Nothing Special   »   [go: up one dir, main page]
Skip to main content

Advertisement

Springer Nature Link
Log in

Role of Nrf2 in cell senescence regulation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Nuclear factor-E2-related factor 2 (Nrf2) is a key transcription factor known to be involved in maintaining cell redox balance and signal transduction and plays central role in reducing intracellular oxidative stress damage, delaying cell senescence and preventing age-related diseases. However, it has been shown that the level of Nrf2 decreases with age and that the silencing of the Nrf2 gene is associated with the induction of premature senescence. Therefore, a plethora of researchers have focused on elucidating the regulatory mechanism of Nrf2 in the prevention of cell senescence. This complex regulatory mechanism of Nrf2 in the cell senescence process involves coordinated regulation of multiple signaling molecules. After summarizing the function of Nrf2 and its relationship with cell senescence pathway, this review focuses on the recent advances and progress made in elucidating the regulatory mechanism of Nrf2 in the cell senescence process. Additionally, the information collected here may provide insights for further research on Nrf2, in particular, on its regulatory mechanism in the cell senescence process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Wan SY, Pan SY, Li B, Chen YM, Lin SL (2019) Rejuvenation: turning back the clock of aging kidney. J Formos Med Assoc. https://doi.org/10.1016/j.jfma.2019.05.020

    Article  Google Scholar 

  2. Lewis KN, Mele J, Hayes JD, Buffenstein R (2010) Nrf2, a guardian of healthspan and gatekeeper of species longevity. Integr Comp Biol 50:829–843. https://doi.org/10.1093/icb/icq034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rossman MJ, Kaplon RE, Hill SD, McNamara MN, Santos-Parker JR, Pierce GL, Seals DR, Donato AJ (2017) Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function. Am J Physiol Heart Circ Physiol 313:890–895. https://doi.org/10.1152/ajpheart.00416.2017

    Article  CAS  Google Scholar 

  4. Vilas JM, Carneiro C, Silva-Álvarez SD, Ferreirós A, González P, Gómez M, Ortega S, Serrano M, García-Caballero T, González-Barcia M (2018) Adult Sox2+ stem cell exhaustion in mice results in cellular senescence and premature aging. Aging Cell 17:e12834. https://doi.org/10.1111/acel.12834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Khemais-Benkhiat S, Belcastro E, Idris-Khodja N, Park SH, Amoura L, Abbas M, Auger C, Kessler L, Mayoux E, Toti F (2019) Angiotensin II-induced redox- sensitive SGLT1 and 2 expression promotes high glucose-induced endothelial cell senescence. J Cell Mol Med 24:2109–2122. https://doi.org/10.1111/jcmm.14233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sun Y, Zheng Y, Wang C, Liu Y (2018) Glutathione depletion induces ferroptosis, autophagy, and premature cell senescence in retinal pigment epithelial cells. Cell Death Dis 9:753. https://doi.org/10.1038/s41419-018-0794-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sun T, Yu HY, Zhang CL, Zhu TN, Huang SH (2018) Respiratory syncytial virus infection up-regulates TLR7 expression by inducing oxidative stress via the Nrf2/ARE pathway in A549 cells. Arch Virol 163:1209–1217. https://doi.org/10.11007/s00705-018-3739-4

    Article  CAS  PubMed  Google Scholar 

  8. Mirco M, Covi V, Tabaracci G, Malatesta M (2019) The role of Nrf2 in the antioxidant cellular response to medical ozone exposure. Int J Mol Sci 20:4009. https://doi.org/10.3390/ijms20164009

    Article  CAS  Google Scholar 

  9. Lewis KN, Wason E, Edrey YH, Kristan DM, Nevo E, Buffenstein R (2015) Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. Proc Natl Acad Sci 112:3722–3727. https://doi.org/10.1073/pnas.1417566112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tullet JMA, Green JW, Au C, Benedetto A, Thompson MA, Clark E, Gilliat AF, Young A, Schmeisser K, Gems D (2017) The SKN-1/Nrf2 transcription factor can protect against oxidative stress and increase lifespan in C. elegans by distinct mechanisms. Aging Cell 16:1191–1194. https://doi.org/10.1111/acel.12627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Silva-Palacios A, Ostolga-Chavarria M, Zazueta C, Königsberg M (2018) Nrf2: molecular and epigenetic regulation during aging. Ageing Res Rev 47:31–40. https://doi.org/10.1016/j.arr.2018.06.003

    Article  CAS  PubMed  Google Scholar 

  12. Corenblum MJ, Ray S, Remley QW, Long M, Harder B, Zhang DD, Barnes CA, Madhavan L (2016) Reduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period. Aging Cell 15:725–736. https://doi.org/10.1111/zcel.12482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gureev AP, Shaforostova EA, Popov VN (2019) Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1α signaling pathways. Front Genet 10:435. https://doi.org/10.3389/fgene.2019.00435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu J, Wang L, Wang Z, Liu JP (2019) Roles of telomere biology in cell senescence, replicative and chronological ageing. Cells. https://doi.org/10.3390/cells8010054

    Article  PubMed  PubMed Central  Google Scholar 

  15. Magalhães JPD, Passos JF (2018) Stress, cell senescence and organismal ageing. Mech Ageing Dev 170:2–9. https://doi.org/10.1016/j.mad.2017.07.001

    Article  CAS  PubMed  Google Scholar 

  16. Chapman J, Fielder E, Passos JF (2019) Mitochondrial dysfunction and cell senescence: deciphering a complex relationship. FEBS Lett 593:1566–1579. https://doi.org/10.1002/1873-3468.13498

    Article  CAS  PubMed  Google Scholar 

  17. Korolchuk VI, Miwa S, Carroll B, Von Zglinicki T (2017) Mitochondria in cell senescence: is mitophagy the weakest link? EBioMedicine 21:7–13. https://doi.org/10.1016/j.ebiom.2017.03.020

    Article  PubMed  PubMed Central  Google Scholar 

  18. Liu RM, Liu G (2020) Cell senescence and fibrotic lung diseases. Exp Gerontol 132:110836. https://doi.org/10.1016/j.exger.2020.110836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shimizu I, Minamino T (2020) Cellular senescence in arterial diseases. J Lipid Atheroscler 9:79–91. https://doi.org/10.12997/jla.2020.9.1.79

    Article  PubMed  PubMed Central  Google Scholar 

  20. Birch J, Barnes PJ, Passos JF (2017) Mitochondria, telomeres and cell senescence: implications for lung ageing and disease. Pharmacol Ther 183:34–49. https://doi.org/10.1016/j.pharmthera.2017.10.005

    Article  CAS  PubMed  Google Scholar 

  21. Wang Y, Chen Y, Guan L, Zhang H, Huang Y, Johnson CH, Wu Z, Gonzalez FJ, Yu A, Huang P (2018) Carnitine palmitoyltransferase 1C regulates cancer cell senescence through mitochondria-associated metabolic reprograming. Cell Death Differ 25:733–746. https://doi.org/10.1038/s41418-017-0013-3

    Article  CAS  PubMed Central  Google Scholar 

  22. Abbadie C, Pluquet O, Pourtier A (2017) Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses? Cell Mol Life Sci 74:4471–4509. https://doi.org/10.1007/s00018-017-2587-9

    Article  CAS  PubMed  Google Scholar 

  23. Tian Y, Li H, Qiu T, Dai J, Zhang Y, Chen J, Cai H (2019) Loss of PTEN induces lung fibrosis via alveolar epithelial cell senescence depending on NF-κB activation. Aging Cell 18:e12858. https://doi.org/10.1111/acel.12858

    Article  CAS  PubMed  Google Scholar 

  24. Herbig U, Jobling WA, Chen BPC, Chen DJ, Sedivy JM (2004) Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. Mol Cell 14:501–513. https://doi.org/10.1016/s1097-2765(04)00256-4

    Article  CAS  PubMed  Google Scholar 

  25. Kloska D, Kopacz A, Piechota-Polanczyk A, Nowak W, Dulak J, Jozkowicz A, Grochot-Przeczek A (2019) Nrf2 in aging—focus on the cardiovascular system. Vasc Phaemacol 112:42–53. https://doi.org/10.1016/j.vph.2018.08.009

    Article  CAS  Google Scholar 

  26. Stallone G, Infante B, Prisciandaro C, Grandaliano G (2019) mtor and aging: an old fashioned dress. Int J Mol Sci 20:2774. https://doi.org/10.3390/ijms20112774

    Article  CAS  PubMed Central  Google Scholar 

  27. Fettucciari K, Macchioni L, Davidescu M, Scarpelli P, Palumbo C, Corazzi L, Marchegiani A, Cerquetella M, Spaterna A, Marconi P (2018) Clostridium difficile toxin B induces senescence in enteric glial cells: a potential new mechanism of Clostridium difficile pathogenesis. Biochim Biophys Acta Mol Cell Res 1865:1945–1958. https://doi.org/10.1016/j.bbamcr.2018.10.007

    Article  CAS  PubMed  Google Scholar 

  28. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A (2016) Naturally occurring p16 Ink4a-positive cells shorten healthy lifespan. Nature 530:184–189. https://doi.org/10.1038/nature16932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang DG, Liu L, Zheng XY (2008) Cyclin-dependent kinase inhibitor p16INK4a and telomerase may co-modulate endothelial progenitor cells senescence. Ageing Res Rev 7:137–146. https://doi.org/10.1016/j.arr.2008.02.001

    Article  CAS  PubMed  Google Scholar 

  30. Berkenkamp B, Susnik N, Baisantry A, Kuznetsova I, Jacobi C, Sörensen-Zender I, Broecker V, Haller H, Melk A, Schmitt R (2014) In vivo and in vitro analysis of age-associated changes and somatic cellular senescence in renal epithelial cells. PLoS One 9:1–11. https://doi.org/10.1371/journal.pone.0088071

    Article  CAS  Google Scholar 

  31. Shin JM, Lee KM, Lee HJ, Yun JH, Nho CW (2019) Physalin A regulates the Nrf2 pathway through ERK and p38 for induction of detoxifying enzymes. BMC Complement Altern Med 19:101. https://doi.org/10.1186/s12906-019-2511-y

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zheng L, Wei H, Yu H, Xing Q, Zou Y, Zhou Y, Peng J (2018) Fish skin gelatin hydrolysate production by ginger powder induces glutathione synthesis to prevent hydrogen peroxide induced intestinal oxidative stress via the Pept1-p62-Nrf2 cascade. J Agric Food Chem 66:11601–11611. https://doi.org/10.1021/acs.jafc.8b02840

    Article  CAS  PubMed  Google Scholar 

  33. Wang Z, Han N, Zhao K, Li Y, Chi Y, Wang B (2019) Protective effects of pyrroloquinoline quinine against oxidative stress-induced cellular senescence and inflammation in human renal tubular epithelial cells via Keap1/Nrf2 signaling pathway. Int Immunpharmacol 72:445–453. https://doi.org/10.1016/j.intimp.2019.04.040

    Article  CAS  Google Scholar 

  34. Ishii T, Warabi E (2019) Mechanism of rapid nuclear factor-E2-related factor 2 (Nrf2) activation via membrane-associated estrogen receptors: roles of NADPH oxidase 1, neutral sphingomyelinase 2 and epidermal growth factor receptor (EGFR). Antioxidants 8:69. https://doi.org/10.3390/antiox8030069

    Article  CAS  PubMed Central  Google Scholar 

  35. Ji S, Zheng Z, Liu S, Ren G, Gao J, Zhang Y, Li G (2018) Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence in cancer cells. Exp Cell Res 370:292–302. https://doi.org/10.1016/j.yexcr.2018.06.031

    Article  CAS  PubMed  Google Scholar 

  36. Chen L, Yang R, Qiao W, Zhang W, Chen J, Mao L, Goltzman D, Miao D (2019) 1,25-Dihydroxyvitamin D exerts an antiaging role by activation of Nrf2-antioxidant signaling and inactivation of p16/p53-senescence signaling. Aging Cell 18:e12951. https://doi.org/10.1111/acel.12951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liao N, Shi Y, Zhang C, Zheng Y, Wang Y, Zhao B, Zeng Y, Liu X, Liu J (2019) Antioxidants inhibit cell senescence and preserve stemness of adipose tissue-derived stem cells by reducing ROS generation during long-term in vitro expansion. Stem Cell Res Ther 10:1–11. https://doi.org/10.1186/s13287-019-1404-9

    Article  CAS  Google Scholar 

  38. Sun Z, Huang Z, Zhang DD (2009) Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response. PLoS One 4:1–9. https://doi.org/10.1371/journal.pone.0006588

    Article  CAS  Google Scholar 

  39. Zhang DD (2010) The Nrf2-Keap1-ARE signaling pathway: the regulation and dual function of Nrf2 in cancer. Antioxid Redox Signal 13:1623–1626. https://doi.org/10.1089/ars.2010.3301

    Article  CAS  PubMed  Google Scholar 

  40. O’Connell MA, Hayes JD (2015) The Keap1/Nrf2 pathway in health and disease: from the bench to the clinic. Biochem Soc Trans 43:687–689. https://doi.org/10.1042/BST20150069

    Article  CAS  PubMed  Google Scholar 

  41. Lau A, Wang XJ, Zhao F, Villeneuve NF, Wu T, Jiang T, Sun Z, White E, Zhang DD (2010) A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol 30:3275–3285. https://doi.org/10.1128/MCB.00248-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kuosmanen SM, Sihvola V, Kansanen E, Kaikkonen MU, Levonen AL (2018) MicroRNAs mediate the senescence-associated decline of NRF2 in endothelial cells. Redox Biol 18:77–83. https://doi.org/10.1016/j.redox.2018.06.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bellezza I, Giambanco I, Minelli A, Donato R (2018) Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res 1865:721–733. https://doi.org/10.1016/j.bbamcr.2018.02.010

    Article  CAS  PubMed  Google Scholar 

  44. Kopacz A, Klóska D, Proniewski B, Cysewski D, Personnic N, Piechota-Polańczyk A et al (2019) Keap1 controls protein S-nitrosation and apoptosis-senescence switch in endothelial cells. Redox Biol 28:101304. https://doi.org/10.1016/j.redox.2019.101304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kapeta S, Chondrogianni N, Gonos ES (2010) Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts. J Biol Chem 285:8171–8184. https://doi.org/10.1074/jbc.M109.031575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang RY, Liu LH, Liu H, Wu KF, An J, Wang Q, Liu Y, Bai LJ, Qi BM, Qi BL, Zhang L (2018) Nrf2 protects against diabetic dysfunction of endothelial progenitor cells via regulating cell senescence. Int J Mol Med 42:1327–1340. https://doi.org/10.3892/ijmm.2018.3727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, Caples K et al (2017) Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. Aging Cell 16:564–574. https://doi.org/10.1111/acel.12587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW (2016) Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell 15:872–884. https://doi.org/10.1111/acel.12496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fang J, Yan Y, Teng X, Wen X, Li N, Peng S, Liu W, Donadeu FX, Zhao S, Hua J (2018) Melatonin prevents senescence of canine adipose-derived mesenchymal stem cells through activating NRF2 and inhibiting ER stress. Aging 10:2954–2972. https://doi.org/10.18632/aging.101602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang J, Guo HM (2019) Astragaloside IV ameliorates high glucose-induced HK-2 cell apoptosis and oxidative stress by regulating the Nrf2/ARE signaling pathway. Exp Ther Med 17:4409–4416. https://doi.org/10.3892/etm.2019.7495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Itoh K, Mimura J, Yamamoto M (2010) Discovery of the negative regulator of Nrf2, Keap1: a historical overview. Antioxid Redox Signal 13:1665–1678. https://doi.org/10.1089/ars.2010.3222

    Article  CAS  PubMed  Google Scholar 

  52. Tu W, Wang H, Li S, Liu Q, Sha H (2019) The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis 10:637–651. https://doi.org/10.14336/AD.2018.0513

    Article  PubMed  PubMed Central  Google Scholar 

  53. Keum YS, Choi BY (2014) Molecular and chemical regulation of the Keap1-Nrf2 signaling pathway. Molecules 19:10074–10089. https://doi.org/10.3390/molecules190710074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Chen W, Sun Z, Wang XJ, Jiang T, Huang Z, Fang D, Zhang DD (2009) Direct interaction between Nrf2 and p21Cip1/WAF1 upregulates the Nrf2-mediated antioxidant response. Mol cell 34:663–673. https://doi.org/10.1016/j.molcel.2009.04.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A et al (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Bio 12:213–223. https://doi.org/10.1038/ncb2021

    Article  CAS  Google Scholar 

  56. Yang G, Zhao K, Ju Y, Mani S, Cao Q, Puukila S, Khaper N, Wu L, Wang R (2013) Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2. Antioxid Redox Signal 18:1906–1919. https://doi.org/10.1089/ars.2012.4645

    Article  CAS  PubMed  Google Scholar 

  57. Chiang MC, Nicol CJ, Cheng YC (2018) Resveratrol activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against amyloid-beta-induced inflammation and oxidative stress. Neurochem Int 115:1–10. https://doi.org/10.1016/j.neuint.2017.10.002

    Article  CAS  PubMed  Google Scholar 

  58. Park SY, Choi MH, Park G, Choi YW (2018) Petasites japonicus bakkenolide B inhibits lipopolysaccharide-induced pro-inflammatory cytokines via AMPK/Nrf2 induction in microglia. Int J Mol Med 41:1683–1692. https://doi.org/10.3892/ijmm.2017.3350

    Article  CAS  PubMed  Google Scholar 

  59. Jiang P, Du W, Mancuso A, Wellen KE, Yang X (2013) Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493:689–693. https://doi.org/10.1038/nature11776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ido Y, Duranton A, Lan F, Weikel KA, Breton L, Ruderman NB (2015) Resveratrol prevents oxidative stress-induced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes. Plos One 10:1–18. https://doi.org/10.1371/journal.pone.0115341

    Article  CAS  Google Scholar 

  61. Salminen A, Kauppinen A, Kaarniranta K (2019) AMPK activation inhibits the functions of myeloid-derived suppressor cells (MDSC): impact on cancer and aging. J Mol Med 97:1049–1064. https://doi.org/10.1007/s00109-019-01795-9

    Article  CAS  PubMed  Google Scholar 

  62. Jang HJ, Yang KE, Oh WK, Lee SI, Hwang IH, Ban KT, Yoo HS, Choi JS, Yeo EJ, Jang IS (2019) Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels. Aging 11:3731–3749. https://doi.org/10.18632/aging.102013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Karnewar S, Neeli PK, Panuganti D, Kotagiri S, Mallappa S, Jain N, Jerald MK, Kotamraju S (2018) Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: relevance in age-associated vascular dysfunction. Biochim Biophys Acta Mol Basis Dis 1864:1115–1128. https://doi.org/10.1016/j.bbadis

    Article  CAS  PubMed  Google Scholar 

  64. Li R, Liu Y, Shan YG, Gao L, Wang F, Qiu CG (2019) Bailcalin protects against diabetic cardiomyopathy through Keap1/Nrf2/AMPK-mediated antioxidative and lipid-lowering effects. Oxid Med Cell Longev. https://doi.org/10.1155/2019/3206542

    Article  PubMed  PubMed Central  Google Scholar 

  65. Yang Q, Han L, Li J, Xu H, Liu X, Wang X, Pan C, Lei C, Chen H, Lan X (2019) Activation of Nrf2 by phloretin attenuates palmitic acid-induced endothelial cell oxidative stress via AMPK-dependent signaling. J Agric Food Chem 67:120–131. https://doi.org/10.1021/acs.jafc.8b05025

    Article  CAS  PubMed  Google Scholar 

  66. Wang Z, Chen Z, Jiang Z, Luo P, Liu L, Huang Y, Wang H et al (2019) Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents. Nat Commun 10:2538. https://doi.org/10.1038/s41467-019-10386-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Li J, Zheng X, Ma X, Xu X, Du Y, Lv Q, Li X, Wu Y, Sun H, Yu L, Zhang Z (2019) Melatonin protects against chromium (VI)-induced cardiac injury via activating the AMPK/Nrf2 pathway. J Inorg Biochem. https://doi.org/10.1016/j.jinorgbio.2019.110698

    Article  PubMed  PubMed Central  Google Scholar 

  68. Liu L, Wu W, Li J, Jiao WH, Liu LY, Tang J, Liu L, Sun F, Han BN, Lin HW (2018) Two sesquiterpene aminoquinones protect against oxidative injury in HaCaT keratinocytes via activation of AMPKα/ERK-Nrf2/ARE/HO-1 signaling. Biomed Pharmacother 100:417–425. https://doi.org/10.1016/j.biopha.2018.02.034

    Article  CAS  PubMed  Google Scholar 

  69. Fan L, Yin S, Zhang E, Hu H (2018) Role of p62 in the regulation of cell death induction. Apoptosis 23:187–193. https://doi.org/10.1007/s10495-018-1445-z

    Article  CAS  PubMed  Google Scholar 

  70. Sánchez-Martín P, Sou YS, Kageyama S, Koike M, Waguri S, Komatsu M (2020) NBR1- mediated p62-liquid droplets enhance the Keap1-Nrf2 system. EMBO Rep. https://doi.org/10.15252/embr.201948902

    Article  PubMed  PubMed Central  Google Scholar 

  71. Bjørkøy G, Lamark T, Johansen T (2006) p62/SQSTM1: a missing link between protein aggregates and the autophagy machinery. Autophagy 2:138–139. https://doi.org/10.4161/auto.2.2.2405

    Article  PubMed  Google Scholar 

  72. Masuda GO, Yashiro M, Kitayamak MY et al (2016) Clinicopathological correlations of autophagy-related proteins LC3, beclin 1 and p62 in gastric cancer. Anticancer Res 36:129–136

    CAS  PubMed  Google Scholar 

  73. García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J et al (2016) Autophagy maintains stemness by preventing senescence. Nature 529:37–42. https://doi.org/10.1038/nature16187

    Article  CAS  PubMed  Google Scholar 

  74. Zhao Y, Song W, Wang Z, Wang Z, Jin X, Xu J, Bai L, Li Y, Cui J, Cai L (2018) Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: role of Akt- mediated Nrf2 activation and p62-dependent Keap1 degradation. Redox Biol 14:609–617. https://doi.org/10.1016/j.redox.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  75. Kageyama S, Saito T, Obata M, Koide RH, Ichimura Y, Komatsu M (2018) Negative regulation of the Keap1-Nrf2 pathway by a p62/Sqstm1 splicing variant. Mol Cell Biol. https://doi.org/10.1128/MCB.00642-17

    Article  PubMed  PubMed Central  Google Scholar 

  76. Komatsu M, Ichimura Y (2010) Physiological significance of selective degradation of p62 by autophagy. FEBS Lett 584:1374–1378. https://doi.org/10.1016/j.febslet.2010.02.017

    Article  CAS  PubMed  Google Scholar 

  77. Gilardini Montani MS, Cecere N, Granato M, Romeo MA, Falcinelli L, Ciciarelli U, D’Orazi G, Faggioni A, Cirone M (2019) Mutant p53, stabilized by its interplay with HSP90, activates a positive feed-back loop between NRF2 and p62 that induces chemo-resistance to apigenin in pancreatic cancer cells. Cancers 11:703. https://doi.org/10.3390/cancers11050703

    Article  CAS  PubMed Central  Google Scholar 

  78. Song X, Yin S, Huo Y, Liang M, Fan L, Ye M, Hu H (2015) Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy. Free Radic Biol Med 89:135–146. https://doi.org/10.1016/j.freeradbiomed.2015.07.006

    Article  CAS  PubMed  Google Scholar 

  79. Ji LL, Sheng YC, Zheng ZY, Shi L, Wang ZT (2015) The involvement of p62-Keap1-Nrf2 antioxidative signaling pathway and JNK in the protection of natural flavonoid quercetin against hepatotoxicity. Free Radic Biol Med 85:12–33. https://doi.org/10.1016/j.freeradbiomed.2015.03.035

    Article  CAS  PubMed  Google Scholar 

  80. Xia MH, Yan XY, Zhou L, Xu L, Zhang LC, Yi HW, Su J (2020) p62 suppressed VK3-induced oxidative damage through Keap1/Nrf2 pathway in human ovarian cancer cells. J Cancer 11:1299–1307. https://doi.org/10.7150/jca.34423.eCollection

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ichimura Y, Wanguri S, Sou Y, Kageyama S et al (2013) Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol Cell 51:618–631. https://doi.org/10.1016/j.molcel.2013.08.003

    Article  CAS  PubMed  Google Scholar 

  82. Zhou X, Chen Z, Zhong W, Yu R, He L (2019) Effect of fluoride on PERK-Nrf2 signaling pathway in mouse ameloblasts. Hum Exp Toxicol 38:833–845. https://doi.org/10.1177/0960327119842273

    Article  CAS  PubMed  Google Scholar 

  83. Cormenier J, Martin N, Deslé J, Salazar-Cardozo C, Pourtier A, Abbadie C, Pluquet O (2019) The ATF6α arm of the unfolded protein response mediates replicative senescence in human fibroblasts through a cox2/prostaglandin e2 intracrine pathway. Mech Aging Dev 170:82–91. https://doi.org/10.1016/j.mad.2017.08.003

    Article  CAS  Google Scholar 

  84. Huang T, Zhao J, Guo D, Pang H, Zhao Y, Song J (2019) Curcumin mitigates axonal injury and neuronal cell apoptosis through the PERK/Nrf2 signaling pathway following diffuse axonal injury. Neuroreport 29:661–677. https://doi.org/10.1097/WNR.0000000000001015

    Article  CAS  Google Scholar 

  85. Chen S, Wang X, Nisar MF, Lin M, Zhong JL (2019) Heme oxygenases: cellular multifunctional and protective molecules against UV-induced oxidative stress. Oxid Med Cell Longev 2019:5416728. https://doi.org/10.1155/2019/5416728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Romine LC, Wiseman RL (2019) PERK signaling regulates extracellular proteostasis of an amyloidogenic protein during endoplasmic reticulum stress. Sci Rep 9:410. https://doi.org/10.1038/s41598-018-37207-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Tao T, Wang J, Wang X, Wang Y, Mao H, Liu X (2019) The PERK/Nrf2 pathway mediates endoplasmic reticulum stress-induced injury by upregulating endoplasmic reticulophagy in H9c2 cardiomyoblasts. Life Sci. https://doi.org/10.1016/j.lfs.2019.116944

    Article  PubMed  Google Scholar 

  88. Yang X, Yao W, Liu H, Gao Y, Liu R, Xu L (2017) Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway. Sci Rep. https://doi.org/10.1038/s41598-017-00936-9

    Article  PubMed  PubMed Central  Google Scholar 

  89. Wang J, Hu X, Jiang H (2016) ERS-PERK signaling pathway-mediated Nrf2/ ARE-HO-1 axis: a novel therapeutic target for attenuating myocardial ischemia and reperfusion injury. Int J Cardiol 203:779–780. https://doi.org/10.1016/j.ijcard.2015.11.033

    Article  PubMed  Google Scholar 

  90. Liu J, Du L (2015) PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes. Biochem Biophys Res Commun 467:197–203. https://doi.org/10.1016/j.bbrc.2015.10.007

    Article  CAS  PubMed  Google Scholar 

  91. Zhu YF, Li XH, Yuan ZP, Li CY, Tian RB, Jia W, Xiao ZP (2015) Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway. Eur J Pharmacol 762:239–246. https://doi.org/10.1016/j.ejphar.2015.06.002

    Article  CAS  PubMed  Google Scholar 

  92. Amodio G, Moltedo O, Fasano D, Zerillo L, Oliveti M et al (2019) PERK-mediated unfolded protein response activation and oxidative stress in PARK20 fibroblasts. Front Neurosci 13:2019. https://doi.org/10.3389/fnins.2019.00673.eCollection

    Article  Google Scholar 

  93. Zheng W, Xie W, Yin D, Luo R, Liu M, Guo F (2019) ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell Commun Signal 17:42. https://doi.org/10.1186/s12964-019-0353-3

    Article  PubMed  PubMed Central  Google Scholar 

  94. Sun J, Yu X, Huangpu H, Yao F (2019) Ginsenoside Rb3 protects cardiomyocytes against hypoxia/reoxygenation injury via activating the antioxidation signaling pathway of PERK/Nrf2/HMOX1. Biomed Pharmacother 109:254–261. https://doi.org/10.1016/j.biopha.2018.09.002

    Article  CAS  PubMed  Google Scholar 

  95. Liang Y, Fan C, Yan X, Lu X, Jiang H, Di S, Ma A, Feng Y, Zhang Z, Feng P (2019) Berberine ameliorates lipopolysaccharide-induced acute lung injury via the PERK-mediated Nrf2/HO-1 signaling axis. Phytother Res 33:130–148. https://doi.org/10.1002/ptr.6206

    Article  CAS  PubMed  Google Scholar 

  96. Cao D, Zhao M, Wan C, Zhang Q, Tang T, Liu J, Shao Q, Yang B, He J, Jiang C (2019) Role of tea polyphenols in delaying hyperglycemia-induced senescence in human glomerular mesangial cells via miR-126/Akt-p53-p21 pathways. Int Urol Nephrol 51:1071–1078. https://doi.org/10.1007/s11255-019-02165-7

    Article  CAS  PubMed  Google Scholar 

  97. Johnson ACM, Zager RA (2018) Mechanisms and consequences of oxidant- induced renal preconditioning: an Nrf2-dependent, P21-independent, anti-senescence pathway. Nephrol Dial Transplant 33:1927–1941. https://doi.org/10.1093/ndt/gfy029

    Article  CAS  PubMed  Google Scholar 

  98. Yuan L, Du X, Tang S, Wu S, Wang L, Xiang Y, Qu X, Liu H, Qin X, Liu C (2019) ITGB 4 deficiency induces senescence of airway epithelial cells through p53 activation. FEBS J 286:1191–1203. https://doi.org/10.1111/febs.14749

    Article  CAS  PubMed  Google Scholar 

  99. Muhlinen NV, Horikawa I, Alam F, Isogaya K, Lissa D, Vojtesek B, Lane DP, Harris CC (2018) p53 isoforms regulate premature aging in human cells. Oncogene 37:2379–2393. https://doi.org/10.1038/s41388-017-0101-3

    Article  CAS  Google Scholar 

  100. Georgakilas AG, Martin OA, Bonner WM (2017) p21: a two-faced genome guardian. Trends Mol Med 23:310–319. https://doi.org/10.1016/j.molmed.2017.02.001

    Article  CAS  PubMed  Google Scholar 

  101. Zhang W, Huang C, Sun A, Qiao L, Zhang X, Huang J, Sun X, Yang X, Sun S (2018) Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo. Biomed Pharmacother 106:1126–1134. https://doi.org/10.1016/j.biopha.2018.07.020

    Article  CAS  PubMed  Google Scholar 

  102. Yang F, Yi M, Liu Y, Wang Q, Hu Y, Deng H (2018) Glutaredoxin-1 silencing induces cell senescence via p53/p21/p16 signaling axis. J Proteome Res 17:1091–1100. https://doi.org/10.1021/acs.jproteome.7b00761

    Article  CAS  PubMed  Google Scholar 

  103. Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705. https://doi.org/10.1146/annurev-physiol-030212-183653

    Article  CAS  PubMed  Google Scholar 

  104. Ma F, Wu J, Jiang Z, Huang W, Jia Y, Sun W, Wu H (2019) P53/NRF2 mediates SIRT1’s protective effect on diabetic nephropathy. Biochim Biophys Acta Mol Cell Res 1866:1272–1281. https://doi.org/10.1016/j.bbamcr.2019.04.006

    Article  CAS  PubMed  Google Scholar 

  105. Faraonio R, Vergara P, Marzo DD, Pierantoni MG, Napolitano M, Russo T, Cimino F (2006) p53 suppresses the Nrf2-dependent transcription of antioxidant response genes. J Biol Chem 281:39776–39784. https://doi.org/10.1074/jbc.M605707200

    Article  CAS  PubMed  Google Scholar 

  106. Kang KA, Piao MJ, Hyun YJ, Zhen AX, Cho SJ, Ahn MJ, Yi JM, Hyun JW (2019) Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells. Exp Mol Med 51:40. https://doi.org/10.1038/s12276-019-0238-y

    Article  CAS  PubMed Central  Google Scholar 

  107. Bose P, Siddique MUM, Acharya R, Jayaprakash V, Sinha BN, Lapenna A, Pattanayak SP (2020) Quinazolinone derivative BNUA-3 ameliorated [NDEA+ 2-AAF]-induced liver carcinogenesis in SD rats by modulating AhR-CYP1B1-Nrf2-Keap1 pathway. Clin Exp Pharmacol Physiol 47:143–157. https://doi.org/10.1111/1440-1681.13184

    Article  CAS  PubMed  Google Scholar 

  108. Ren F, Ji C, Huang Y, Aniagu S, Jiang Y, Chen T (2019) AHR-mediated ROS production contributes to the cardiac developmental toxicity of PM2.5 in zebrafish embryos. Sci Total Environ 719:135097. https://doi.org/10.1016/j.scitotenv.2019.135097

    Article  CAS  PubMed  Google Scholar 

  109. Neavin DR, Liu D, Ray B, Weinshilboum RM (2018) The role of the aryl hydrocarbon receptor (AHR) in immune and inflammatory diseases. Int J Mol Sci 19:3951. https://doi.org/10.3390/ijms19123851

    Article  CAS  Google Scholar 

  110. Bock KW (2018) From TCDD-mediated toxicity to searches of physiologic AHR functions. Biochem Pharmacol 155:419–424. https://doi.org/10.1016/j.bcp.2018.07.032

    Article  CAS  PubMed  Google Scholar 

  111. Fan Y, Boivin GP, Knudsen ES, Nebert DW, Xia Y, Puga A (2010) The aryl hydrocarbon receptor functions as a tumor suppressor of liver carcinogenesis. Cancer Res 70:212–220. https://doi.org/10.1158/0008-5472.CAN-09-3090

    Article  CAS  PubMed  Google Scholar 

  112. Koizumi M, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T (2014) Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells. J Atheroscler Thromb 21(9):906–916. https://doi.org/10.5551/jat.23663

    Article  Google Scholar 

  113. Bock KW (2019) Human AHR functions in vascular tissue: Pro-and anti-inflammatory responses of AHR agonists in atherosclerosis. Biochem pharmacol 159:116–120. https://doi.org/10.1016/j.bcp.2018.11.021

    Article  CAS  PubMed  Google Scholar 

  114. Bock KW (2019) Aryl hydrocarbon receptor (AHR) functions in NAD+ metabolism, myelopoiesis and obesity. Biochem Pharmacol 163:128–132. https://doi.org/10.1016/j.bcp.2019.02.021

    Article  CAS  PubMed  Google Scholar 

  115. Miao W, Hu L, Scrivens PJ, Batist G (2005) Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway. J Biol Chem 280:20340–20348. https://doi.org/10.1074/jbc.M412081200

    Article  CAS  PubMed  Google Scholar 

  116. Wakabayashi N, Slocum SL, Skoko JJ, Shin S, Kensler TW (2010) When NRF2 talks, who’s listening? Antioxid Redox Signal 13:1649–1663. https://doi.org/10.1089/ars.2010.3216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Łapczuk-Romańska J, Wajda A, Pius-Sadowska E, Kurzawski M, Niedzielski A, Machaliński B, Droździk M (2018) Effects of simvastatin on nuclear receptors, drug metabolizing enzymes and transporters expression in human umbilical vein endothelial cells. Pharmacol Rep 70:875–880. https://doi.org/10.1016/j.pharep.2018.03.008

    Article  CAS  PubMed  Google Scholar 

  118. Fuyuno Y, Uchi H, Yasumatsu M, Morino-Koga S, Tanaka Y, Mitoma C, Furue M (2018) Perillaldehyde inhibits AHR signaling and activates NRF2 antioxidant pathway in human keratinocytes. Oxid Med Cell Longev. https://doi.org/10.1155/2018/6091947

    Article  PubMed  PubMed Central  Google Scholar 

  119. Takei K, Hashimoto-Hachiya A, Takahara M, Tsuji G, Nakahara T, Furue M (2015) Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway. Toxicol Lett 234:74–80. https://doi.org/10.1016/j.toxlet.2015.02.007

    Article  CAS  PubMed  Google Scholar 

  120. Burton DG, Faragher RG (2018) Obesity and type-2 diabetes as inducers of premature cellular senescence and ageing. Biogerontology 19:447–459. https://doi.org/10.1007/s10522-018-9763-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wallach D, Kang TB, Kovalenko A (2014) Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol 14:51–59. https://doi.org/10.1038/nri3561

    Article  CAS  PubMed  Google Scholar 

  122. Zhao K, Wen L (2018) DMF attenuates cisplatin-induced kidney injury via activating Nrf2 signaling pathway and inhibiting NF-kB signaling pathway. Eur Rev Med Pharmacol Sci 22:8924–8931. https://doi.org/10.26355/eurrev-201812-16662

    Article  CAS  PubMed  Google Scholar 

  123. Gilmore TD (2006) Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25:6680–6684. https://doi.org/10.1038/sj.onc.1209954

    Article  CAS  PubMed  Google Scholar 

  124. Patil P, Niedernhofer LJ, Robbins PD, Lee J, Sowa G, Vo N (2018) Cellular senescence in intervertebral disc aging and degeneration. Curr Mol Biol Rep 4:180–190. https://doi.org/10.1007/s40610-018-0108-8

    Article  PubMed  PubMed Central  Google Scholar 

  125. Pahl HL (1999) Activators and target genes of Rel/NF-κB transcription factors. Oncogene 18:6853–6866. https://doi.org/10.1038/sj.onc.1203239

    Article  CAS  PubMed  Google Scholar 

  126. Sivandzade F, Prasad S, Bhalerao A, Cucullo L (2019) NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches. Redox Biol 21:101059. https://doi.org/10.1016/j.redox.2018.11.017

    Article  CAS  PubMed  Google Scholar 

  127. El-Shitany NA, Eid BG (2019) Icariin modulates carrageenan-induced acute inflammation through HO-1/Nrf2 and NF-kB signaling pathways. Biomed Pharmacother 120:109567. https://doi.org/10.1016/j.biopha.2019.109567

    Article  CAS  PubMed  Google Scholar 

  128. Kagama S, Natsuizaka M, Whelan KA, Facompre N et al (2015) Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene 34:2347–2359. https://doi.org/10.1038/onc.2014.169

    Article  CAS  Google Scholar 

  129. Zhang Y, Lian JB, Stein JL, Wijnen AJV, Stein GS (2009) The notch-responsive transcription factor Hes-1 attenuates osteocalcin promoter activity in osteoblastic cells. J Cell Biochem 108:651–659. https://doi.org/10.1002/jcb.22299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Dai C, Li B, Zhou Y, Li D, Zhang S, Li H, Xiao X, Tang S (2016) Curcumin attenuates quinocetone induced apoptosis and inflammation via the opposite modulation of Nrf2/HO-1 and NF-kB pathway in human hepatocyte L02 cells. Food Chem Toxicol 95:52–63. https://doi.org/10.1016/j.fct.2016.06.025

    Article  CAS  PubMed  Google Scholar 

  131. Ferrari D, Speciale A, Cristani M, Fratantonio D, Molonia MS, Ranaldi G, Saijia A, Cimino F (2016) Cyanidin-3-O-glucoside inhibits NF-KB signalling in intestinal epithelial cells exposed to TNF-α and exerts protective effects via Nrf2 pathway activation. Toxicol Lett 264:51–58. https://doi.org/10.1016/j.toxlet.2016.10.014

    Article  CAS  PubMed  Google Scholar 

  132. Xu Y, Yuan H, Luo Y, Zhao YJ, Xiao JH (2020) Ganoderic acid protects human amniotic mesenchymal stem cells against oxidative stress induced senescence through the PERK/NRF2 signaling pathway. Oxid Med Cell Longev 2020:8291413. https://doi.org/10.1155/2020/8291413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Bansal A, Simon MC (2018) Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 217:2291–2298. https://doi.org/10.1083/jcb.201804161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Lignitto L, LeBoeuf SE, Homer H et al (2019) Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1. Cell 178:316–329. https://doi.org/10.1016/j.cell.2019.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wiel C, Gal KL, Ibrahim MX et al (2019) BACH1 stabilization by antioxidants stimulates lung cancer metastasis. Cell 178:330–345. https://doi.org/10.1016/j.cell.2019.06.005

    Article  CAS  PubMed  Google Scholar 

  136. Xu X, Liu C, Li Z, Gai C et al (2020) Regulation of GSK3β/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer. Mol Cell Biochem. https://doi.org/10.1007/s11010-020-03821-8

    Article  PubMed  Google Scholar 

  137. Diane E, Hanay LJ (2017) Responses to reductive stress in the cardiovascular system. Free Radic Biol Med 109:114–124. https://doi.org/10.1016/j.freeradbiomed.2016.12.006

    Article  CAS  Google Scholar 

  138. Zucker SN, Fink EE, Bagati A, Mannava S et al (2014) Nrf2 amplifies oxidative stress via induction of Klf9. Mol Cell 53:916–928. https://doi.org/10.1016/j.molcel.2014.01.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Bellezza I, Riuzzi F, Chiappalupi S, Arcuri C et al (2020) Reductive stress in striated muscle cells. Cell Mol Life Sci. https://doi.org/10.1007/s00018-020-03476-0

    Article  PubMed  Google Scholar 

  140. Rajasekaran NS, Shelar SB, Jones DP, Hodial JR (2020) Reductive stress impairs myogenic differentiation. Redox Biol 34:101492. https://doi.org/10.1016/j.redox.2020.101492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors are grateful to financial support from National Natural Science Foundation of China (No. 31960191), Science and Technology Innovation Leading Academics of National High-level Personnel of Special Support Program (GKFZ-2018-29), Guizhou High-Level Innovative Talent Support Program (No. QKH-RC-20154028), and S&T Foundation of Guizhou (No. QKH-2017-1422).

Author information

Authors and Affiliations

  1. Zunyi Municiptal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China

    Huan Yuan, Yan Xu, Yi Luo, Nuo-Xin Wang & Jian-Hui Xiao

  2. Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, People’s Republic of China

    Yan Xu, Yi Luo, Nuo-Xin Wang & Jian-Hui Xiao

  3. Zunyi Municiptal Key Laboratory of Medicinal Biotechnology, Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563003, People’s Republic of China

    Jian-Hui Xiao

Authors
  1. Huan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nuo-Xin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Hui Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HY: reviewed the literature, writing of original draft; YX & YL & NXW: revised the manuscript; JHX: conceptualization, supervision, and critical revision and final approval of manuscript.

Corresponding author

Correspondence to Jian-Hui Xiao.

Ethics declarations

Conflicts of interest

The authors confirm that there are no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuan, H., Xu, Y., Luo, Y. et al. Role of Nrf2 in cell senescence regulation. Mol Cell Biochem 476, 247–259 (2021). https://doi.org/10.1007/s11010-020-03901-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03901-9

Keywords

Search

Navigation