati J., Ambati K., Simon M., Seluanov A., Gorbunova V., Slagboom P.E., Helfand S.L., Neretti N., Sedivy J.M. L1 drives IFN in senescent cells and promotes age-associated inflammation. Nature, 2019, vol. 566, no. 7742, pp. 73–78. doi: 10.1038/s41586-018-0784-9
  29. Deeks E.D. Doravirine: first global approval. Drugs, 2018, vol. 78. no. 15, pp. 1643–1650. doi: 10.1007/s40265-018-0993-4
  30. Dembny P., Newman A.G., Singh M. Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors. JCI Insight, 2020, vol. 5, no. 7: e131093. doi: 10.1101/721241
  31. Ding L., Zhuang C., Chen F. Druggability modification strategies of the diarylpyrimidine-type non-nucleoside reverse transcriptase inhibitors. Med. Res. Rev., 2021, vol. 41, no. 3, pp. 1255–1290. doi: 10.1002/med.21760
  32. Domazet-Lošo T. mRNA vaccines: why is the biology of retroposition ignored? Genes (Basel), 2022, vol. 13, no. 5: 719. doi: 10.3390/genes13050719
  33. D’Ordine A.M., Jogl G., Sedivy J.M. Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease. Nat. Commun., 2024, vol. 15, no. 1: 3883. doi: 10.1038/s41467-024-48066-x
  34. Dupressoir A., Lavialle C., Heidmann T. From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta, 2012, vol. 33, no. 9, pp. 663–671. doi: 10.1016/j.placenta.2012.05.005
  35. Frappier L. Epstein–Barr virus is an agent of genomic instability. Nature, 2023, vol. 616, no. 7957, pp. 441–442. doi: 10.1038/d41586-023-00936-y
  36. Freeman B., White T., Kaul T., Stow E.C., Baddoo M., Ungerleider N., Morales M., Yang H., Deharo D., Deininger P., Belancio V.P. Analysis of epigenetic features characteristic of L1 loci expressed in human cells. Nucleic Acids. Res., 2022, vol. 50, no. 4, pp. 1888–1907. doi: 10.1093/nar/gkac013
  37. Gaggar A., Coeshott C., Apelian D., Rodell T., Armstrong B.R., Shen G., Subramanian G.M., McHutchison J.G. Safety, tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific therapeutic vaccine, in healthy subjects: a randomized study. Vaccine, 2014, vol. 32. no. 39, pp. 4925–4931. doi: 10.1016/j.vaccine.2014.07.027
  38. Galindo R., Kaplan M.H., Leissner P., Verjat T., Ferlenghi I., Bagnoli F., Giusti F., Dosik M.H., Hayes D.F., Gitlin S.D., Markovitz D.M. Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer. J. Virol., 2008, vol. 82, no. 19, pp. 9329–9336. doi: 10.1128/JVI.00646-08
  39. Gianesin K., Noguera-Julian A., Zanchetta M., Del Bianco P., Petrara M.R., Freguja R., Rampon O., Fortuny C., Camós M., Mozzo E., Giaquinto C., De Rossi A. Premature aging and immune senescence in HIV-infected children. AIDS, 2016, vol. 30, no. 9, pp. 1363–1373. doi: 10.1097/QAD.0000000000001093
  40. Gioia U., Francia S., Cabrini M., Brambillasca S., Michelini F., Jones-Weinert C.W., d’Adda di Fagagna F. Pharmacological boost of DNA damage response and repair by enhanced biogenesis of DNA damage response RNAs. Sci. Rep., 2019, vol. 9, no. 1: 6460. doi: 10.1038/s41598-019-42892-6
  41. Gorbunova V., Seluanov A., Mita P., McKerrow W., Fenyö D., Boeke J.D., Linker S.B., Gage F.H., Kreiling J.A., Petrashen A.P., Woodham T.A., Taylor J.R., Helfand S.L., Sedivy J.M. The role of retrotransposable elements in ageing and age-associated diseases. Nature, 2021, vol. 596, no. 7870, pp. 43–53. doi: 10.1038/s41586-021-03542-y
  42. Grow E.J., Flynn R.A., Chavez S.L., Bayless N.L., Wossidlo M., Wesche D.J., Martin L., Ware C.B., Blish C.A., Chang H.Y., Pera R.A., Wysocka J. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells. Nature, 2015, vol. 522, no. 7555, pp. 221–225. doi: 10.1038/nature14308
  43. Guo J., Huang X., Dou L., Yan M., Shen T., Tang W., Li J. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct. Target Ther., 2022, vol. 7, no. 1: 391. doi: 10.1038/s41392-022-01251-0
  44. Guo L., Liu X., Su X. The role of TEMRA cell-mediated immune senescence in the development and treatment of HIV disease. Front. Immunol., 2023, vol. 14: 1284293. doi: 10.3389/fimmu.2023.1284293
  45. Gutiérrez-Sevilla J.E., Cárdenas-Bedoya J., Escoto-Delgadillo M., Zúñiga-González G.M., Pérez-Ríos A.M., Gómez-Meda B.C., González-Enríquez G.V., Figarola-Centurión I., Chavarría-Avila E., Torres-Mendoza B.M. Genomic instability in people living with HIV. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2021, vol. 865: 503336. doi: 10.1016/j.mrgentox.2021.503336
  46. Hancks D.C., Kazazian H.H. Jr. Roles for retrotransposon insertions in human disease. Mob. DNA, 2016, vol. 7, no. 1: 9. doi: 10.1186/s13100-016-0065-9
  47. He J., Fu X., Zhang M., He F., Li W., Abdul M.M., Zhou J., Sun L., Chang C., Li Y., Liu H., Wu K., Babarinde I.A., Zhuang Q., Loh Y.H., Chen J., Esteban M.A., Hutchins A.P. Transposable elements are regulated by context-specific patterns of chromatin marks in mouse embryonic stem cells. Nat. Commun., 2019, vol. 10, no. 1: 34. doi: 10.1038/s41467-018-08006-y
  48. Heneka M.T. An immune-cell signature marks the brain in Alzheimer’s disease. Nature, 2020, vol. 577, no. 7790, pp. 322–323. doi: 10.1038/d41586-019-03892-8
  49. Hofstee M.I., Cevirgel A., de Zeeuw-Brouwer M.L., de Rond L., van der Klis F., Buisman A.M. Cytomegalovirus and Epstein–Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype. Sci. Rep., 2023, vol. 13, no. 1, pp. 10912 doi: 10.1038/s41598-023-37502-5
  50. Hu X., Karthigeyan K.P., Herbek S., Valencia S.M., Jenks J.A., Webster H., Miller I.G., Connors M., Pollara J., Andy C., Gerber L.M., Walter E.B., Edwards K.M., Bernstein D.I., Hou J., Koch M., Panther L., Carfi A., Wu K., Permar S.R. Human cytomegalovirus mRNA-1647 vaccine candidate elicits potent and broad neutralization and higher antibody-dependent cellular cytotoxicity responses than the gB/MF59 vaccine. J. Infect. Dis., 2024, vol. 230, no. 2, pp. 455–466. doi: 10.1093/infdis/jiad593
  51. Huang R., Chen Z., Dolan S., Schetz J.A, Dillon G.H. The dual modulatory effects of efavirenz on GABAA receptors are mediated via two distinct sites. Neuropharmacology, 2017, vol. 121, pp. 167–178. doi: 10.1016/j.neuropharm.2017.04.038
  52. Hurme M. Viruses and immunosenescence — more players in the game. Immun. Ageing, 2019, vol. 16, no. 1: 13. doi: 10.1186/s12979-019-0152-0
  53. Jin L., He J., Feng H., Li S., Liu H., Dong H., Hu M., Huang J., Wu H., Chen J., Qi L., Wu K. Transposable elements activation triggers necroptosis in mouse embryonic stem cells. Cell. Death. Dis., 2023, vol. 14, no. 3: 184. doi: 10.1038/s41419-023-05705-3
  54. Jin Y., Liu X., Liang X., Liu J., Liu J., Han Z., Lu Q., Wang K., Meng B., Zhang C., Xu M., Guan J., Ma L., Zhou L. Resveratrol rescues cutaneous radiation-induced DNA damage via a novel AMPK/SIRT7/HMGB1 regulatory axis. Cell. Death. Dis., 2023, vol. 13, no. 10: 847. doi: 10.1038/s41419-022-05281-y
  55. Johanning G.L., Malouf G.G., Zheng X., Esteva F.J., Weinstein J.N., Wang-Johanning F., Su X. Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype. Sci. Rep., 2017, vol. 7, no. 1: 41960. doi: 10.1038/srep41960
  56. Johnson L.B., Saravolatz L.D. Etravirine, a next-generation nonnucleoside reverse-transcriptase inhibitor. Clin. Infect. Dis., 2009, vol. 48, no. 8, pp. 1123–1128. doi: 10.1086/597469
  57. Justice J.N., Nambiar A.M., Tchkonia T., LeBrasseur N.K., Pascual R., Hashmi S.K., Prata L., Masternak M.M., Kritchevsky S.B., Musi N., Kirkland J.L. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine, 2019, vol. 40, pp. 554–563. doi: 10.1016/j.ebiom.2018.12.052
  58. Kanfi Y., Naiman S., Amir G., Peshti V., Zinman G., Nahum L., Bar-Joseph Z., Cohen H.Y. The sirtuin SIRT6 regulates lifespan in male mice. Nature, 2012, vol. 483, no. 7388, pp. 218–221. doi: 10.1038/nature10815
  59. Kang Q., Guo X., Li T., Yang C., Han J., Jia L., Liu Y., Wang X., Zhang B., Li J., Wen H.L., Li H., Li L. Identification of differentially expressed HERV-K(HML-2) loci in colorectal cancer. Front. Microbiol., 2023, vol. 14: 1192900. doi: 10.3389/fmicb.2023
  60. Kho Z.Y., Lal S.K. The human gut microbiome — a potential controller of wellness and disease. Front. Microbiol., 2018, vol. 9: 1835. doi: 10.3389/fmicb.2018.01835
  61. Kim K.M., Noh J.H., Bodogai M., Martindale J.L., Yang X., Indig F.E., Basu S.K., Ohnuma K., Morimoto C., Johnson P.F., Biragyn A., Abdelmohsen K., Gorospe M. Identification of senescent cell surface targetable protein DPP4. Genes Dev., 2017, vol. 31, no. 15, pp. 1529–1534. doi: 10.1101/gad.302570.117
  62. Kontorinis N., Dieterich D.T. Toxicity of non-nucleoside analogue reverse transcriptase inhibitors. Semin. Liver Dis., 2003, vol. 23, no. 2, pp. 173–182. doi: 10.1055/s-2003-39948
  63. Kulpa D.A., Moran J.V. Cis-preferential LINE-1 reverse transcriptase activity in ribonucleoprotein particles. Nat. Struct. Mol. Biol., 2006, vol. 13, no. 7, pp. 655–660. doi: 10.1038/nsmb1107
  64. Kuriyama Y., Shimizu A., Kanai S., Oikawa D., Motegi S.I., Tokunaga F., Ishikawa O. Coordination of retrotransposons and type I interferon with distinct interferon pathways in dermatomyositis, systemic lupus erythematosus and autoimmune blistering disease. Sci. Rep., 2021, vol. 11, no. 1: 23146. doi: 10.1038/s41598-021-02522-6
  65. Lacey D., Hickey P., Arhatari B.D., O’Reilly L.A., Rohrbeck L., Kiriazis H., Du X.J., Bouillet P. Spontaneous retrotransposon insertion into TNF 3'UTR causes heart valve disease and chronic polyarthritis. Proc. Natl Acad. Sci. USA, 2015, vol. 112, no. 31, pp. 9698–9703. doi: 10.1073/pnas.1508399112
  66. Larbi A., Pawelec G., Witkowski J.M., Schipper H.M., Derhovanessian E., Goldeck D., Fulop T. Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer’s disease. J. Alzheimers Dis., 2009, vol. 17, no. 1. pp. 91–103. doi: 10.3233/JAD-2009-1015
  67. Lelarge V., Capelle R., Oger F., Mathieu T., Le Calvé B. Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment. NPJ Aging, 2024, vol. 10, no. 1: 12. doi: 10.1038/s41514-024-00138-4
  68. Li W., Pandya D., Pasternack N., Garcia-Montojo M., Henderson L., Kozak C.A., Nath A. Retroviral Elements in pathophysiology and as therapeutic targets for amyotrophic lateral sclerosis. Neurotherapeutics, 2022, vol. 19, no. 4, pp. 1085–1101. doi: 10.1007/s13311-022-01233-8
  69. Li X., Li C., Zhang W., Wang Y., Qian P., Huang H. Inflammation and aging: signaling pathways and intervention therapies. Signal. Transduct. Target. Ther., 2023, vol. 8, no. 1: 239. doi: 10.1038/s41392-023-01502-8
  70. Li X., Yu H., Li D., Liu N. LINE-1 transposable element renaissance in aging and age-related diseases. Ageing Res. Rev., 2024, vol. 100: 102440. doi: 10.1016/j.arr.2024.102440
  71. Li Y., Chen Y., Zhang N., Fan D. Human endogenous retrovirus K (HERV-K) env in neuronal extracellular vesicles: a new biomarker of motor neuron disease. Amyotroph. Lateral Scler. Frontotemporal Degener., 2022, vol. 23, no. 1–2, pp. 100–107. doi: 10.1080/ 21678421.2021.1936061
  72. Liang C., Ke Q., Liu Z., Ren J., Zhang W., Hu J., Wang Z., Chen H., Xia K., Lai X., Wang Q., Yang K., Li W., Wu Z., Wang C., Yan H., Jiang X., Ji Z., Ma M., Long X., Wang S., Wang H., Sun H., Belmonte J.C.I., Qu J., Xiang A.P., Liu G.H. BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates. Nucleic Acids Res., 2022, vol. 50, no. 6, pp. 3323–3347. doi: 10.1093/nar/gkac146
  73. Liu H., Xu Q., Wufuer H., Li Z., Sun R., Jiang Z., Dou X., Fu Q., Campisi J., Sun Y. Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy. Aging Cell, 2024, vol. 23, no. 1: e13921 doi: 10.1111/acel.14183
  74. Liu X., Liu Z., Wu Z., Ren J., Fan Y., Sun L., Cao G., Niu Y., Zhang B., Ji Q., Jiang X., Wang C., Wang Q., Ji Z., Li L., Esteban C.R., Yan K., Li W., Cai Y., Wang S., Zheng A., Zhang Y.E., Tan S., Cai Y., Song M., Lu F., Tang F., Ji W., Zhou Q., Belmonte J.C.I., Zhang W., Qu J., Liu G.H. Resurrection of endogenous retroviruses during aging reinforces senescence. Cell, 2023, vol. 186, no. 2, pp. 287–304.e26. doi: 10.1016/j.cell.2022.12.017
  75. López-Gil L., Pascual-Ahuir A., Proft M. Genomic instability and epigenetic changes during aging. Int. J. Mol. Sci., 2023, vol. 24, no. 18: 14279. doi: 10.3390/ijms241814279
  76. Martínez E., Blanco J.L., Arnaiz J.A., Pérez-Cuevas J.B., Mocroft A., Cruceta A., Marcos M.A., Milinkovic A., García-Viejo M.A., Mallolas J., Carné X., Phillips A., Gatell J.M. Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy. AIDS, 2001, vol. 15, no. 10, pp. 1261–1268. doi: 10.1097/00002030-200107060-00007
  77. Martyshkina Y.S., Tereshchenko V.P., Bogdanova D.A., Rybtsov S.A. Reliable hallmarks and biomarkers of senescent lymphocytes. Int. J. Mol. Sci., 2023, vol. 24, no. 21: 15653. doi: 10.3390/ijms242115653
  78. Matveeva K., Vasilieva M., Minskaia E., Rybtsov S. Shevyrev, D. T-cell immunity against senescence: potential role and perspectives. Front. Immunol., 2024, vol. 15: 1360109. doi: 10.3389/fimmu.2024.1360109
  79. Merchut-Maya J.M., Bartek J. Jr., Bartkova J., Galanos P., Pantalone M.R., Lee M., Cui H.L., Shilling P.J., Brøchner C.B., Broholm H., Maya-Mendoza A., Söderberg-Naucler C., Bartek J. Human cytomegalovirus hijacks host stress response fueling replication stress and genome instability. Cell. Death Differ., 2022, vol. 29, no. 8, pp. 1639–1653. doi: 10.1038/s41418-022-00953-w
  80. Mislak A.C., Frey K.M., Bollini M., Jorgensen W.L., Anderson K.S. A Mechanistic and Structural Investigation of Modified Derivatives of the Diaryltriazine Class of NNRTIs Targeting HIV-1 Reverse Transcriptase. Biochim. Biophys. Acta, 2014, vol. 1840, no. 7, pp. 2203–2211. doi: 10.1016/j.bbagen.2014.04.0010
  81. Mutlib A.E., Gerson R.J., Meunier P.C., Haley P.J., Chen H., Gan L.S., Davies M.H., Gemzik B., Christ D.D., Krahn D.F., Markwalder J.A., Seitz S.P., Robertson R.T., Miwa G.T. The species-dependent metabolism of efavirenz produces a nephrotoxic glutathione conjugate in rats. Toxicol. Appl. Pharmacol., 2000, vol. 169, no. 1, pp. 102–113. doi: 10.1006/taap.2000.9055
  82. Mitchell M.L., Son J.C., Guo H., Im Y.A., Cho E.J., Wang J., Hayes J., Wang M., Paul A., Lansdon E.B., Chen J.M., Graupe D., Rhodes G., He G.X., Geleziunas R., Xu L., Kim C.U. N1-Alkyl pyrimidinediones as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett., 2010, vol. 20, no. 5, pp. 1589–1592. doi: 10.1016/j.bmcl.2010.01.085
  83. Neidhart M., Rethage J., Kuchen S., Künzler P., Crowl R.M., Billingham M.E., Gay R.E., Gay S. Retrotransposable L1 elements expressed in rheumatoid arthritis synovial tissue: association with genomic DNA hypomethylation and influence on gene expression. Arthritis Rheum., 2000, vol. 43, no. 12, pp. 2634–2647. doi: 10.1002/1529-0131(200012)43:12<2634::AID-ANR3>3.0.CO;2-1
  84. Ng K.W., Boumelha J., Enfield K.S.S., Almagro J., Cha H., Pich O., Karasaki T., Moore D.A., Salgado R., Sivakumar M., Young G., Molina-Arcas M., de Carné Trécesson S., Anastasiou P., Fendler A., Au L., Shepherd S.T.C., Martínez-Ruiz C., Puttick C., Black J.R.M., Watkins T.B.K., Kim H., Shim S., Faulkner N., Attig J., Veeriah S., Magno N., Ward S., Frankell A.M., Al Bakir M., Lim E.L., Hill M.S., Wilson G.A., Cook D.E., Birkbak N.J., Behrens A., Yousaf N., Popat S., Hackshaw A.; TRACERx Consortium; CAPTURE Consortium; Hiley C.T., Litchfield K., McGranahan N., Jamal-Hanjani M., Larkin J., Lee S.H., Turajlic S., Swanton C., Downward J., Kassiotis G. Antibodies against endogenous retroviruses promote lung cancer immunotherapy. Nature, 2023, vol. 616, no. 7957, pp. 563–573. doi: 10.1038/s41586-023-05771-9
  85. Niedernhofer L.J., Gurkar A.U., Wang Y., Vijg J., Hoeijmakers J.H.J., Robbins P.D. Nuclear Genomic Instability and Aging. Annu. Rev. Biochem., 2018, vol. 87, no. 1, pp. 295–322. doi: 10.1146/annurev-biochem-062917-012239
  86. Odama M., Maegawa E., Suzuki K., Fujii Y., Maeda R., Murakami S., Ito T. Effects of betulinic acid on the proliferation, cellular senescence, and type 1 interferon-related signaling pathways in human dermal fibroblasts. J. Agric. Food. Chem., 2023, vol. 71, no. 18, pp. 6935–6943. doi: 10.1021/acs.jafc.2c08563
  87. O’Donnell J.S., Hunt S.K., Chappell K.J. Integrated molecular and immunological features of human T-lymphotropic virus type 1 infection and disease progression to adult T-cell leukaemia or lymphoma. Lancet Haematol., 2023, vol. 10, no. 7, pp. e539–e548. doi: 10.1016/S2352-3026(23)00087-X
  88. Ostrowski L.A., Hall A.C., Szafranski K.J., Oshidari R., Abraham K.J., Chan J.N.Y., Krustev C., Zhang K., Wang A., Liu Y., Guo R., Mekhail K. Conserved Pbp1/Ataxin-2 regulates retrotransposon activity and connects polyglutamine expansion-driven protein aggregation to lifespan-controlling rDNA repeats. Commun. Biol., 2018, vol. 1, no. 1: 187. doi: 10.1038/s42003-018-0187-3
  89. Pastuzyn E.D., Day C.E., Kearns R.B., Kyrke-Smith M., Taibi A.V., McCormick J., Yoder N., Belnap D.M., Erlendsson S., Morado D.R., Briggs J.A.G., Feschotte C., Shepherd J.D. The neuronal gene arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer. Cell, 2018, vol. 172, no. 1–2, pp. 275–288. doi: 10.1016/j.cell.2017.12.024
  90. Pau A.K., George J.M. Antiretroviral therapy: current drugs. Infect. Dis. Clin. North Am., 2014, vol. 28, no. 3, pp. 371–402. doi: 10.1016/j.idc.2014.06.001
  91. Pawelec G. Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun. Ageing, 2012, vol. 9, no. 1: 15. doi: 10.1186/1742-4933-9-15
  92. Peng Y., Zong Y., Wang D., Chen J., Chen Z.S., Peng F., Liu Z. Current drugs for HIV-1: from challenges to potential in HIV/AIDS. Front. Pharmacol., 2023, vol. 14: 1294966. doi: 10.3389/fphar.2023.1294966
  93. Pessoa J., Nóbrega-Pereira S., de Jesus B.B. Senescent cell-derived vaccines: a new concept towards an immune response against cancer and aging? Aging (Albany NY), 2024, vol. 16, no. 12, pp. 10657–10665. doi: 10.18632/aging.205975
  94. Petr M.A., Tulika T., Carmona-Marin L.M., Scheibye-Knudsen M. Protecting the aging genome. Trends. Cell. Biol., 2020, vol. 30, no. 2, pp. 117–132. doi: 1016/j.tcb.2019.12.00110
  95. Phan J., Chen B., Zhao Z., Allies G., Iannaccone A., Paul A., Cansiz F., Spina A., Leven A.S., Gellhaus A., Schadendorf D., Kimmig R., Mettlen M., Tasdogan A., Morrison S.J. Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis. Science, 2024, vol. 386, no. 6722: eado6836. doi: 10.1126/science.ado6836
  96. Pich O., Reyes-Salazar I., Gonzalez-Perez A., Lopez-Bigas N. Discovering the drivers of clonal hematopoiesis. Nat. Commun., 2022, vol. 13, no. 1: 4267. doi: 10.1038/s41467-022-31878-0
  97. Pilié P.G., Tang C., Mills G.B., Yap T.A. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat. Rev. Clin. Oncol., 2019, vol. 16, no. 2, pp. 81–104. doi: 10.1038/s41571-018-0114-z
  98. Pradhan R.K., Ramakrishna W. Transposons: Unexpected players in cancer. Gene, 2022, vol. 808: 145975. doi: 10.1016/j.gene.2021.145975
  99. Prati B., Marangoni B., Boccardo E. Human papillomavirus and genome instability: from productive infection to cancer. Clinics (Sao Paulo), 2018, vol. 73: e539s. doi: 10.6061/clinics/2018/e539s
  100. Pukhalskaia T.V., Yurakova T.R., Bogdanova D.A., Demidov O.N. Tumor-associated senescent macrophages, their markers, and their role in tumor microenvironment. Biochemistry (Mosc.), 2024, vol. 89, no. 5, pp. 839–852. doi: 10.1134/S0006297924050055
  101. Raviola S., Griffante G., Iannucci A., Chandel S., Lo Cigno I., Lacarbonara D., Caneparo V., Pasquero S., Favero F., Corà D., Trisolini E., Boldorini R., Cantaluppi V., Landolfo S., Gariglio M., De Andrea M. Human cytomegalovirus infection triggers a paracrine senescence loop in renal epithelial cells. Commun. Biol., 2024, vol. 7, no. 1: 292. doi: 10.1038/s42003-024-05957-5
  102. Reis B.S., Jungbluth A.A., Frosina D., Holz M., Ritter E., Nakayama E., Ishida T., Obata Y., Carver B., Scher H., Scardino P.T., Slovin S., Subudhi S.K., Reuter V.E., Savage C., Allison J.P., Melamed J., Jäger E., Ritter G., Old L.J., Gnjatic S. Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein. Clin. Cancer Res., 2013, vol. 19, no. 22, pp. 6112–6125. doi: 10.1158/1078-0432.CCR-12-3580
  103. Reyes A., Ortiz G., Duarte L.F., Fernández C., Hernández-Armengol R., Palacios P.A., Prado Y., Andrade C.A., Rodriguez-Guilarte L., Kalergis A.M., Simon F., Carreño L.J., Riedel C.A., Cáceres M., González P.A. Contribution of viral and bacterial infections to senescence and immunosenescence. Front. Cell. Infect. Microbiol., 2023, vol. 13: 1229098. doi: 10.3389/fcimb.2023.1229098
  104. Riaz Rajoka M.S., Zhao H., Li N., Lu Y., Lian Z., Shao D., Jin M., Li Q., Zhao L., Shi J. Origination, change, and modulation of geriatric disease-related gut microbiota during life. Appl Microbiol. Biotechnol., 2018, vol. 102, no. 19, pp. 8275–8289. doi: 10.1007/s00253-018-9264-2
  105. Rivas S.R., Valdez M.J.M., Govindarajan V., Seetharam D., Doucet-O’Hare T.T., Heiss J.D., Shah A.H. The role of HERV-K in cancer stemness. Viruses, 2022, vol. 14, no. 9: 2019. doi: 10.3390/v14092019
  106. Robinson W.H, Steinman L. Epstein–Barr virus and multiple sclerosis. Science, 2022, vol. 375, no. 6578, pp. 264–265. doi: 10.1126/science.abm7930
  107. Rodić N., Sharma R., Sharma R., Zampella J., Dai L., Taylor M.S., Hruban R.H., Iacobuzio-Donahue C.A., Maitra A., Torbenson M.S., Goggins M., Shih IeM., Duffield A.S., Montgomery E.A., Gabrielson E., Netto G.J., Lotan T.L., De Marzo A.M., Westra W., Binder Z.A., Orr B.A., Gallia G.L., Eberhart C.G., Boeke J.D., Harris C.R., Burns K.H. Long interspersed element-1 protein expression is a hallmark of many human cancers. Am. J. Pathol., 2014, vol. 184, no. 5, pp. 1280–1286. doi: 10.1016/j.ajpath.2014.01.007
  108. Ross J.B., Myers L.M., Noh J.J., Collins M.M., Carmody A.B., Messer R.J., Dhuey E., Hasenkrug K.J., Weissman I.L. Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity. Nature, 2024, vol. 628, no. 8006, pp. 162–170. doi: 10.1038/s41586-024-07238-x
  109. Rowe H.M., Kapopoulou A., Corsinotti A., Fasching L., Macfarlan T.S., Tarabay Y., Viville S., Jakobsson J., Pfaff S.L., Trono D. TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells. Genome Res., 2013, vol. 23, no. 3, pp. 452–461. doi: 10.1101/gr.147678.112
  110. Rybtsova N., Berezina T.N., Rybtsov S. Molecular markers of blood cell populations can help estimate aging of the immune system. Int. J. Mol. Sci., 2023, vol. 24, no. 6: 5708. doi: 10.3390/ijms24065708
  111. Sagiv A., Burton D.G., Moshayev Z., Vadai E., Wensveen F., Ben-Dor S., Golani O., Polic B., Krizhanovsky V. NKG2D ligands mediate immunosurveillance of senescent cells. Aging (Albany NY), 2016, vol. 8, no. 2, pp. 328–344. doi: 10.18632/aging.100897
  112. Sbardella G., Bartolini S., Castellano S., Artico M., Paesano N., Rotili D., Spadafora C., Mai A. 6-alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs): novel regulators of cell differentiation and proliferation. ChemMedChem., 2006, vol. 1, no. 10, pp. 1073–1080. doi: 10.1002/cmdc.200600139
  113. Sbardella G., Mai A., Bartolini S., Castellano S., Cirilli R., Rotili D., Milite C., Santoriello M., Orlando S., Sciamanna I., Serafino A., Lavia P., Spadafora C. Modulation of cell differentiation, proliferation, and tumor growth by dihydrobenzyloxopyrimidine non-nucleoside reverse transcriptase inhibitors. J. Med. Chem., 2011, vol. 54, no. 16, pp. 5927–5936. doi: 10.1021/jm200734j
  114. Schoepf I.C., Esteban-Cantos A., Thorball C.W., Rodés B., Reiss P., Rodríguez-Centeno J., Riebensahm C., Braun D.L., Marzolini C., Seneghini M., Bernasconi E., Cavassini M., Buvelot H., Thurnheer M.C., Kouyos R.D., Fellay J., Günthard H.F., Arribas J.R., Ledergerber B., Tarr P.E. Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years. Lancet. Healthy. Longev., 2023, vol. 4, no. 5, pp. e211–e218. doi: 10.1016/S2666-7568(23)00037-5
  115. Sciamanna I., Landriscina M., Pittoggi C., Quirino M., Mearelli C., Beraldi R., Mattei E., Serafino A., Cassano A., Sinibaldi-Vallebona P., Garaci E., Barone C., Spadafora C. Inhibition of endogenous reverse transcriptase antagonizes human tumor growth. Oncogene, 2005, vol. 24, no. 24, pp. 3923–3931. doi: 10.1038/sj.onc.1208562
  116. Sciamanna I., Vitullo P., Curatolo A., Spadafora C. A reverse transcriptase-dependent mechanism is essential for murine preimplantation development. Genes (Basel), 2011, vol. 2, no. 2, pp. 360–373. doi: 10.3390/genes2020360
  117. Sharma A.M., Li Y., Novalen M., Hayes M.A., Uetrecht J. Bioactivation of nevirapine to a reactive quinone methide: implications for liver injury. Chem. Res. Toxicol., 2012, vol. 25, no. 8, pp. 1708–1719. doi: 10.1021/tx300172s
  118. Shevyrev D., Tereshchenko V., Berezina T.N., Rybtsov S. Hematopoietic stem cells and the immune system in development and aging. Int. J. Mol. Sci., 2023, vol. 24, no. 6: 5862. doi: 10.3390/ijms24065862
  119. Simon M., Van Meter M., Ablaeva J., Ke Z., Gonzalez R.S., Taguchi T., De Cecco M., Leonova K.I., Kogan V., Helfand S.L., Neretti N., Roichman A., Cohen H.Y., Meer M.V., Gladyshev V.N., Antoch M.P., Gudkov A.V., Sedivy J.M., Seluanov A., Gorbunova V. LINE1 derepression in aged wild-type and SIRT6-deficient mice drives inflammation. Cell Metab., 2019, vol. 29, no. 4, pp. 871–885. doi: 10.1016/j.cmet.2019.02.014
  120. Singh M., Cai H., Bunse M., Feschotte C., Izsvák Z. Human Endogenous Retrovirus K Rec forms a regulatory loop with MITF that opposes the progression of melanoma to an invasive stage. Viruses, 2020, vol. 12, no. 11: 1303. doi: 10.3390/v12111303
  121. Smer-Barreto V., Quintanilla A., Elliott R.J.R., Dawson J.C., Sun J., Campa V.M., Lorente-Macías Á., Unciti-Broceta A., Carragher N.O., Acosta J.C., Oyarzún D.A. Discovery of senolytics using machine learning. Nat. Commun., 2023, vol. 14, no. 1: 3445. doi: 10.1038/s41467-023-39120-1
  122. Solana R., Tarazona R., Aiello A.E., Akbar A.N., Appay V., Beswick M., Bosch J.A., Campos C., Cantisán S., Cicin-Sain L., Derhovanessian E., Ferrando-Martínez S., Frasca D., Fulöp T., Govind S., Grubeck-Loebenstein B., Hill A., Hurme M., Kern F., Larbi A., López-Botet M., Maier A.B., McElhaney J.E., Moss P., Naumova E., Nikolich-Zugich J., Pera A., Rector J.L., Riddell N., Sanchez-Correa B., Sansoni P., Sauce D., van Lier R., Wang G.C., Wills M.R., Zieliński M., Pawelec G. CMV and Immunosenescence: from basics to clinics. Immun. Ageing, 2012, vol. 9, no. 1: 23. doi: 10.1186/1742-4933-9-23
  123. Song D.G., Ye Q., Santoro S., Fang C., Best A., Powell D.J. Jr. Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition. Hum. Gene Ther., 2013, vol. 24, no. 3, pp. 295–305. doi: 10.1089/hum.2012.143
  124. Spadafora C. A LINE-1-encoded reverse transcriptase-dependent regulatory mechanism is active in embryogenesis and tumorigenesis. Ann. N.Y. Acad. Sci., 2015, vol., 1341, no. 1, pp. 164–171. doi: 10.1111/nyas.12637
  125. Stoeger T., Grant R.A., McQuattie-Pimentel A.C., Anekalla K.R., Liu S.S., Tejedor-Navarro H., Singer B.D., Abdala-Valencia H., Schwake M., Tetreault M.P., Perlman H., Balch W.E., Chandel N.S., Ridge K.M., Sznajder J.I., Morimoto R.I., Misharin A.V., Budinger G.R.S., Nunes Amaral L.A. Aging is associated with a systemic length-associated transcriptome imbalance. Nat. Aging, 2022, vol. 2, no. 12, pp. 1191–1206. doi: 10.1038/s43587-022-00317-6
  126. Su B., Gao G., Wang M., Lu Y., Li L., Chen C., Chen Y., Song C., Yu F., Li Y., Liu Y., Luo Y., He H., Cheng C., Xu L., Zhang T., Sun L., Liu A., Xia W., Qin Y., Zhao Q., Wei H., Cai W., Chen Y., Zhang F., Wu H. Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96. Lancet Reg. Health West Pac., 2023, vol. 36: 100769. doi: 10.1016/j.lanwpc.2023.100769
  127. Sun J.X., Xu J.Z., Liu C.Q., An Y., Xu M.Y., Zhong X.Y., Zeng N., Ma S.Y., He H.D., Hu J., Liu Z., Wang S.G., Xia Q.D. The association between human papillomavirus and bladder cancer: Evidence from meta-analysis and two-sample mendelian randomization. J. Med. Virol., 2023, vol. 95, no. 1: e28208 doi: 10.1002/jmv.28208
  128. Taglialegna, A. A virus hastens ageing in flies. Nat. Rev. Microbiol., 2024, vol. 22, no. 8, pp. 455–455. doi: 10.1038/s41579-024-01070-w
  129. Ukadike K.C., Najjar R., Ni K., Laine A., Wang X., Bays A., Taylor M.S., LaCava J., Mustelin T. Expression of L1 retrotransposons in granulocytes from patients with active systemic lupus erythematosus. Mob. DNA, 2023, vol. 14, no. 1: 5. doi: 10.1186/s13100-023-00293-7
  130. Vijg J., Montagna C. Genome instability and aging: Cause or effect? Translational Medicine of Aging, 2017, vol. 1, pp. 5–11. doi: 10.33029/1816-2134-2024-45-2-221-234
  131. Voronina M.V., Frolova A.S., Kolesova E. The intricate balance between life and death: ROS, cathepsins, and their interplay in cell death and autophagy. Int. J. Mol. Sci., 2024, vol. 25, no. 7: 4087. doi: 10.3390/ijms25074087
  132. Wahl D., Smith M.E., McEntee C.M., Cavalier A.N., Osburn S.C., Burke S.D., Grant R.A., Nerguizian D., Lark D.S., Link C.D., LaRocca T.J. The reverse transcriptase inhibitor 3TC protects against age-related cognitive dysfunction. Aging Cell, 2023, vol. 22, no. 5: e13798. doi: 10.1111/acel.13798
  133. Wang T., Medynets M., Johnson K.R., Doucet-O’Hare T.T., DiSanza B., Li W., Xu Y., Bagnell A., Tyagi R., Sampson K., Malik N., Steiner J., Hadegan A., Kowalak J., O’Malley J., Maric D., Nath A. Regulation of stem cell function and neuronal differentiation by HERV-K via mTOR pathway. Proc. Natl Acad. Sci. USA, 2020, vol. 117, no. 30, pp. 17842–17853. doi: 10.1073/pnas.2002427117
  134. Wells J.N., Chang N.C., McCormick J., Coleman C., Ramos N., Jin B., Feschotte C. Transposable elements drive the evolution of metazoan zinc finger genes. Genome Res., 2023, vol. 33, no. 8, pp. 1325–1339. doi: 10.1101/gr.277966.123
  135. Wilmoth J.R. Demography of longevity: past, present, and future trends. Exp. Gerontol., 2000, vol. 35, no. 9–10, pp. 1111–1129. doi: 10.1016/s0531-5565(00)00194-7
  136. Wit F.W.N.M., Lange J.M.A., Volberding P.A. New HIV drug development. HIV/AIDS Medicine, 2008, pp. 123–134. doi: 10.1016/B978-1-4160-2882-6.50016-2
  137. Wong Y., Meehan M.T., Burrows S.R., Doolan D.L., Miles J.J. Estimating the global burden of Epstein–Barr virus-related cancers. J. Cancer Res. Clin. Oncol., 2022, vol. 148, no. 1, pp. 31–46. doi: 10.1007/s00432-021-03824-y
  138. Wu J., Wu C., Xing F., Cao L., Zeng W., Guo L., Li P., Zhong Y., Jiang H., Luo M., Shi G., Bu L., Ji Y., Hou P., Peng H., Huang J., Li C., Guo D. Endogenous reverse transcriptase and RNase H-mediated antiviral mechanism in embryonic stem cells. Cell Res., 2021, vol. 31, no. 9, pp. 998–1010. doi: 10.1038/s41422-021-00524-7
  139. Yang B., Li T., Wang Z., Zhu Y., Niu K., Hu S., Lin Z., Zheng X., Jin X., Shen C. Ruxolitinib-based senomorphic therapy mitigates cardiomyocyte senescence in septic cardiomyopathy by inhibiting the JAK2/STAT3 signaling pathway. Int. J. Biol. Sci., 2024, vol. 20, no. 11, pp. 4314–4340. doi: 10.7150/ijbs.96489
  140. Yoshida S., Nakagami H., Hayashi H., Ikeda Y., Sun J., Tenma A., Tomioka H., Kawano T., Shimamura M., Morishita R., Rakugi H. The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice. Nat. Commun., 2020, vol. 11, no. 1: 2482. doi: 10.1038/s41467-020-16347-w
  141. Zhang L., Pitcher L.E., Prahalad V., Niedernhofer L.J., Robbins P.D. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics. FEBS J., 2023, vol. 290, no. 5, pp. 1362–1383. doi: 10.1111/febs.16350
  142. Zhong L., Zhao Q., Zeng M.S., Zhang X. Prophylactic vaccines against Epstein–Barr virus. Lancet, 2024, vol. 404, no. 10455: 845. doi: 10.1016/S0140-6736(24)01608-8
  143. Zhou L., Mitra R., Atkinson P.W., Hickman A.B., Dyda F., Craig N.L. Transposition of hAT elements links transposable elements and V(D)J recombination. Nature, 2004, vol. 432, no. 7020, pp. 995–1001. doi: 10.1038/nature03157
  144. Zlotorynski E. Younger endogenous retroviruses make us older. Nat. Rev. Mol. Cell Biol., 2023, vol. 24: 165. doi: 10.1038/s41580-023-00580-4

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Lysakova E.V., Burak M.Y., Navrotsky M.B., Rybtsov S.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».