actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2026-11.1.11actabiomedica-5909Research ArticleМОРФОЛОГИЯ, ФИЗИОЛОГИЯ И ПАТОФИЗИОЛОГИЯMORPHOLOGY, PHYSIOLOGY AND PATHOPHYSIOLOGYКлеточное старение и его биомаркеры: патофизиологическое значение, молекулярные механизмы и клинические перспективыCellular senescence and senescence biomarkers: pathophysiological significance, molecular mechanisms, and clinical perspectiveshttps://orcid.org/0000-0003-1180-228XБорукаеваИ. Х.BorukaevaI. Kh.

Борукаева Ирина Хасанбиевна - доктор медицинских наук, доцент, заведующая кафедрой нормальной и патологической физиологии человека.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Irina Kh. Borukaeva - Dr. Sc. (Med.), head of the Department of Normal and Pathological Human Physiology Kabardino-Balkarian State University named after H.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

irborukaeva@yandex.ruhttps://orcid.org/0000-0003-2302-2491ХараеваЗ. Ф.KharaevaZ. F.

Хараева Заира Феликсовна - доктор медицинских наук, профессор, заведующая кафедрой микробиологии, вирусологии и иммунологии.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Zaira F. Kharaeva - Dr. Sc. (Med.), professor, head of the Department of Microbiology, Virology and Immunology of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

irafe@yandex.ruhttps://orcid.org/0000-0003-4065-989XТхабисимоваИ. К.TkhabisimovaI. K.

Тхабисимова Ирина Корнеевна - кандидат медицинских наук, доцент, заведующая кафедрой общей врачебной подготовки и медицинской реабилитации.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Irina K. Tkhabisimova - Cand. Sc. (Med.), associate professor, head of the Department of general medical training and medical rehabilitation of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

tkhabisim@mail.ruhttps://orcid.org/0000-0002-7530-7483ХадзуговА. Б.KhadzugovA. B.

Хадзугов Артур Барасбиевич - кандидат медицинских наук, доцент кафедры общей врачебной подготовки и медицинской реабилитации.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Artur B. Khadzugov - Cand. Sc. (Med.), associate professor of the Department of General medical training and medical rehabilitation of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

arturahad1976@gmail.comhttps://orcid.org/0009-0001-7152-3576УмовТ. А.UmovT. A.

Умов Тембулат Алимбекович - студент 5 курса специальности Лечебное дело.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Tembulat A. Umov - 5th year student of the General Medicine specialty of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

tembulat.umov@bk.ruhttps://orcid.org/0009-0008-4967-0589ШогеновБ. М.ShogenovB. M.

Шогенов Батырбек Мусович - студент 5 курса специальности Лечебное дело.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Batyrbek M. Shogenov - 5th year student of the General Medicine specialty of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

shogenbratka@gmail.comhttps://orcid.org/0009-0008-0714-0053КунижевА. М.KunizhevA. M.

Кунижев Ахмед Муаедович - студент 5 курса специальности Лечебное дело.

360004, Кабардино-Балкарская Республика Нальчик, ул. Чернышевского, 173

Akhmed M. Kunizhev - 5th year student of the General Medicine specialty of the Kabardino-Balkarian State University named after Kh.M. Berbekov.

Chernyshevsky St., 173, Nalchik, 360004, Kabardino-Balkarian Republic

sskept@bk.ruФГБОУ ВО «Кабардино-Балкарский государственный университет им. Х.М. Бербекова»Kabardino-Balkarian State University named after H.M. Berbekov202626032026111127138Copyright © Борукаева И.Х., Хараева З.Ф., Тхабисимова И.К., Хадзугов А.Б., Умов Т.А., Шогенов Б.М., Кунижев А.М., 20262026Борукаева И.Х., Хараева З.Ф., Тхабисимова И.К., Хадзугов А.Б., Умов Т.А., Шогенов Б.М., Кунижев А.М.Borukaeva I.K., Kharaeva Z.F., Tkhabisimova I.K., Khadzugov A.B., Umov T.A., Shogenov B.M., Kunizhev A.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/5909

Старение населения сопровождается ростом частоты возрастных заболеваний, включая онкологические, нейродегенеративные и сердечно-сосудистые патологии. Одним из ключевых механизмов этих процессов является клеточная сенесценция - необратимая остановка Деления клеток при сохранении их метаболической активности. С возрастом такие клетки накапливаются, способствуют хроническому воспалению и нарушению тканевого гомеостаза. В связи с этим особую актуальность приобретает разработка надёжных биомаркеров клеточного старения.

Цель обзора

Цель обзора. Представить обзор современных данных о клеточном старении: рассмотреть его понятие и значение в патофизиологии, ключевые молекулярные механизмы, различные типы биомаркеров сенесценции и методы их обнаружения, а также клиническое значение этих биомаркеров, трудности и перспективы их применения.

Материалы и методы

Материалы и методы. Проведён поиск и анализ отечественных и зарубежных научных источников в базах данных Pubmed, eLibrary.Ru, Scopus, Google scholar, находящихся в свободном доступе с 2011 по 2025 гг.

Результаты и их обсуждение. Представлена классификация биомаркеров клеточного старения, включающая генетические маркеры, такие как укорочение теломер; эпигенетические - изменения в метилировании молекул дезоксирибонуклеиновой кислоты и формирование специфических гетерохроматиновых очагов; белковые - повышение экспрессии ингибиторов клеточного цикла и провоспалительных молекул, секретируемых стареющими клетками; эндокринные - уровень дегидроэпиандростерона сульфата, кортизола и инсулиноподобного фактора роста первого типа; а также метаболические - активность бета-галактозидазы, накопление липофусцина и повышение концентрации активных форм кислорода. Клиническая значимость этих биомаркеров заключается в оценке биологического возраста, стратификации риска возраст-ассоциированных заболеваний и мониторинга эффективности геропротекторных и сенолитических препаратов.

Заключение

Заключение. Обоснована необходимость комплексного подхода к оценке клеточного старения, сочетающего молекулярные и метаболические показатели. Отмечены перспективы создания стандартизированной панели биомаркеров («паспорта старения») для внедрения в клиническую практику и персонализированную медицину.

Population aging is accompanied by an increasing incidence of age-related diseases, including oncological, neurodegenerative, and cardiovascular pathologies. One of the key mechanisms underlying these processes is cellular senescence - an irreversible arrest of cell division while maintaining metabolic activity. With age, such cells accumulate, contribute to chronic inflammation, and disrupt tissue homeostasis. In this context, the development of reliable biomarkers of cellular aging is becoming particularly relevant.

The aim

The aim. To provide an overview of current data on cellular senescence: consider its concept and significance in pathophysiology, key molecular mechanisms, various types of senescence biomarkers and methods for their detection, as well as the clinical significance of these biomarkers, difficulties and prospects for their application.

Materials and methods

Materials and methods. Search and analysis of domestic and international scientific sources were conducted using databases such as PubMed, eLibrary.ru, Scopus, and Google Scholar, as well as open-access resources available covering the period from 2011 to 2025.

Results and discussion

Results and discussion. This study presents a comprehensive classification of cellular aging biomarkers, encompassing genetic, epigenetic, protein, endocrine, and metabolic indicators. Genetic markers include telomere shortening, while epigenetic markers involve alterations in DNA methylation and the formation of specific heterochromatin foci. Protein biomarkers are characterized by increased expression of cell cycle inhibitors and pro-inflammatory molecules secreted by senescent cells. Endocrine markers comprise levels of dehydroepiandrosterone sulfate, cortisol, and insulin-like growth factor 1. Metabolic markers include elevated β-galactosidase activity, lipofuscin accumulation, and increased concentrations of reactive oxygen species. The clinical relevance of these biomarkers lies in their utility for assessing biological age, stratifying the risk of age-related diseases, and monitoring the efficacy of geroprotective and senolytic interventions.

Conclusion

Conclusion. The necessity of a comprehensive approach to the assessment of cellular aging is substantiated, integrating molecular, metabolic, and functional parameters. The review highlights the prospects for developing a standardized panel of biomarkers (an “aging passport”) for implementation in clinical practice and personalized medicine.

клеточное старениесенесценциябиомаркерытеломерысенесцент-ассоциированный секреторный фенотипэпигенетические часыбиологический возрастcell agingsenescencebiomarkerstelomeressenescence-associated secretory phenotypeepigenetic clockbiological ageИсследование выполнено при поддержке внутреннего гранта ФГБОУ ВО КБГУ им. Х.М. Бербекова, договор № 49, и программы развития стратегического академического лидерства «ПРИОРИТЕТ-2030».ReferencesMuthamil S, Kim HY, Jang HJ, Lyu JH, Shin UC, Go Y, et al. Biomarkers of Cellular Senescence and Aging: Current State-of-the-Art, Challenges and Future Perspectives. Adv Biol (Weinh). 2024; 8(9): e2400079. doi: 10.1002/adbi.202400079Muthamil S, Kim HY, Jang HJ, Lyu JH, Shin UC, Go Y, et al. Biomarkers of Cellular Senescence and Aging: Current State-of-the-Art, Challenges and Future Perspectives. Adv Biol (Weinh). 2024; 8(9): e2400079. doi: 10.1002/adbi.202400079Wagner KD, Wagner N. The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis. Cells. 2022; 11(12): 1966. doi: 10.3390/cells11121966Wagner KD, Wagner N. The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis. Cells. 2022; 11(12): 1966. doi: 10.3390/cells11121966Ogrodnik M. Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo. Aging Cell. 2021; 20(4): e13338. doi: 10.1111/acel.13338Ogrodnik M. Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo. Aging Cell. 2021; 20(4): e13338. doi: 10.1111/acel.13338Xiang X, Dong C, Zhou L, Liu J, Rabinowitz ZM, Zhang Y, et al. Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo. J Med Chem. 2024; 67(7): 5924-5934. doi: 10.1021/acs.jmedchem.4c00179Xiang X, Dong C, Zhou L, Liu J, Rabinowitz ZM, Zhang Y, et al. Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo. J Med Chem. 2024; 67(7): 5924-5934. doi: 10.1021/acs.jmedchem.4c00179López-Otín C, Blasco MA, Partridge L, Serrano M, Kroeamer G. Hallmarks of aging: An expanding universe. Cell. 2023; 186(2): 243-278. doi: 10.1021/10.1016/j.cell.2022.11.001López-Otín C, Blasco MA, Partridge L, Serrano M, Kroeamer G. Hallmarks of aging: An expanding universe. Cell. 2023; 186(2): 243-278. doi: 10.1021/10.1016/j.cell.2022.11.001Lu KJ, Sheu JR, Teng RD, Jayakumar T, Chung CL, Hsieh CY. Ability of Local Clearance of Senescent Cells in Ipsilateral Hemisphere to Mitigate Acute Ischemic Brain Injury in Mice. Int J Biol Sci. 2023; 19(9): 2835-2847. doi: 10.7150/ijbs.84060Lu KJ, Sheu JR, Teng RD, Jayakumar T, Chung CL, Hsieh CY. Ability of Local Clearance of Senescent Cells in Ipsilateral Hemisphere to Mitigate Acute Ischemic Brain Injury in Mice. Int J Biol Sci. 2023; 19(9): 2835-2847. doi: 10.7150/ijbs.84060Eltokhi A, Catterall WA, Gamal El-Din TM. Cell-cycle arrest at the G1/S boundary enhances transient voltage-gated ion channel expression in human and insect cells. Cell Rep Methods. 2023; 3(9): 100559. doi: 10.1016/j.crmeth.2023.100559.Eltokhi A, Catterall WA, Gamal El-Din TM. Cell-cycle arrest at the G1/S boundary enhances transient voltage-gated ion channel expression in human and insect cells. Cell Rep Methods. 2023; 3(9): 100559. doi: 10.1016/j.crmeth.2023.100559.Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. 2000; 1(1): 72-6. doi: 10.1038/35036093Shay JW, Wright WE. Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol. 2000; 1(1): 72-6. doi: 10.1038/35036093Kwon J, Bakhoum SF. The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer. Cancer Discov. 2020; 10(1): 26-39. doi: 10.1158/2159-8290.CD-19-0761Kwon J, Bakhoum SF. The Cytosolic DNA-Sensing cGAS-STING Pathway in Cancer. Cancer Discov. 2020; 10(1): 26-39. doi: 10.1158/2159-8290.CD-19-0761Zeng PH, Yin WJ. The cGAS/STING signaling pathway: a cross-talk of infection, senescence and tumors. Cell Cycle. 2023; 22(1): 38-56. doi: 10.1080/15384101.2022.2109899Zeng PH, Yin WJ. The cGAS/STING signaling pathway: a cross-talk of infection, senescence and tumors. Cell Cycle. 2023; 22(1): 38-56. doi: 10.1080/15384101.2022.2109899Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015; 349(6255): aaa5612. doi: 10.1126/science.aaa5612Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science. 2015; 349(6255): aaa5612. doi: 10.1126/science.aaa5612Huang W, Hickson LJ, Eirin A, Kirkland JL, Lerman LO. Cellular senescence: the good, the bad and the unknown. Nat Rev Nephrol. 2022; 18(10): 611-627. doi: 10.1038/s41581-022-00601-zHuang W, Hickson LJ, Eirin A, Kirkland JL, Lerman LO. Cellular senescence: the good, the bad and the unknown. Nat Rev Nephrol. 2022; 18(10): 611-627. doi: 10.1038/s41581-022-00601-zWu H, Deng C, Zheng X, Huang Y, Chen C, Gu H. Identification of a novel cellular senescence-related ln-cRNA signature for prognosis and immune response in osteosarcoma. Transl Cancer Res. 2024; 13(7): 3742-3759. doi: 10.21037/tcr-24-163Wu H, Deng C, Zheng X, Huang Y, Chen C, Gu H. Identification of a novel cellular senescence-related ln-cRNA signature for prognosis and immune response in osteosarcoma. Transl Cancer Res. 2024; 13(7): 3742-3759. doi: 10.21037/tcr-24-163Zhang L, Pitcher LE, Yousefzadeh MJ, Niedernhofer LJ, Robbins PD, Zhu Y. Cellular senescence: a key therapeutic target in aging and diseases. J Clin Invest. 2022; 132(15): e158450. doi: 10.1172/JCI158450Zhang L, Pitcher LE, Yousefzadeh MJ, Niedernhofer LJ, Robbins PD, Zhu Y. Cellular senescence: a key therapeutic target in aging and diseases. J Clin Invest. 2022; 132(15): e158450. doi: 10.1172/JCI158450Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 2022; 29: 946-960. doi: 10.1038/s41418-022-00988-zEngeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 2022; 29: 946-960. doi: 10.1038/s41418-022-00988-zLai L, Shin GY, Qiu H. The Role of Cell Cycle Regulators in Cell Survival-Dual Functions of Cyclin-Dependent Kinase 20 and p21. Int J Mol Sci. 2020; 21: 8504. doi: 10.3390/ijms21228504Lai L, Shin GY, Qiu H. The Role of Cell Cycle Regulators in Cell Survival-Dual Functions of Cyclin-Dependent Kinase 20 and p21. Int J Mol Sci. 2020; 21: 8504. doi: 10.3390/ijms21228504Han X, Lei Q, Xie J, Liu H, Li J, Zhang X, et al. Potential Regulators of the Senescence-Associated Secretory Phenotype During Senescence and Aging. J Gerontol A Biol Sci Med Sci. 2022; 77(11): 2207-2218. doi: 10.1093/gerona/glac097Han X, Lei Q, Xie J, Liu H, Li J, Zhang X, et al. Potential Regulators of the Senescence-Associated Secretory Phenotype During Senescence and Aging. J Gerontol A Biol Sci Med Sci. 2022; 77(11): 2207-2218. doi: 10.1093/gerona/glac097Schwartz RE, Conboy IM. Non-Intrinsic, Systemic Mechanisms of Cellular Senescence. Cells. 2023; 12(24): 2769. doi: 10.3390/cells12242769Schwartz RE, Conboy IM. Non-Intrinsic, Systemic Mechanisms of Cellular Senescence. Cells. 2023; 12(24): 2769. doi: 10.3390/cells12242769Loo TM, Miyata K, Tanaka Y, Takahashi A. Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer. Cancer Sci. 2020; 111(2): 304-311. doi: 10.1111/cas.14266Loo TM, Miyata K, Tanaka Y, Takahashi A. Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer. Cancer Sci. 2020; 111(2): 304-311. doi: 10.1111/cas.14266Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021; 22(2): 75-95. doi: 10.1038/s41580-020-00314-wDi Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021; 22(2): 75-95. doi: 10.1038/s41580-020-00314-wSt Sauver JL, Weston SA, Atkinson EJ, Mc Gree ME, Mielke MM, White TA, et al. Biomarkers of cellular senescence and risk of death in humans. Aging Cell. 2023; 22(12): e14006. doi: 10.1111/acel.14006St Sauver JL, Weston SA, Atkinson EJ, Mc Gree ME, Mielke MM, White TA, et al. Biomarkers of cellular senescence and risk of death in humans. Aging Cell. 2023; 22(12): e14006. doi: 10.1111/acel.14006Кириченко Т.В., Маркина Ю.В., Маркин А.М., Еремин И.И., Деев Р.В. Сенесцентные клетки: терапевтическая мишень в борьбе со старением. Восстановительные биотехнологии, профилактическая, цифровая и предиктивная медицина. 2024; 1(3): 5363. doi: 10.17116/rbpdpm2024103153Kirichenko TV, Markina YuV, Markin AM, Eremin II, Deev RV. Senescent cells: a therapeutic target in correction of aging. Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2024; 1(3): 53-63. (In Russ.). doi: 10.17116/rbpdpm2024103153Sienkiewicz M, Sroka K, Binienda A, Jurk D, Fichna J. A new face of old cells: An overview about the role of senescence and telomeres in inflammatory bowel diseases. Ageing Res Rev. 2023; 91: 102083. doi: 10.1016/j.arr.2023.102083Sienkiewicz M, Sroka K, Binienda A, Jurk D, Fichna J. A new face of old cells: An overview about the role of senescence and telomeres in inflammatory bowel diseases. Ageing Res Rev. 2023; 91: 102083. doi: 10.1016/j.arr.2023.102083Yan J, Chen S, Yi Z, Zhao R, Zhu J, Ding S, et al. The role of p21 in cellular senescence and aging-related diseases. Mol Cells. 2024; 47(11): 100113. doi: 10.1016/j.mo-cell.2024.100113Yan J, Chen S, Yi Z, Zhao R, Zhu J, Ding S, et al. The role of p21 in cellular senescence and aging-related diseases. Mol Cells. 2024; 47(11): 100113. doi: 10.1016/j.mo-cell.2024.100113Swift ML, Sell C, Azizkhan-Clifford J. DNA damage-induced degradation of Sp1 promotes cellular senescence. Geroscience. 2022; 44(2): 683-698. doi: 10.1007/s11357-021-00456-5Swift ML, Sell C, Azizkhan-Clifford J. DNA damage-induced degradation of Sp1 promotes cellular senescence. Geroscience. 2022; 44(2): 683-698. doi: 10.1007/s11357-021-00456-5Billimoria R, Bhatt P. Senescence in cancer: Advances in detection and treatment modalities. Biochem Pharmacol. 2023; 215: 115739. doi: 10.1016/j.bcp.2023.115739Billimoria R, Bhatt P. Senescence in cancer: Advances in detection and treatment modalities. Biochem Pharmacol. 2023; 215: 115739. doi: 10.1016/j.bcp.2023.115739Ya J, Bayraktutan U. Senolytics and Senomorphics Targeting p38MAPK/NF-KB Pathway Protect Endothelial Cells from Oxidative Stress-Mediated Premature Senescence. Cells. 2024; 13(15): 1292. doi: 10.3390/cells13151292Ya J, Bayraktutan U. Senolytics and Senomorphics Targeting p38MAPK/NF-KB Pathway Protect Endothelial Cells from Oxidative Stress-Mediated Premature Senescence. Cells. 2024; 13(15): 1292. doi: 10.3390/cells13151292Xiao FH, Yu Q, Deng ZL, Yang K, Ye Y, Ge MX, et al. ETS1 acts as a regulator of human healthy aging via de-creasing ribosomal activity. Sci Adv. 2022; 8(17): eabf2017. doi: 10.1126/sciadv.abf2017Xiao FH, Yu Q, Deng ZL, Yang K, Ye Y, Ge MX, et al. ETS1 acts as a regulator of human healthy aging via de-creasing ribosomal activity. Sci Adv. 2022; 8(17): eabf2017. doi: 10.1126/sciadv.abf2017Ni M, Peng W, Wang X, Li J. Role of Aging in Ulcerative Colitis Pathogenesis: A Focus on ETS1 as a Promising Biomarker. J Inflamm Res. 2025; 18: 1839-1853. doi: 10.2147/JIR.S504040Ni M, Peng W, Wang X, Li J. Role of Aging in Ulcerative Colitis Pathogenesis: A Focus on ETS1 as a Promising Biomarker. J Inflamm Res. 2025; 18: 1839-1853. doi: 10.2147/JIR.S504040Reimann M, Lee S, Schmitt CA. Cellular senescence: Neither irreversible nor reversible. J Exp Med. 2024; 221(4): e20232136. doi: 10.1084/jem.20232136Reimann M, Lee S, Schmitt CA. Cellular senescence: Neither irreversible nor reversible. J Exp Med. 2024; 221(4): e20232136. doi: 10.1084/jem.20232136Wang B, Han J, Elisseeff JH, Demaria M. The senescence-associated secretory phenotype and its physiological and pathological implications. Nat Rev Mol Cell Biol. 2024; 25(12): 958-978. doi: 10.1038/s41580-024-00727-xWang B, Han J, Elisseeff JH, Demaria M. The senescence-associated secretory phenotype and its physiological and pathological implications. Nat Rev Mol Cell Biol. 2024; 25(12): 958-978. doi: 10.1038/s41580-024-00727-xMohamad Kamal NS, Safuan S, Shamsuddin S, Foroozandeh P. Aging of the cells: Insight into cellular senescence and detection Methods. Eur J Cell Biol. 2020; 99(6): 151108. doi: 10.1016/j.ejcb.2020.151108Mohamad Kamal NS, Safuan S, Shamsuddin S, Foroozandeh P. Aging of the cells: Insight into cellular senescence and detection Methods. Eur J Cell Biol. 2020; 99(6): 151108. doi: 10.1016/j.ejcb.2020.151108Saul D, Kosinsky RL, Atkinson EJ, Doolittle ML, Zhang X, LeBrasseur NK, et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat Commun. 2022; 13(1): 4827. doi: 10.1038/s41467-022-32552-1Saul D, Kosinsky RL, Atkinson EJ, Doolittle ML, Zhang X, LeBrasseur NK, et al. A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues. Nat Commun. 2022; 13(1): 4827. doi: 10.1038/s41467-022-32552-1Huo S, Tang X, Chen W, Gan D, Guo H, Yao Q, et al. Epigenetic regulations of cellular senescence in osteoporosis. Ageing Res Rev. 2024; 99: 102235. doi: 10.1016/j.arr.2024.102235Huo S, Tang X, Chen W, Gan D, Guo H, Yao Q, et al. Epigenetic regulations of cellular senescence in osteoporosis. Ageing Res Rev. 2024; 99: 102235. doi: 10.1016/j.arr.2024.102235Ghosh M, Saha S, Li J, Montrose DC, Martinez LA. p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression. Mol Cell. 2023; 83(2): 266-280. e6. doi: 10.1016/j.molcel.2022.12.023Ghosh M, Saha S, Li J, Montrose DC, Martinez LA. p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression. Mol Cell. 2023; 83(2): 266-280. e6. doi: 10.1016/j.molcel.2022.12.023Wang XH, Gao JW, Bao JP, Zhu L, Xie ZY, Chen L, et al. GATA4 promotes the senescence of nucleus pulposus cells via NF-KB pathway. Arch Gerontol Geriatr. 2022; 101: 104676. doi: 10.1016/j.archger.2022.104676Wang XH, Gao JW, Bao JP, Zhu L, Xie ZY, Chen L, et al. GATA4 promotes the senescence of nucleus pulposus cells via NF-KB pathway. Arch Gerontol Geriatr. 2022; 101: 104676. doi: 10.1016/j.archger.2022.104676Gong H, Chen H, Xiao P, Huang N, Han X, Zhang J, et al. miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation. Signal Transduct Target Ther. 2022; 7(1): 66. doi: 10.1038/s41392-022-00886-3Gong H, Chen H, Xiao P, Huang N, Han X, Zhang J, et al. miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation. Signal Transduct Target Ther. 2022; 7(1): 66. doi: 10.1038/s41392-022-00886-3Sławińska N, Krupa R. Molecular Aspects of Senescence and Organismal Ageing-DNA Damage Response, Telomeres, Inflammation and Chromatin. Int J Mol Sci. 2021; 22(2): 590. doi: 10.3390/ijms22020590Sławińska N, Krupa R. Molecular Aspects of Senescence and Organismal Ageing-DNA Damage Response, Telomeres, Inflammation and Chromatin. Int J Mol Sci. 2021; 22(2): 590. doi: 10.3390/ijms22020590Miller TE, El Farran CA, Couturier CP, Chen Z, D'Antonio JP, Verga J, et al. Programs, origins and immunomodulatory functions of myeloid cells in glioma. Nature. 2025; 640(8060): 1072-1082. doi: 10.1038/s41586-025-08633-8Miller TE, El Farran CA, Couturier CP, Chen Z, D'Antonio JP, Verga J, et al. Programs, origins and immunomodulatory functions of myeloid cells in glioma. Nature. 2025; 640(8060): 1072-1082. doi: 10.1038/s41586-025-08633-8Wang M, Wang H, Wang X, Shen Y, Zhou D, Jiang Y. Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration. Front Immunol. 2024; 15: 1439976. doi: 10.3389/fimmu.2024.1439976Wang M, Wang H, Wang X, Shen Y, Zhou D, Jiang Y. Identification of cellular senescence-related genes and immune cell infiltration characteristics in intervertebral disc degeneration. Front Immunol. 2024; 15: 1439976. doi: 10.3389/fimmu.2024.1439976Pańczyszyn A, Boniewska-Bernacka E, Goc A. The role of telomeres and telomerase in the senescence of postmitotic cells. DNA Repair (Amst). 2020; 95: 102956. doi: 10.1016/j.dnarep.2020.102956Pańczyszyn A, Boniewska-Bernacka E, Goc A. The role of telomeres and telomerase in the senescence of postmitotic cells. DNA Repair (Amst). 2020; 95: 102956. doi: 10.1016/j.dnarep.2020.102956Margiotti K, Monaco F, Fabiani M, Mesoraca A, Giorlandino C. Epigenetic Clocks: In Aging-Related and Complex Diseases. Cytogenet Genome Res. 2023; 163(5-6): 247-256. doi: 10.1159/000534561Margiotti K, Monaco F, Fabiani M, Mesoraca A, Giorlandino C. Epigenetic Clocks: In Aging-Related and Complex Diseases. Cytogenet Genome Res. 2023; 163(5-6): 247-256. doi: 10.1159/000534561Raj K, Horvath S. Current perspectives on the cellular and molecular features of epigenetic ageing. Exp Biol Med (Maywood). 2020; 245(17): 1532-1542. doi: 10.1177/1535370220918329Raj K, Horvath S. Current perspectives on the cellular and molecular features of epigenetic ageing. Exp Biol Med (Maywood). 2020; 245(17): 1532-1542. doi: 10.1177/1535370220918329Olan I, Handa T, Narita M. Beyond SAHF: An integrative view of chromatin compartmentalization during senescence. Curr Opin Cell Biol. 2023; 83: 102206. doi: 10.1016/j.ceb.2023.102206Olan I, Handa T, Narita M. Beyond SAHF: An integrative view of chromatin compartmentalization during senescence. Curr Opin Cell Biol. 2023; 83: 102206. doi: 10.1016/j.ceb.2023.102206Nicetto D, Zaret KS. Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev. 2019; 55: 1-10. doi: 10.1016/j.gde.2019.04.013.Nicetto D, Zaret KS. Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev. 2019; 55: 1-10. doi: 10.1016/j.gde.2019.04.013.Olan I, Handa T, Narita M. Beyond SAHF: An integrative view of chromatin compartmentalization during senescence. Curr Opin Cell Biol. 2023; 83: 102206. doi: 10.1016/j.ceb.2023.102206Olan I, Handa T, Narita M. Beyond SAHF: An integrative view of chromatin compartmentalization during senescence. Curr Opin Cell Biol. 2023; 83: 102206. doi: 10.1016/j.ceb.2023.102206Marcozzi S, Bigossi G, Giuliani ME, Giacconi R, Piacenza F, Cardelli M, et al. Cellular senescence and frailty: a comprehensive insight into the causal links. Geroscience. 2023; 45(6): 3267-3305. doi: 10.1007/s11357-023-00960-wMarcozzi S, Bigossi G, Giuliani ME, Giacconi R, Piacenza F, Cardelli M, et al. Cellular senescence and frailty: a comprehensive insight into the causal links. Geroscience. 2023; 45(6): 3267-3305. doi: 10.1007/s11357-023-00960-wChandra A, Lagnado AB, Farr JN, Doolittle M, Tchkonia T, Kirkland JL, et al. Targeted clearance of p21-but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity. Aging Cell. 2022; 21(5): e13602. doi: 10.1111/acel.13602Chandra A, Lagnado AB, Farr JN, Doolittle M, Tchkonia T, Kirkland JL, et al. Targeted clearance of p21-but not p16-positive senescent cells prevents radiation-induced osteoporosis and increased marrow adiposity. Aging Cell. 2022; 21(5): e13602. doi: 10.1111/acel.13602Cummings SR, Lui LY, Zaira A, Mau T, Fielding RA, Atkinson EJ, et al. Biomarkers of cellular senescence and major health outcomes in older adults. Geroscience. 2024. doi: 10.1007/s11357-024-01474-9. Epub ahead of print. Erratum in: Geroscience. 2025. doi: 10.1007/s11357-025-01619-4Cummings SR, Lui LY, Zaira A, Mau T, Fielding RA, Atkinson EJ, et al. Biomarkers of cellular senescence and major health outcomes in older adults. Geroscience. 2024. doi: 10.1007/s11357-024-01474-9. Epub ahead of print. Erratum in: Geroscience. 2025. doi: 10.1007/s11357-025-01619-4Fielding RA, Atkinson EJ, Aversa Z, White TA, Heeren AA, Achenbach SJ, et al. Associations between biomarkers of cellular senescence and physical function in humans: observations from the lifestyle interventions for elders (LIFE) study. Geroscience. 2022; 44(6): 2757-2770. doi: 10.1007/s11357-022-00685-2Fielding RA, Atkinson EJ, Aversa Z, White TA, Heeren AA, Achenbach SJ, et al. Associations between biomarkers of cellular senescence and physical function in humans: observations from the lifestyle interventions for elders (LIFE) study. Geroscience. 2022; 44(6): 2757-2770. doi: 10.1007/s11357-022-00685-2Madaeva IM, Kurashova NA, Titova EV, et al. Growth Differentiation Factor GDF 15 (“Protein of Senility”) under Conditions of Oxidative Stress and Intermittent Nocturnal Hypoxia in Patients with Sleep Apnea Syndrome. Adv Gerontol. 2024; 14: 61-67. doi: 10.1134/S2079057024600447Madaeva IM, Kurashova NA, Titova EV, et al. Growth Differentiation Factor GDF 15 (“Protein of Senility”) under Conditions of Oxidative Stress and Intermittent Nocturnal Hypoxia in Patients with Sleep Apnea Syndrome. Adv Gerontol. 2024; 14: 61-67. doi: 10.1134/S2079057024600447Артеменков А.А. Возраст-зависимая дисрегуляция иммунного ответа у человека. Медицинская иммунология. 2021; 23(5): 1005-1016. doi: 10.15789/1563-0625-ADO-2192Artemenkov AA. Age-dependent disregulation of the immune response in humans. Medical Immunology (Russia). 2021;23(5):1005-1016. (In Russ.). doi: 10.15789/1563-0625-ADO-2192Liu Y, Gu JJ, Yang L, Tsai PC, Guo Y, Xue K, et al. The adhesion molecule ICAM-1 in diffuse large B-cell lymphoma post-rituximab era: relationship with prognostic importance and rituximab resistance. Aging (Albany NY). 2020; 13(1): 181-193. doi: 10.18632/aging.202180Liu Y, Gu JJ, Yang L, Tsai PC, Guo Y, Xue K, et al. The adhesion molecule ICAM-1 in diffuse large B-cell lymphoma post-rituximab era: relationship with prognostic importance and rituximab resistance. Aging (Albany NY). 2020; 13(1): 181-193. doi: 10.18632/aging.202180Wang Q, Wang X, Liu B, Ma S, Zhang F, Sun S, et al. Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland. Nat Aging. 2024; 4(3): 396-413. doi: 10.1038/s43587-024-00588-1Wang Q, Wang X, Liu B, Ma S, Zhang F, Sun S, et al. Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland. Nat Aging. 2024; 4(3): 396-413. doi: 10.1038/s43587-024-00588-1Knezevic E, Nenic K, Milanovic V, Knezevic NN. The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells. 2023; 12(23): 2726. doi: 10.3390/cells12232726Knezevic E, Nenic K, Milanovic V, Knezevic NN. The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells. 2023; 12(23): 2726. doi: 10.3390/cells12232726Gao X, Li F, Liu B, Wang Y, Wang Y, Zhou H. Cellular Senescence in Adrenocortical Biology and Its Disorders. Cells. 2021; 10(12): 3474. doi: 10.3390/cells10123474Gao X, Li F, Liu B, Wang Y, Wang Y, Zhou H. Cellular Senescence in Adrenocortical Biology and Its Disorders. Cells. 2021; 10(12): 3474. doi: 10.3390/cells10123474Dowery R, Benhamou D, Benchetrit E, Harel O, Nevelsky A, Zisman-Rozen S, et al. Peripheral B cells repress B-cell regeneration in aging through a TNF-a/IGFBP-1/ IGF-1 immune-endocrine axis. Blood. 2021; 138(19): 1817-1829. doi: 10.1182/blood.2021012428Dowery R, Benhamou D, Benchetrit E, Harel O, Nevelsky A, Zisman-Rozen S, et al. Peripheral B cells repress B-cell regeneration in aging through a TNF-a/IGFBP-1/ IGF-1 immune-endocrine axis. Blood. 2021; 138(19): 1817-1829. doi: 10.1182/blood.2021012428Lee H, Lee SV. Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling in Caenorhabditis elegans. Mol Cells. 2022; 45(11): 763-770. doi: 10.14348/mol-cells.2022.0097Lee H, Lee SV. Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling in Caenorhabditis elegans. Mol Cells. 2022; 45(11): 763-770. doi: 10.14348/mol-cells.2022.0097Jauhari A, Baranov SV, Suofu Y, Kim J, Singh T, Yablonska S, et al. Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration. J Clin Invest. 2020; 130(6): 3124-3136. doi: 10.1172/JCI135026. Erratum in: J Clin Invest. 2021; 131(9): 150328. doi:10.1172/JCI150328Jauhari A, Baranov SV, Suofu Y, Kim J, Singh T, Yablonska S, et al. Melatonin inhibits cytosolic mitochondrial DNA-induced neuroinflammatory signaling in accelerated aging and neurodegeneration. J Clin Invest. 2020; 130(6): 3124-3136. doi: 10.1172/JCI135026. Erratum in: J Clin Invest. 2021; 131(9): 150328. doi:10.1172/JCI150328Lin LT, Li CJ, Lee YS, Tsui KH. Recombinant Follicle-Stimulating Hormone and Luteinizing Hormone Enhance Mitochondrial Function and Metabolism in Aging Female Reproductive Cells. Int J Mol Sci. 2024; 26(1): 83. doi: 10.3390/ijms26010083Lin LT, Li CJ, Lee YS, Tsui KH. Recombinant Follicle-Stimulating Hormone and Luteinizing Hormone Enhance Mitochondrial Function and Metabolism in Aging Female Reproductive Cells. Int J Mol Sci. 2024; 26(1): 83. doi: 10.3390/ijms26010083Wang Z, Yang T, Liu S, Chen Y. Effects of bone marrow mesenchymal stem cells on ovarian and testicular function in aging Sprague-Dawley rats induced by D-galactose. Cell Cycle. 2020; 19(18): 2340-2350. doi: 10.1080/15384101.2020.1806434Wang Z, Yang T, Liu S, Chen Y. Effects of bone marrow mesenchymal stem cells on ovarian and testicular function in aging Sprague-Dawley rats induced by D-galactose. Cell Cycle. 2020; 19(18): 2340-2350. doi: 10.1080/15384101.2020.1806434Lu W, Feng W, Lai J, Yuan D, Xiao W, Li Y. Role of adipokines in sarcopenia. Chin Med J (Engl). 2023; 136(15): 1794-1804. doi: 10.1097/CM9.0000000000002255Lu W, Feng W, Lai J, Yuan D, Xiao W, Li Y. Role of adipokines in sarcopenia. Chin Med J (Engl). 2023; 136(15): 1794-1804. doi: 10.1097/CM9.0000000000002255Kawakami F, Imai M, Isaka Y, Cookson MR, Maruyama H, Kubo M, et al. LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes. FEBS Open Bio. 2023; 13(12): 2200-2214. doi: 10.1002/2211-5463.13717Kawakami F, Imai M, Isaka Y, Cookson MR, Maruyama H, Kubo M, et al. LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes. FEBS Open Bio. 2023; 13(12): 2200-2214. doi: 10.1002/2211-5463.13717Kotolloshi R, Mirzakhani K, Ahlburg J, Kraft F, Pungsrinont T, Baniahmad A. Thyroid hormone induces cellular senescence in prostate cancer cells through induction of DEC1. J Steroid Biochem Mol Biol. 2020; 201: 105689. doi: 10.1016/j.jsbmb.2020.105689Kotolloshi R, Mirzakhani K, Ahlburg J, Kraft F, Pungsrinont T, Baniahmad A. Thyroid hormone induces cellular senescence in prostate cancer cells through induction of DEC1. J Steroid Biochem Mol Biol. 2020; 201: 105689. doi: 10.1016/j.jsbmb.2020.105689Rutledge J, Lehallier B, Zarifkar P, Losada PM, Shahid-Besanti M, Western D, et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease. Acta Neuropathol. 2024; 147(1): 52. doi: 10.1007/s00401-024-02706-0Rutledge J, Lehallier B, Zarifkar P, Losada PM, Shahid-Besanti M, Western D, et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease. Acta Neuropathol. 2024; 147(1): 52. doi: 10.1007/s00401-024-02706-0Valieva Y, Ivanova E, Fayzullin A, Kurkov A, Igrunkova A. Senescence-Associated в-Galactosidase Detection in Pathology. Diagnostics (Basel). 2022; 12(10): 2309. doi: 10.3390/diagnostics12102309Valieva Y, Ivanova E, Fayzullin A, Kurkov A, Igrunkova A. Senescence-Associated в-Galactosidase Detection in Pathology. Diagnostics (Basel). 2022; 12(10): 2309. doi: 10.3390/diagnostics12102309Marzullo M, El Mai M, Ferreira MG. Whole-mount Senescence-Associated Beta-Galactosidase (SA-e-GAL) Activity Detection Protocol for Adult Zebrafish. Bio Protoc. 2022; 12(13): e4457. doi: 10.21769/BioProtoc.4457Marzullo M, El Mai M, Ferreira MG. Whole-mount Senescence-Associated Beta-Galactosidase (SA-e-GAL) Activity Detection Protocol for Adult Zebrafish. Bio Protoc. 2022; 12(13): e4457. doi: 10.21769/BioProtoc.4457Cai Y, Zhou H, Zhu Y, Sun Q, Ji Y, Xue A, et al. Elimination of senescent cells by в-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Res. 2020; 30(7): 574-589. doi: 10.1038/s41422-020-0314-9Cai Y, Zhou H, Zhu Y, Sun Q, Ji Y, Xue A, et al. Elimination of senescent cells by в-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Res. 2020; 30(7): 574-589. doi: 10.1038/s41422-020-0314-9Mahmud S, Pitcher LE, Torbenson E, Robbins PD, Zhang L, Dong X. Developing transcriptomic signatures as a biomarker of cellular senescence. Ageing Res Rev. 2024; 99: 102403. doi: 10.1016/j.arr.2024.102403Mahmud S, Pitcher LE, Torbenson E, Robbins PD, Zhang L, Dong X. Developing transcriptomic signatures as a biomarker of cellular senescence. Ageing Res Rev. 2024; 99: 102403. doi: 10.1016/j.arr.2024.102403Yu S, Chen M, Xu L, Mao E, Sun S. A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence. Front Immunol. 2023; 14: 1175490. doi: 10.3389/fimmu.2023.1175490Yu S, Chen M, Xu L, Mao E, Sun S. A senescence-based prognostic gene signature for colorectal cancer and identification of the role of SPP1-positive macrophages in tumor senescence. Front Immunol. 2023; 14: 1175490. doi: 10.3389/fimmu.2023.1175490Evangelou K, Gorgoulis VG. Sudan Black B. The Specific Histochemical Stain for Lipofuscin: A Novel Method to Detect Senescent Cells. Methods Mol Biol. 2017; 1534: 111-119. doi: 10.1007/978-1-4939-6670-7_10Evangelou K, Gorgoulis VG. Sudan Black B. The Specific Histochemical Stain for Lipofuscin: A Novel Method to Detect Senescent Cells. Methods Mol Biol. 2017; 1534: 111-119. doi: 10.1007/978-1-4939-6670-7_10Vizioli MG, Liu T, Miller KN, Robertson NA, Gilroy K, Lagnado AB, et al. Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence. Genes Dev. 2020; 34(5-6): 428-445. doi: 10.1101/gad.331272.119Vizioli MG, Liu T, Miller KN, Robertson NA, Gilroy K, Lagnado AB, et al. Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence. Genes Dev. 2020; 34(5-6): 428-445. doi: 10.1101/gad.331272.119Lagnado A, Leslie J, Ruchaud-Sparagano MH, Victorelli S, Hirsova P, Ogrodnik M, et al. Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. EMBO J. 2021; 40(9): e106048. doi: 10.15252/embj.2020106048Lagnado A, Leslie J, Ruchaud-Sparagano MH, Victorelli S, Hirsova P, Ogrodnik M, et al. Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. EMBO J. 2021; 40(9): e106048. doi: 10.15252/embj.2020106048Salameh Y, Bejaoui Y, El Hajj N. DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet. 2020; 11: 171. doi: 10.3389/fgene.2020.00171Salameh Y, Bejaoui Y, El Hajj N. DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet. 2020; 11: 171. doi: 10.3389/fgene.2020.00171Kuehnemann C, Wiley CD. Senescent cells at the crossroads of aging, disease, and tissue homeostasis. Aging Cell. 2024; 23(1): e13988. doi: 10.1111/acel.13988Kuehnemann C, Wiley CD. Senescent cells at the crossroads of aging, disease, and tissue homeostasis. Aging Cell. 2024; 23(1): e13988. doi: 10.1111/acel.13988Iqbal W, Zhou W. Computational Methods for Single-cell DNA Methylome Analysis. Genomics Proteomics Bioinformatics. 2023; 21(1): 48-66. doi: 10.1016/j.gpb.2022.05.007Iqbal W, Zhou W. Computational Methods for Single-cell DNA Methylome Analysis. Genomics Proteomics Bioinformatics. 2023; 21(1): 48-66. doi: 10.1016/j.gpb.2022.05.007Mehdizadeh M, Aguilar M, Thorin E, Ferbeyre G, Nattel S. The role of cellular senescence in cardiac disease: basic biology and clinical relevance. Nat Rev Cardiol. 2022; 19(4): 250-264. doi: 10.1038/s41569-021-00624-2Mehdizadeh M, Aguilar M, Thorin E, Ferbeyre G, Nattel S. The role of cellular senescence in cardiac disease: basic biology and clinical relevance. Nat Rev Cardiol. 2022; 19(4): 250-264. doi: 10.1038/s41569-021-00624-2Khosla S, Farr JN, Tchkonia T, Kirkland JL. The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020; 16(5): 263-275. doi: 10.1038/s41574-020-0335-yKhosla S, Farr JN, Tchkonia T, Kirkland JL. The role of cellular senescence in ageing and endocrine disease. Nat Rev Endocrinol. 2020; 16(5): 263-275. doi: 10.1038/s41574-020-0335-yMcHugh D, Duran I, Gil J. Senescence as a therapeutic target in cancer and age-related diseases. Nat Rev Drug Discov. 2025; 24(1): 57-71. doi: 10.1038/s41573-024-01074-4McHugh D, Duran I, Gil J. Senescence as a therapeutic target in cancer and age-related diseases. Nat Rev Drug Discov. 2025; 24(1): 57-71. doi: 10.1038/s41573-024-01074-4Chambers CR, Ritchie S, Pereira BA, Timpson P. Overcoming the senescence-associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer. Mol Oncol. 2021; 15(12): 3242-3255. doi: 10.1002/1878-0261.13042Chambers CR, Ritchie S, Pereira BA, Timpson P. Overcoming the senescence-associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer. Mol Oncol. 2021; 15(12): 3242-3255. doi: 10.1002/1878-0261.13042

The authors declare that there are no conflicts of interest present.