免疫老化阻止による抗加齢対策 加齢性難聴の予防
加齢の進行に免疫老化が深く関与していることが明らかになってきた。また，蝸牛老化にも同様の機序が存在することが報告されるようになった。そこには，慢性炎症（chronic inflammation）と加齢（aging）とを合わせたInflamm-Aging（加齢性慢性炎症）という言葉や，さらに，酸化ストレス（oxidative stress）を加えたOxi-Inflamm-Aging（加齢性酸化慢性炎症）という新しい考え方が示されてきた。本稿では，第4回日本耳鼻咽喉科免疫アレルギー感染症学会学術講演会（2024年，大阪）にて筆者が行った会長講演の内容に沿い，免疫学的視点からの抗加齢に向けた基礎研究...
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| Published in | 日本耳鼻咽喉科免疫アレルギー感染症学会誌 Vol. 4; no. 3; pp. 113 - 121 |
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| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本耳鼻咽喉科免疫アレルギー感染症学会
2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2435-7952 |
| DOI | 10.24805/jiaio.4.3_113 |
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| Abstract | 加齢の進行に免疫老化が深く関与していることが明らかになってきた。また，蝸牛老化にも同様の機序が存在することが報告されるようになった。そこには，慢性炎症（chronic inflammation）と加齢（aging）とを合わせたInflamm-Aging（加齢性慢性炎症）という言葉や，さらに，酸化ストレス（oxidative stress）を加えたOxi-Inflamm-Aging（加齢性酸化慢性炎症）という新しい考え方が示されてきた。本稿では，第4回日本耳鼻咽喉科免疫アレルギー感染症学会学術講演会（2024年，大阪）にて筆者が行った会長講演の内容に沿い，免疫学的視点からの抗加齢に向けた基礎研究，特に免疫若返りによる加齢性難聴予防について紹介するとともに，臨床応用について考察する。 |
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| AbstractList | 加齢の進行に免疫老化が深く関与していることが明らかになってきた。また，蝸牛老化にも同様の機序が存在することが報告されるようになった。そこには，慢性炎症（chronic inflammation）と加齢（aging）とを合わせたInflamm-Aging（加齢性慢性炎症）という言葉や，さらに，酸化ストレス（oxidative stress）を加えたOxi-Inflamm-Aging（加齢性酸化慢性炎症）という新しい考え方が示されてきた。本稿では，第4回日本耳鼻咽喉科免疫アレルギー感染症学会学術講演会（2024年，大阪）にて筆者が行った会長講演の内容に沿い，免疫学的視点からの抗加齢に向けた基礎研究，特に免疫若返りによる加齢性難聴予防について紹介するとともに，臨床応用について考察する。 |
| Author | 岩井, 大 |
| Author_xml | – sequence: 1 fullname: 岩井, 大 organization: 関西医科大学耳鼻咽喉科・頭頸部外科学講座 |
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| Copyright | 2024 日本耳鼻咽喉科免疫アレルギー感染症学会 |
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| References | 13)Iwai H, Lee S, Inaba M, et al.: Correlation between accelerated presbycusis and decreased immune functions. Exp Gerontol 2003; 38: 319–325. doi: 10.1016/s0531-5565(02)00177-8. 35)Mannick JB, Del Giudice GD, Lattanzi M, et al.: mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014; 6: 268ra179. doi: 10.1126/scitranslmed.3009892. 1)Gates GA, Mills JH: Presbycusis. Lancet 2005; 366: 1111–1120. doi: 10.1016/S0140-6736(05)67423-5. 31)Capaccio P, Pignataro L, Gaini LM, et al.: Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol 2012; 269, 449–453. doi: 10.1007/s00405-011-1671-2. 7)Someya S, Tanokura M, Weindruch R, et al.: Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 2010; 3: 20–25. doi: 10.2174/1874609811003010020. 38)Yousefzadeh MJ, Flores RR, Zhu Y, et al.: An aged immune system drives senescence and ageing of solid organs, Nature 2021; 594: 100–105. doi: 10.1038/s41586-021-03547-7. 24)Iwai H, Baba S, Omae M, et al.: Maintenance of systemic immune functions prevents accelerated presbycusis. Brain Res 2008; 1208: 8–16. doi: 10.1016/j.brainres.2008.02.069. 21)Iwai H, Inaba M, Van DB, et al.: Prevention of hearing loss by alteration of the systemic immune system. Adv Aging Res 2019; 8: 29–41. doi: 10.4236/aar.2019.82003 37)Fang B, Xiao H: Rapamycin alleviates cisplatin-induced ototoxicity in vivo. Biochem Biophys Res Commun 2014; 448, 443–447. doi: 10.1016/j.bbrc.2014.04.123. 8)Han C, Ding D, Lopez MC, et al.: Effects of long-term exercise on age-related hearing loss in mice. J Neurosci 2016; 36: 11308–11319. doi: 10.1523/JNEUROSCI.2493-16.2016. 5)Christensen K, Frederiksen H, Hoffman HJ: Genetic and environmental influences on self-reported reduced hearing in the old and oldest old. J Am Geriatr Soc 2001; 49: 1512–1517. 30)Hwang JH, Chen JC, Hsu CJ, et al.: Plasma reactive oxygen species levels are correlated with severity of age-related hearing impairment in humans. Neurobiol Aging 2012; 33: 1920–1926. doi: 10.1016/j.neurobiolaging.2011.10.012. 33)Akiyama T, Ishida J, Nakagawa S, et al.: Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987; 262: 5592–5595. doi: 10.1016/S0021-9258(18)45614-1. 10)Ligotti ME, Aiello A, Giulia Accardi G, et al.: Analysis of T and NK cell subsets in the Sicilian population from young to supercentenarian: The role of age and gender. Clin Exp Immunol 2021; 205: 198–212. doi: 10.1111/cei.13606. 15)de Toda IM, Ceprián N, Cerro EDD, et al.: The role of immune cells in oxi-inflamm-aging. Cells 2021; 10: 2974. doi: 10.3390/cells10112974. 32)Tan M, Toplu Y, Varan E, et al.: The effect of genistein on cisplatin induced ototoxicity and oxidative stress. Braz J Otorhinolaryngol 2022; 88: 105–111. doi: 10.1016/j.bjorl.2021.07.001. 34)Wei W, Ji S: Cellular senescence: molecular mechanisms and pathogenicity. J Cell Physiol 2018; 233: 9121–9135. doi: 10.1002/jcp.26956. 36)Guo S, Xu N, Chen P, et al.: Rapamycin protects spiral ganglion neurons from gentamicin-induced degeneration in vitro. J Assoc Res Otolaryngol 2019; 20: 475–487. doi: 10.1007/s10162-019-00717-3. 27)Iwai H, Inaba M, Bui DV, et al.: Treg and IL-1 receptor type 2-expressing CD4+ T cell-deleted CD4+ T cell fraction prevents the progression of age-related hearing loss in a mouse model. J Neuroimmunol 2021; 357: 577628. doi: 10.1016/j.jneuroim.2021.577628. 3)Warner HR, Butler RN, Sprott RL, et al.; Modern biological theories of aging. Raven Press, New York. 1987. 29)Watson N, Ding B, Zhu X, et al.: Chronic inflammation – inflammaging – in the ageing cochlea: A novel target for future presbycusis therapy. Ageing Res Rev 2017; 40, 142–148. doi: 10.1016/j.arr.2017.10.002. 6)Karlsson KK, Harris JR, Svartengren M: Description and primary results from an audiometric study of male twins. Ear Hear 1997; 18: 114–120. 20)Iwai H, Lee S, Inaba M, et al.: Bone marrow transplantation as a strategy for the treatment of autoimmune hearing loss in MRL/Mp-lpr/lpr mice. J Neuroimmunol 2005; 168: 76–82. doi: 10.1016/j.jneuroim.2005.07.020. 2)Lin FR, Thorpe R, Gordon-Salant S, et al.: Hearing loss prevalence and risk factors among older adults in the United States. J Gerontol A Biol Sci Med Sci 2011; 66: 582–590. doi: 10.1093/gerona/glr002. 22)Mitani A, Iwai H, Inaba M, et al.: Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model. Exp Gerontol 2023; 177: 112184. doi: 10.1016/j.exger.2023.112184. 11)Borgoni S, Kudryashova KS, Burka K, et al.: Targeting immune dysfunction in aging, Ageing Res Rev 2021; 70: 101410. doi: 10.1016/j.arr.2021.101410. 18)Ohtani N: The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis? Inflamm Regen 2022; 42: 11. doi: 10.1186/s41232-022-00197-8. 4)近藤祥司：細胞老化の過去，現在，未来．基礎老化研究 2020; 44: 13–18. 17)Haberthur K, Engelman F, Barron A, et al.: Immune senescence in aged nonhuman primates. Exp Gerontol 2010; 45: 655–661. doi: 10.1016/j.exger.2010.06.001. 28)Casciaro M, Di Salvo E, Pace E, et al.: Chlorinative stress in age-related diseases: a literature review. Immun Ageing 2017; 14: 21. doi: 10.1186/s12979-017-0104-5. 9)Coppe JP, Patil CK, Rodier F, et al.: Senescence associated secretory phenotypes reveal cell nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6: 2853–2868. 23)Iwai H, Lee S, Inaba M, et al.: Prevention of accelerated presbycusis by bone marrow transplantation in senescence accelerated mice. Bone Marrow Transplant 2001; 28: 323–328. doi: 10.1038/sj.bmt.1703152. 12)Hosono M, Hanada K, Toichi E, et al.: Immune abnormality inrelation to nonimmune diseases in SAM mice. Exp Gerontol 1997; 32: 181–195. DOI: 10.1016/s0531-5565(96)00070-8 19)Kovina MV, Karnaukhov AV, Krasheninnikov ME, et al.: Extension of maximal lifespan and high bone marrow chimerism after nonmyeloablative syngeneic transplantation of bone marrow from young to old mice. Front Genet 2019; 10: 310. doi: 10.3389/fgene.2019.00310. 16)Accardi G, Caruso C: Immune-inflammatory responses in the elderly: an update. Immun Ageing 2018; 15: 11. doi: 10.1186/s12979-018-0117-8. 25)Iwai H, Inaba M: Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-Positive T cells expressing IL-1 receptor type 2 and regulatory T Cells. Immun Ageing 2015; 12: 26. doi: 10.1186/s12979-015-0053-9. 14)Franceschi C, Campisi J: Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 2014; 69(Suppl 1): S4–S9. doi: 10.1093/gerona/glu057. 26)Iwai H, Yasumizu R, Sugiura K, et al.: Successful pancreas allografts in combination with bone marrow transplantation in mice. Immunology 1987; 62: 457–462. |
| References_xml | – reference: 10)Ligotti ME, Aiello A, Giulia Accardi G, et al.: Analysis of T and NK cell subsets in the Sicilian population from young to supercentenarian: The role of age and gender. Clin Exp Immunol 2021; 205: 198–212. doi: 10.1111/cei.13606. – reference: 33)Akiyama T, Ishida J, Nakagawa S, et al.: Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987; 262: 5592–5595. doi: 10.1016/S0021-9258(18)45614-1. – reference: 34)Wei W, Ji S: Cellular senescence: molecular mechanisms and pathogenicity. J Cell Physiol 2018; 233: 9121–9135. doi: 10.1002/jcp.26956. – reference: 12)Hosono M, Hanada K, Toichi E, et al.: Immune abnormality inrelation to nonimmune diseases in SAM mice. Exp Gerontol 1997; 32: 181–195. DOI: 10.1016/s0531-5565(96)00070-8 – reference: 32)Tan M, Toplu Y, Varan E, et al.: The effect of genistein on cisplatin induced ototoxicity and oxidative stress. Braz J Otorhinolaryngol 2022; 88: 105–111. doi: 10.1016/j.bjorl.2021.07.001. – reference: 36)Guo S, Xu N, Chen P, et al.: Rapamycin protects spiral ganglion neurons from gentamicin-induced degeneration in vitro. J Assoc Res Otolaryngol 2019; 20: 475–487. doi: 10.1007/s10162-019-00717-3. – reference: 4)近藤祥司：細胞老化の過去，現在，未来．基礎老化研究 2020; 44: 13–18. – reference: 35)Mannick JB, Del Giudice GD, Lattanzi M, et al.: mTOR inhibition improves immune function in the elderly. Sci Transl Med 2014; 6: 268ra179. doi: 10.1126/scitranslmed.3009892. – reference: 37)Fang B, Xiao H: Rapamycin alleviates cisplatin-induced ototoxicity in vivo. Biochem Biophys Res Commun 2014; 448, 443–447. doi: 10.1016/j.bbrc.2014.04.123. – reference: 7)Someya S, Tanokura M, Weindruch R, et al.: Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 2010; 3: 20–25. doi: 10.2174/1874609811003010020. – reference: 16)Accardi G, Caruso C: Immune-inflammatory responses in the elderly: an update. Immun Ageing 2018; 15: 11. doi: 10.1186/s12979-018-0117-8. – reference: 8)Han C, Ding D, Lopez MC, et al.: Effects of long-term exercise on age-related hearing loss in mice. J Neurosci 2016; 36: 11308–11319. doi: 10.1523/JNEUROSCI.2493-16.2016. – reference: 25)Iwai H, Inaba M: Fetal thymus graft enables recovery from age-related hearing loss and expansion of CD4-Positive T cells expressing IL-1 receptor type 2 and regulatory T Cells. Immun Ageing 2015; 12: 26. doi: 10.1186/s12979-015-0053-9. – reference: 3)Warner HR, Butler RN, Sprott RL, et al.; Modern biological theories of aging. Raven Press, New York. 1987. – reference: 22)Mitani A, Iwai H, Inaba M, et al.: Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model. Exp Gerontol 2023; 177: 112184. doi: 10.1016/j.exger.2023.112184. – reference: 9)Coppe JP, Patil CK, Rodier F, et al.: Senescence associated secretory phenotypes reveal cell nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6: 2853–2868. – reference: 6)Karlsson KK, Harris JR, Svartengren M: Description and primary results from an audiometric study of male twins. Ear Hear 1997; 18: 114–120. – reference: 26)Iwai H, Yasumizu R, Sugiura K, et al.: Successful pancreas allografts in combination with bone marrow transplantation in mice. Immunology 1987; 62: 457–462. – reference: 28)Casciaro M, Di Salvo E, Pace E, et al.: Chlorinative stress in age-related diseases: a literature review. Immun Ageing 2017; 14: 21. doi: 10.1186/s12979-017-0104-5. – reference: 20)Iwai H, Lee S, Inaba M, et al.: Bone marrow transplantation as a strategy for the treatment of autoimmune hearing loss in MRL/Mp-lpr/lpr mice. J Neuroimmunol 2005; 168: 76–82. doi: 10.1016/j.jneuroim.2005.07.020. – reference: 29)Watson N, Ding B, Zhu X, et al.: Chronic inflammation – inflammaging – in the ageing cochlea: A novel target for future presbycusis therapy. Ageing Res Rev 2017; 40, 142–148. doi: 10.1016/j.arr.2017.10.002. – reference: 14)Franceschi C, Campisi J: Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 2014; 69(Suppl 1): S4–S9. doi: 10.1093/gerona/glu057. – reference: 2)Lin FR, Thorpe R, Gordon-Salant S, et al.: Hearing loss prevalence and risk factors among older adults in the United States. J Gerontol A Biol Sci Med Sci 2011; 66: 582–590. doi: 10.1093/gerona/glr002. – reference: 5)Christensen K, Frederiksen H, Hoffman HJ: Genetic and environmental influences on self-reported reduced hearing in the old and oldest old. J Am Geriatr Soc 2001; 49: 1512–1517. – reference: 17)Haberthur K, Engelman F, Barron A, et al.: Immune senescence in aged nonhuman primates. Exp Gerontol 2010; 45: 655–661. doi: 10.1016/j.exger.2010.06.001. – reference: 31)Capaccio P, Pignataro L, Gaini LM, et al.: Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol 2012; 269, 449–453. doi: 10.1007/s00405-011-1671-2. – reference: 21)Iwai H, Inaba M, Van DB, et al.: Prevention of hearing loss by alteration of the systemic immune system. Adv Aging Res 2019; 8: 29–41. doi: 10.4236/aar.2019.82003 – reference: 24)Iwai H, Baba S, Omae M, et al.: Maintenance of systemic immune functions prevents accelerated presbycusis. Brain Res 2008; 1208: 8–16. doi: 10.1016/j.brainres.2008.02.069. – reference: 13)Iwai H, Lee S, Inaba M, et al.: Correlation between accelerated presbycusis and decreased immune functions. Exp Gerontol 2003; 38: 319–325. doi: 10.1016/s0531-5565(02)00177-8. – reference: 11)Borgoni S, Kudryashova KS, Burka K, et al.: Targeting immune dysfunction in aging, Ageing Res Rev 2021; 70: 101410. doi: 10.1016/j.arr.2021.101410. – reference: 38)Yousefzadeh MJ, Flores RR, Zhu Y, et al.: An aged immune system drives senescence and ageing of solid organs, Nature 2021; 594: 100–105. doi: 10.1038/s41586-021-03547-7. – reference: 23)Iwai H, Lee S, Inaba M, et al.: Prevention of accelerated presbycusis by bone marrow transplantation in senescence accelerated mice. Bone Marrow Transplant 2001; 28: 323–328. doi: 10.1038/sj.bmt.1703152. – reference: 15)de Toda IM, Ceprián N, Cerro EDD, et al.: The role of immune cells in oxi-inflamm-aging. Cells 2021; 10: 2974. doi: 10.3390/cells10112974. – reference: 18)Ohtani N: The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis? Inflamm Regen 2022; 42: 11. doi: 10.1186/s41232-022-00197-8. – reference: 19)Kovina MV, Karnaukhov AV, Krasheninnikov ME, et al.: Extension of maximal lifespan and high bone marrow chimerism after nonmyeloablative syngeneic transplantation of bone marrow from young to old mice. Front Genet 2019; 10: 310. doi: 10.3389/fgene.2019.00310. – reference: 27)Iwai H, Inaba M, Bui DV, et al.: Treg and IL-1 receptor type 2-expressing CD4+ T cell-deleted CD4+ T cell fraction prevents the progression of age-related hearing loss in a mouse model. J Neuroimmunol 2021; 357: 577628. doi: 10.1016/j.jneuroim.2021.577628. – reference: 30)Hwang JH, Chen JC, Hsu CJ, et al.: Plasma reactive oxygen species levels are correlated with severity of age-related hearing impairment in humans. Neurobiol Aging 2012; 33: 1920–1926. doi: 10.1016/j.neurobiolaging.2011.10.012. – reference: 1)Gates GA, Mills JH: Presbycusis. Lancet 2005; 366: 1111–1120. doi: 10.1016/S0140-6736(05)67423-5. |
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| SubjectTerms | ナイーブTリンパ球 免疫若返り 加齢性酸化慢性炎症 胸腺 骨髄移植 |
| Subtitle | 加齢性難聴の予防 |
| Title | 免疫老化阻止による抗加齢対策 |
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