DOI: https://dx.doi.org/10.18565/therapy.2024.10.125-133
В.А. Приходько, С.В. Оковитый
1) ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России; 2) ФГБОУ ВО «Санкт-Петербургский государственный университет»
1. Franceschi C., Bonafe M., Valensin S. et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000; 908: 244–54. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x. PMID: 10911963. 2. Mancuso P., Bouchard B. The impact of aging on adipose function and adipokine synthesis. Front Endocrinol (Lausanne). 2019; 10: 137. https://doi.org/10.3389/fendo.2019.00137. PMID: 30915034. PMCID: PMC6421296. 3. Guarner V., Rubio-Ruiz M.E. Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol. 2015; 40: 99–106. https://doi.org/10.1159/000364934. PMID: 25341516. 4. Курган Н.Д., Панова Е.И., Силакова Л.В. с соавт. Перспективы оценки биологического и иммунологического возраста человека по факторам крови. Наука и инновации в медицине. 2021; 6(4): 19–39. (Kurgan N.D., Panova E.I., Silakova L.V. et al. Prospects for assessing the biological and immunological age of a person by blood factors. Nauka i innovatsii v meditsine = Science & Innovations in Medicine. 2021; 6(4): 19–39 (In Russ.)). https://doi.org/10.35693/2500-1388-2021-6-4-19-39. EDN: EYAERX. 5. Prata L.G.P.L., Ovsyannikova I.G., Tchkonia T., Kirkland J.L. Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Semin Immunol. 2018; 40: 101275. https://doi.org/10.1016/j.smim.2019.04.003. PMID: 31088710. PMCID: PMC7061456. 6. Hoenicke L., Zender L. Immune surveillance of senescent cells – biological significance in cancer- and non-cancer pathologies. Carcinogenesis. 2012; 33(6): 1123–26. https://doi.org/10.1093/carcin/bgs124. PMID: 22470164. 7. Ovadya Y., Landsberger T., Leins H. et al. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun. 2018; 9(1): 5435. https://doi.org/10.1038/s41467-018-07825-3. PMID: 30575733. PMCID: PMC6303397. 8. Lin Y., Li Q., Liang G. et al. Overview of innate immune cell landscape in liver aging. Int J Mol Sci. 2023; 25(1): 181. https://doi.org/10.3390/ijms25010181. PMID: 38203352. PMCID: PMC10778796. 9. Grizzi F., Di Caro G., Laghi L. et al. Mast cells and the liver aging process. Immun Ageing. 2013; 10(1): 9. https://doi.org/10.1186/1742-4933-10-9. PMID: 23496863. PMCID: PMC3599827. 10. Hunt N.J., Kang S.W.S., Lockwood G.P. et al. Hallmarks of aging in the liver. Comput Struct Biotechnol J. 2019; 17: 1151–61. https://doi.org/10.1016/j.csbj.2019.07.021. PMID: 31462971. PMCID: PMC6709368. 11. Bangru S., Kalsotra A. Cellular and molecular basis of liver regeneration. Semin Cell Dev Biol. 2020; 100: 74–87. https://doi.org/10.1016/j.semcdb.2019.12.004. PMID: 31980376. PMCID: PMC7108750. 12. Palmisano B.T., Zhu L., Stafford J.M. Role of estrogens in the regulation of liver lipid metabolism. Adv Exp Med Biol. 2017; 1043: 227–56. https://doi.org/10.1007/978-3-319-70178-3_12. PMID: 29224098. PMCID: PMC5763482. 13. Nucci R.A.B., Teodoro A.C.S., Neto W.K. et al. Effects of testosterone administration on liver structure and function in aging rats. Aging Male. 2017; 20(2): 134–37. https://doi.org/10.1080/13685538.2017.1284779. PMID: 28590831. 14. Tsuneki H., Tokai E., Nakamura Y. et al. Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice. Diabetes. 2015; 64(2): 459–70. https://doi.org/10.2337/db14-0695. PMID: 25249578. 15. Terziev D., Terzieva D. Experimental data on the role of melatonin in the pathogenesis of nonalcoholic fatty liver disease. Biomedicines. 2023; 11(6): 1722. https://doi.org/10.3390/biomedicines11061722. PMID: 37371817. PMCID: PMC10296645. 16. Giunta S., Xia S., Pelliccioni G., Olivieri F. Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies. Geroscience. 2024; 46(1): 113–27. https://doi.org/10.1007/s11357-023-00947-7. PMID: 37821752. PMCID: PMC10828245. 17. Amir M., Yu M., He P., Srinivasan S. Hepatic autonomic nervous system and neurotrophic factors regulate the pathogenesis and progression of non-alcoholic fatty liver disease. Front Med (Lausanne). 2020; 7: 62. https://doi.org/10.3389/fmed.2020.00062. PMID: 32175323. PMCID: PMC7056867. 18. Poulose N., Raju R. Aging and injury: Alterations in cellular energetics and organ function. Aging Dis. 2014; 5(2): 101–8. https://doi.org/10.14336/AD.2014.0500101. PMID: 24729935. PMCID: PMC3966668. 19. Кайбышева В.О., Жарова М.Е., Филимендикова К.Ю., Никонов Е.Л. Микробиом человека: возрастные изменения и функции. Доказательная гастроэнтерология. 2020; 9(2): 42–55. (Kaybysheva V.O., Zharova M.E., Filimendikova K.Yu., Nikonov E.L. Human microbiome: age-related changes and functions. Dokazatel’naya gastroenterologiya = Russian Journal of Evidence-Based Gastroenterology. 2020; 9(2): 42–55 (In Russ.)). https://doi.org/10.17116/dokgastro2020902142. EDN: YKXBBQ. 20. Fusco W., Lorenzo M.B., Cintoni M. et al. Short-chain fatty-acid-producing bacteria: Key components of the human gut microbiota. Nutrients. 2023; 15(9): 2211. https://doi.org/10.3390/nu15092211. PMID: 37432351. PMCID: PMC10180739. 21. Zeng S.-Y., Liu Y.-F., Liu J.-H. et al. Potential effects of Akkermansia muciniphila in aging and aging-related diseases: Current evidence and perspectives. Aging Dis. 2023; 14(6): 2015–27. https://doi.org/10.14336/AD.2023.0325. PMID: 37199577. PMCID: PMC10676789. 22. Visekruna A., Luu M. The role of short-chain fatty acids and bile acids in intestinal and liver function, inflammation, and carcinogenesis. Front Cell Dev Biol. 2021; 9: 703218. https://doi.org/10.3389/fcell.2021.703218. PMID: 34381785. PMCID: PMC8352571. 23. Frommherz L., Bub A., Hummel E. et al. Age-related changes of plasma bile acid concentrations in healthy adults – results from the cross-sectional KarMeN Study. PLoS One. 2016; 11(4): e0153959. https://doi.org/10.1371/journal.pone.0153959. PMID: 27092559. PMCID: PMC4836658. 24. Chen Z., Ruan J., Li D. et al. The role of intestinal bacteria and gut-brain axis in hepatic encephalopathy. Front Cell Infect Microbiol. 2021; 10: 595759. https://doi.org/10.3389/fcimb.2020.595759. PMID: 33553004. PMCID: PMC7859631. 25. Wiemann S.U., Satyanarayana A., Tsahuridu M. et al. Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. FASEB J. 2002; 16(9): 935–42. https://doi.org/10.1096/fj.01-0977com. PMID: 12087054. 26. Chipchase M.D., O’Neill M., Melton D.W. Characterization of premature liver polyploidy in DNA repair (Ercc1)-deficient mice. Hepatology. 2003; 38(4): 958–66. https://doi.org/10.1053/jhep.2003.50421. PMID: 14512883. 27. Лазебник Л.Б., Ильченко Л.Ю. Возрастные изменения печени (клинические и морфологические аспекты). Клиническая геронтология. 2007; 13(1): 3–8. (Lazebnik L.B., Ilchenko L.Yu. Age liver changes (clinical and morphological aspects). Klinicheskaya gerontologiya = Clinical Gerontology. 2007; 13(1): 3–8 (In Russ.)). EDN: JHCYRP. 28. Irvine K.M., Skoien R., Bokil N.J. et al. Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration. World J Gastroenterol. 2014; 20(47): 17851–62. https://doi.org/10.3748/wjg.v20.i47.17851. PMID: 25548483. PMCID: PMC4273135. 29. Huda N., Liu G., Hong H. et al. Hepatic senescence, the good and the bad. World J Gastroenterol. 2019; 25(34): 5069–81. https://doi.org/10.3748/wjg.v25.i34.5069. PMID: 31558857. PMCID: PMC6747293. 30. Matsutani T., Kang S.C., Miyashita M. et al. Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice. Am J Physiol Gastrointest Liver Physiol. 2007; 292(1): G268–74. https://doi.org/10.1152/ajpgi.00313.2006. PMID: 16959950. 31. Aravinthan A., Challis B., Shannon N. et al. Selective insulin resistance in hepatocyte senescence. Exp Cell Res. 2015; 331(1): 38–45. https://doi.org/10.1016/j.yexcr.2014.09.025. PMID: 25263463. 32. Bonnet L., Alexandersson I., Baboota R.K. et al. Cellular senescence in hepatocytes contributes to metabolic disturbances in NASH. Front Endocrinol (Lausanne). 2022; 13: 957616. https://doi.org/10.3389/fendo.2022.957616. PMID: 36072934. PMCID: PMC9441597. 33. Ghiraldini F.G., Silva I.S., Mello M.L.S. Polyploidy and chromatin remodeling in hepatocytes from insulin-dependent diabetic and normoglycemic aged mice. Cytometry A. 2012; 81(9): 755–64. https://doi.org/10.1002/cyto.a.22102. PMID: 22837107. 34. Navarro A., Boveris A. Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Regul Integr Comp Physiol. 2004; 287(5): R1244–49. https://doi.org/10.1152/ajpregu.00226.2004. PMID: 15271654. 35. Daum B., Walter A., Horst A. et al. Age-dependent dissociation of ATP synthase dimers and loss of inner-membrane cristae in mitochondria. Proc Natl Acad Sci U S A. 2013; 110(38): 15301–6. https://doi.org/10.1073/pnas.1305462110. PMID: 24006361. PMCID: PMC3780843. 36. Aravinthan A.D., Alexander G.J. Hepatocyte senescence explains conjugated bilirubinaemia in chronic liver failure. J Hepatol. 2015; 63(2): 532–33. https://doi.org/10.1016/j.jhep.2015.03.031. PMID: 25839405. 37. Tabibian J.H., O’Hara S.P., Splinter P.L. et al. Cholangiocyte senescence by way of N-ras activation is a characteristic of primary sclerosing cholangitis. Hepatology. 2014; 59(6): 2263–75. https://doi.org/10.1002/hep.26993. PMID: 24390753. PMCID: PMC4167827. 38. Ferreira-Gonzalez S., Lu W.-Y., Raven A. et al. Paracrine cellular senescence exacerbates biliary injury and impairs regeneration. Nat Commun. 2018; 9(1): 1020. https://doi.org/10.1038/s41467-018-03299-5. PMID: 29523787. PMCID: PMC5844882. 39. Cazzagon N., Sarcognato S., Floreani A. et al. Cholangiocyte senescence in primary sclerosing cholangitis is associated with disease severity and prognosis. JHEP Rep. 2021; 3(3): 100286. https://doi.org/10.1016/j.jhepr.2021.100286. PMID: 34041468. PMCID: PMC8141934. 40. Meadows V., Baiocchi L., Kundu D. et al. Biliary epithelial senescence in liver disease: There will be SASP. Front Mol Biosci. 2021; 8: 803098. https://doi.org/10.3389/fmolb.2021.803098. PMID: 34993234. PMCID: PMC8724525. 41. Al Suraih M.S., Trussoni C.E., Splinter P.L. et al. Senescent cholangiocytes release extracellular vesicles that alter target cell phenotype via the epidermal growth factor receptor. Liver Int. 2020; 40(10): 2455–68. https://doi.org/10.1111/liv.14569. PMID: 32558183. PMCID: PMC7669612. 42. Maeso-Díaz R., Ortega-Ribera M., Fernández-Iglesias A. et al. Effects of aging on liver microcirculatory function and sinusoidal phenotype. Aging Cell. 2018; 17(6): e12829. https://doi.org/10.1111/acel.12829. PMID: 30260562. PMCID: PMC6260924. 43. Grosse L., Bulavin D.V. LSEC model of aging. Aging (Albany NY). 2020; 12(11): 11152–60. https://doi.org/10.18632/aging.103492. PMID: 32535553. PMCID: PMC7346042. 44. Le Couteur D.G., Cogger V.C., McCuskey R.S. et al. Age-related changes in the liver sinusoidal endothelium: A mechanism for dyslipidemia. Ann N Y Acad Sci. 2007; 1114: 79–87. https://doi.org/10.1196/annals.1396.003. PMID: 17804522. 45. Cogger V.C., Svistounov D., Warren A. et al. Liver aging and pseudocapillarization in a Werner syndrome mouse model. J Gerontol A Biol Sci Med Sci. 2014; 69(9): 1076–86. https://doi.org/10.1093/gerona/glt169. PMID: 24149428. PMCID: PMC4158411. 46. Duan J.-L., Liu J.-J., Ruan B. et al. Age-related liver endothelial zonation triggers steatohepatitis by inactivating pericentral endothelium-derived C-kit. Nat Aging. 2023; 3(3): 258–74. https://doi.org/10.1038/s43587-022-00348-z. PMID: 37118422. 47. van der Loo B., Labugger R., Aebischer C.P. et al. Age-related changes of vitamin A status. J Cardiovasc Pharmacol. 2004; 43(1): 26–30. https://doi.org/10.1097/00005344-200401000-00005. PMID: 14668564. 48. Krizhanovsky V., Yon M., Dickins R.A. et al. Senescence of activated stellate cells limits liver fibrosis. Cell. 2008; 134(4): 657–67. https://doi.org/10.1016/j.cell.2008.06.049. PMID: 18724938. PMCID: PMC3073300. 49. Verma S., Tachtatzis P., Penrhyn-Lowe S. et al. Sustained telomere length in hepatocytes and cholangiocytes with increasing age in normal liver. Hepatology. 2012; 56(4): 1510–20. https://doi.org/10.1002/hep.25787. PMID: 22504828. 50. Cheng N., Kim K.-H., Lau L.F. Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2. JCI Insight. 2022; 7(14): e158207. https://doi.org/10.1172/jci.insight.158207. PMID: 35708907. PMCID: PMC9431681. 51. Bloomer S.A., Moyer E.D. Hepatic macrophage accumulation with aging: Cause for concern? Am J Physiol Gastrointest Liver Physiol. 2021; 320(4): G496–G505. https://doi.org/10.1152/ajpgi.00286.2020. PMID: 33470190. 52. Heil M.F., Dingman A.D., Garvey J.S. Antigen handling in ageing. III. Age-related changes in antigen handling by liver parenchymal and nonparenchymal cells. Mech Ageing Dev. 1984; 26(2–3): 327–40. https://doi.org/10.1016/0047-6374(84)90104-0. PMID: 6482526. 53. Stahl E.C., Haschak M.J., Popovic B., Brown B.N. Macrophages in the aging liver and age-related liver disease. Front Immunol. 2018; 9: 2795. https://doi.org/10.3389/fimmu.2018.02795. PMID: 30555477. PMCID: PMC6284020. 54. Hilmer S.N., Cogger V.C., Le Couteur D.G. Basal activity of Kupffer cells increases with old age. J Gerontol A Biol Sci Med Sci. 2007; 62(9): 973–78. https://doi.org/10.1093/gerona/62.9.973. PMID: 17895435. 55. Sun W.B., Li K., Ma R.L., Han B.L. Effect of aging on Kupffer cell membrane phospholipid function: Modulation by vitamin E. World J Gastroenterol. 1996; 2(4): 215–17. https://doi.org/10.3748/wjg.v2.i4.215. 56. Li L., Cui L., Lin P. et al. Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers. Cell Stem Cell. 2023; 30(3): 283–299.e9. https://doi.org/10.1016/j.stem.2023.01.009. PMID: 36787740. 57. Aging Biomarker Consortium, Jiang M., Zheng Z., Wang X. et al. A biomarker framework for liver aging: The Aging Biomarker Consortium consensus statement. Life Medicine. 2024; 3(1): lnae004. https://doi.org/10.1093/lifemedi/lnae004.
Вероника Александровна Приходько, к. биол. н., старший преподаватель кафедры фармакологии и клинической фармакологии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России. Адрес: 197022, г. Санкт-Петербург, ул. Профессора Попова, д. 14, лит. А.
E-mail: veronika.prihodko@pharminnotech.com
ORCID: https://orcid.org/0000-0002-4690-1811
Сергей Владимирович Оковитый, д. м. н., профессор, заведующий кафедрой фармакологии и клинической фармакологии ФГБОУ ВО «Санкт-Петербургский государственный химико-фармацевтический университет» Минздрава России, профессор Научно-клинического и образовательного центра гастроэнтерологии и гепатологии ФГБОУ ВО «Санкт-Петербургский государственный университет». Адрес: 197022, г. Санкт-Петербург,
ул. Профессора Попова, д. 14, лит. А.
E-mail: sergey.okovity@pharminnotech.com
ORCID: https://orcid.org/0000-0003-4294-5531