Abstract
Review paper attempts to explain the dynamic aspects of redox signaling in aging through autophagy, inflammation, and senescence. It begins with ROS source in the cell, then states redox signaling in autophagy, and regulation of autophagy in aging. Next, we discuss inflammation and redox signaling with various pathways involved: NOX pathway, ROS production via TNF-α, IL-1β, xanthine oxidase pathway, COX pathway, and myeloperoxidase pathway. Also, we emphasize oxidative damage as an aging marker and the contribution of pathophysiological factors to aging. In senescence-associated secretory phenotypes, we link ROS with senescence, aging disorders. Relevant crosstalk between autophagy, inflammation, and senescence using a balanced ROS level might reduce age-related disorders. Transducing the context-dependent signal communication among these three processes at high spatiotemporal resolution demands other tools like multi-omics aging biomarkers, artificial intelligence, machine learning, and deep learning. The bewildering advancement of technology in the above areas might progress age-related disorders diagnostics with precision and accuracy.
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References
Acosta JC, O’Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:1006–1018. https://doi.org/10.1016/J.CELL.2008.03.038
Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990. https://doi.org/10.1038/NCB2784
Aiken CT, Kaake RM, Wang X, Huang L (2011) Oxidative stress-mediated regulation of proteasome complexes. Mol Cell Proteomics. https://doi.org/10.1074/mcp.M110.006924
Allsopp RC, Vaziri H, Patterson C et al (1992) Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 89:10114–10118. https://doi.org/10.1073/PNAS.89.21.10114
Aman Y, Schmauck-Medina T, Hansen M et al (2021) Autophagy in healthy aging and disease. Nat Aging 1:634–650. https://doi.org/10.1038/s43587-021-00098-4
Anerillas C, Abdelmohsen K, Gorospe M (2020) Regulation of senescence traits by MAPKs. GeroScience 42:397–408. https://doi.org/10.1007/s11357-020-00183-3
Aslam M, Ladilov Y (2022) Emerging role of cAMP/AMPK signaling. Cells 11:308. https://doi.org/10.3390/cells11020308
Atayik MC, Çakatay U (2022) Mitochondria-targeted senotherapeutic interventions. Biogerontology 23:401–423. https://doi.org/10.1007/s10522-022-09973-y
Atayik MC, Yanar K, Çakatay U (2022) Redox proteostasis in subcellular aging. In: Çakatay U (ed) Redox signaling and biomarkers in ageing. Springer International Publishing, Cham, pp 209–228
Azzi A (2022) Oxidative stress: what is it? Can it be measured? Where is it located? Can it be good or bad? Can it be prevented? Can it be cured? Antioxidants (Basel) 11:1431. https://doi.org/10.3390/antiox11081431
Baar MP, Brandt RMC, Putavet DA et al (2017) Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169:132-147e16. https://doi.org/10.1016/J.CELL.2017.02.031
Baker DJ, Wijshake T, Tchkonia T et al (2011) Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479:232–236. https://doi.org/10.1038/NATURE10600
Barnig C, Bezema T, Calder PC et al (2019) Activation of resolution pathways to prevent and fight chronic inflammation: lessons from asthma and inflammatory bowel disease. Front Immunol 10:1699
Bartolini D, Dallaglio K, Torquato P et al (2018) Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. Transl Res 193:54–71. https://doi.org/10.1016/j.trsl.2017.11.007
Bayat H, Schröder K, Pimentel DR et al (2012) Activation of thromboxane receptor modulates interleukin-1β-induced monocyte adhesion—a novel role of Nox1. Free Radic Biol Med 52:1760–1766. https://doi.org/10.1016/j.freeradbiomed.2012.02.052
Bedard K, Krause K-H (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313. https://doi.org/10.1152/physrev.00044.2005
Bhaumik D, Scott GK, Schokrpur S et al (2009) MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging 1:402–411. https://doi.org/10.18632/AGING.100042
Birch J, Passos JF (2017) Targeting the SASP to combat ageing: mitochondria as possible intracellular allies? BioEssays. https://doi.org/10.1002/BIES.201600235
Birch-Machin MA, Bowman A (2016) Oxidative stress and ageing. Br J Dermatol 175 Suppl 2:26–29. https://doi.org/10.1111/bjd.14906
Blackburn EH, Epel ES, Lin J (2015) Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science (New York NY) 350:1193–1198. https://doi.org/10.1126/SCIENCE.AAB3389
Boťanská B, Dovinová I, Barančík M (2022) The interplay between autophagy and redox signaling in cardiovascular diseases. Cells 11:1203. https://doi.org/10.3390/cells11071203
Budhu A, Wang XW (2006) The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 80:1197–1213. https://doi.org/10.1189/jlb.0506297
Burton DGA, Matsubara H, Ikeda K (2010) Pathophysiology of vascular calcification: pivotal role of cellular senescence in vascular smooth muscle cells. Exp Gerontol 45:819–824. https://doi.org/10.1016/j.exger.2010.07.005
Case AJ (2017) On the origin of superoxide dismutase: an evolutionary perspective of superoxide-mediated redox signaling. Antioxidants (Basel) 6:82. https://doi.org/10.3390/antiox6040082
Cattan V, Mercier N, Gardner JP et al (2008) Chronic oxidative stress induces a tissue-specific reduction in telomere length in CAST/Ei mice. Free Radic Biol Med 44:1592–1598. https://doi.org/10.1016/J.FREERADBIOMED.2008.01.007
Chandrasekaran A, del Pilar Sosa Idelchik M, Melendez JA (2016) Redox control of senescence and age-related disease. Redox Biol 11:91–102. https://doi.org/10.1016/j.redox.2016.11.005
Cheeseman KH, Slater TF (1993) An introduction to free radical biochemistry. Br Med Bull 49:481–493. https://doi.org/10.1093/OXFORDJOURNALS.BMB.A072625
Chen Y, Zheng Y, Liu L et al (2017) Adiponectin inhibits TNF-α-activated PAI-1 expression via the cAMP-PKA-AMPK-NF-κB axis in human umbilical vein endothelial cells. Cell Physiol Biochem 42:2342–2352. https://doi.org/10.1159/000480006
Choe M, Titov DV (2022) Genetically encoded tools for measuring and manipulating metabolism. Nat Chem Biol 18:451–460. https://doi.org/10.1038/s41589-022-01012-8
Chu X, Raju RP (2022) Regulation of NAD+ metabolism in aging and disease. Metabolism 126:154923. https://doi.org/10.1016/j.metabol.2021.154923
Clark RA, Volpp BD, Leidal KG, Nauseef WM (1990) Two cytosolic components of the human neutrophil respiratory burst oxidase translocate to the plasma membrane during cell activation. J Clin Investig 85:714–721. https://doi.org/10.1172/JCI114496
Coppé JP, Patil CK, Rodier F et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. https://doi.org/10.1371/JOURNAL.PBIO.0060301
Coppé JP, Patil CK, Rodier F et al (2010) A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE. https://doi.org/10.1371/JOURNAL.PONE.0009188
Davalos AR, Coppe JP, Campisi J, Desprez PY (2010) Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev 29:273–283. https://doi.org/10.1007/S10555-010-9220-9
De Duve C, Baudhuin P (1966) Peroxisomes (microbodies and related particles). Physiol Rev 46:323–357. https://doi.org/10.1152/PHYSREV.1966.46.2.323
De la Fuente M, Miquel J (2009) An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des 15:3003–3026. https://doi.org/10.2174/138161209789058110
Di Micco R, Cicalese A, Fumagalli M et al (2008) DNA damage response activation in mouse embryonic fibroblasts undergoing replicative senescence and following spontaneous immortalization. Cell Cycle 7:3601–3606. https://doi.org/10.4161/CC.7.22.7152
Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147
Dodson M, Darley-Usmar V, Zhang J (2013) Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic Biol Med 63:207–221. https://doi.org/10.1016/j.freeradbiomed.2013.05.014
Eisenbarth SC, Colegio OR, O’Connor W et al (2008) Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 453:1122–1126. https://doi.org/10.1038/nature06939
El-Benna J, Hurtado-Nedelec M, Marzaioli V et al (2016) Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol Rev 273:180–193. https://doi.org/10.1111/imr.12447
Emanuele E, Minoretti P, Sanchis-Gomar F et al (2014) Can enhanced autophagy be associated with human longevity? Serum levels of the Autophagy biomarker beclin-1 are increased in healthy centenarians. Rejuvenation Res 17:518–524. https://doi.org/10.1089/rej.2014.1607
Ferrante G, Nakano M, Prati F et al (2010) High levels of systemic myeloperoxidase are associated with coronary plaque erosion in patients with acute coronary syndromes: a clinicopathological study. Circulation 122:2505–2513. https://doi.org/10.1161/CIRCULATIONAHA.110.955302
Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15. https://doi.org/10.1083/jcb.201102095
Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. https://doi.org/10.1038/35041687
Flachsbart F, Caliebe A, Kleindorp R et al (2009) Association of FOXO3A variation with human longevity confirmed in german centenarians. Proc Natl Acad Sci USA 106:2700–2705. https://doi.org/10.1073/pnas.0809594106
Freund A, Orjalo AV, Desprez PY, Campisi J (2010) Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16:238–246. https://doi.org/10.1016/J.MOLMED.2010.03.003
Fukai T, Ushio-Fukai M (2011) Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 15:1583–1606. https://doi.org/10.1089/ars.2011.3999
Gabig TG, Babior BM (1979) The O2(-)-forming oxidase responsible for the respiratory burst in human neutrophils. Properties of the solubilized enzyme. J Biol Chem 254:9070–9074
Galimov ER (2010) The role of p66shc in oxidative stress and apoptosis. Acta Nat 2:44–51
Garg AK, Aggarwal BB (2002) Reactive oxygen intermediates in TNF signaling. Mol Immunol 39:509–517. https://doi.org/10.1016/S0161-5890(02)00207-9
Gladyshev VN (2014) The free radical theory of aging is dead. Long live the damage theory! Antioxid Redox Signal 20:727–731. https://doi.org/10.1089/ars.2013.5228
Grishkovskaya I, Paumann-Page M, Tscheliessnig R et al (2017) Structure of human promyeloperoxidase (proMPO) and the role of the propeptide in processing and maturation. J Biol Chem 292:8244–8261. https://doi.org/10.1074/jbc.M117.775031
Gross E, Sevier CS, Heldman N et al (2006) Generating disulfides enzymatically: reaction products and electron acceptors of the endoplasmic reticulum thiol oxidase Ero1p. Proc Natl Acad Sci USA 103:299–299. https://doi.org/10.1073/PNAS.0506448103
Gu Y, Han J, Jiang C, Zhang Y (2020) Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 59:101036. https://doi.org/10.1016/j.arr.2020.101036
Gui T, Burgering BMT (2022) FOXOs: masters of the equilibrium. FEBS J 289:7918–7939. https://doi.org/10.1111/febs.16221
Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150. https://doi.org/10.1042/BST0351147
Hamanaka RB, Chandel NS (2010) Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci 35:505–513. https://doi.org/10.1016/j.tibs.2010.04.002
Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:6274. https://doi.org/10.1038/345458a0
Heo S, Kim S, Kang D (2020) The role of hydrogen peroxide and peroxiredoxins throughout the cell cycle. Antioxidants (Basel) 9:280. https://doi.org/10.3390/antiox9040280
Hu Y, Luo Y, Zheng Y (2022) Nrf2 pathway and autophagy crosstalk: new insights into therapeutic strategies for ischemic cerebral vascular diseases. Antioxidants 11:1747. https://doi.org/10.3390/antiox11091747
Hubackova S, Krejcikova K, Bartek J, Hodny Z (2012) IL1- and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine “bystander senescence.” Aging 4:932–951. https://doi.org/10.18632/AGING.100520
Hussain F, Warraich U-E-A, Jamil A (2022) Redox signalling, autophagy and ageing. In: Çakatay U (ed) Redox signaling and biomarkers in ageing. Springer International Publishing, Cham, pp 117–145
Hütter E, Unterluggauer H, Überall F et al (2002) Replicative senescence of human fibroblasts: the role of ras-dependent signaling and oxidative stress. Exp Gerontol 37:1165–1174. https://doi.org/10.1016/S0531-5565(02)00136-5
Iakovou E, Kourti M (2022) A comprehensive overview of the complex role of oxidative stress in aging, the contributing environmental stressors and emerging antioxidant therapeutic interventions. Front Aging Neurosci 14:558. https://doi.org/10.3389/FNAGI.2022.827900/BIBTEX
Ichimura Y, Waguri S, Sou Y-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
Iskandar K, Rezlan M, Yadav SK et al (2016) Synthetic lethality of a novel small molecule against mutant KRAS-expressing cancer cells involves AKT-dependent ROS production. Antioxid Redox Signal 24:781–794. https://doi.org/10.1089/ARS.2015.6362
Izeradjene K, Douglas L, Tillman DM et al (2005) Reactive oxygen species regulate caspase activation in tumor necrosis factor-related apoptosis-inducing ligand-resistant human colon carcinoma cell lines. Cancer Res 65:7436–7445. https://doi.org/10.1158/0008-5472.CAN-04-2628
Jacobs LJHC, Riemer J (2023) Maintenance of small molecule redox homeostasis in mitochondria. FEBS Lett 597:205–223. https://doi.org/10.1002/1873-3468.14485
Jiang H, Schiffer E, Song Z et al (2008) Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci USA 105:11299–11304. https://doi.org/10.1073/PNAS.0801457105
Kadenbach B (2003) Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim Biophys Acta 1604:77–94. https://doi.org/10.1016/S0005-2728(03)00027-6
Kamiński M, Kießling M, Süss D et al (2007) Novel role for mitochondria: protein kinase Cθ-dependent oxidative signaling organelles in activation-induced T-cell death. Mol Cell Biol 27:3625–3639. https://doi.org/10.1128/MCB.02295-06
Kastl L, Sauer SW, Ruppert T et al (2014) TNF-α mediates mitochondrial uncoupling and enhances ROS-dependent cell migration via NF-κB activation in liver cells. FEBS Lett 588:175–183. https://doi.org/10.1016/j.febslet.2013.11.033
Kataura T, Otten EG, Rabanal-Ruiz Y et al (2022) NDP52 acts as a redox sensor in PINK1/Parkin‐mediated mitophagy. EMBO J 42:e111372. https://doi.org/10.15252/embj.2022111372
Khan A, Alsahli M, Rahmani A (2018) Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Med Sci 6:33. https://doi.org/10.3390/medsci6020033
Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120:437–447. https://doi.org/10.1016/J.CELL.2005.01.027
Kirkwood TBL, Austad SN (2000) Why do we age? Nature 408:233–238. https://doi.org/10.1038/35041682
Klebanoff SJ (1970) Myeloperoxidase: contribution to the microbicidal activity of intact leukocytes. Science 169:1095–1097. https://doi.org/10.1126/science.169.3950.1095
Klotz L-O, Sánchez-Ramos C, Prieto-Arroyo I et al (2015) Redox regulation of FoxO transcription factors. Redox Biol 6:51–72. https://doi.org/10.1016/j.redox.2015.06.019
Kodama R, Kato M, Furuta S et al (2013) ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic ras-induced premature senescence. Genes Cells 18:32–41. https://doi.org/10.1111/GTC.12015
Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292:18–36. https://doi.org/10.1152/AJPREGU.00327.2006
Krishnamurthy J, Ramsey MR, Ligon KL et al (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453–457. https://doi.org/10.1038/NATURE05092
Kudryashova KS, Burka K, Kulaga AY et al (2020) Aging biomarkers: from functional tests to multi-omics approaches. Proteomics 20:1900408. https://doi.org/10.1002/pmic.201900408
Laberge R-M, Awad P, Campisi J, Desprez P-Y (2011) Epithelial–mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron 5:39–44. https://doi.org/10.1007/s12307-011-0069-4
Lagnado A, Leslie J, Ruchaud-Sparagano M et al (2021) Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner. EMBO J. https://doi.org/10.15252/EMBJ.2020106048
Lambeth JD, Neish AS (2014) Nox enzymes and new thinking on reactive oxygen: a double-edged sword revisited. Annu Rev Pathol Mech Dis 9:119–145. https://doi.org/10.1146/annurev-pathol-012513-104651
Lapierre LR, De Magalhaes Filho CD, McQuary PR et al (2013) The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun 4:2267. https://doi.org/10.1038/ncomms3267
Laurindo FRM (2018) Redox cellular signaling pathways in endothelial dysfunction and vascular disease. In: Endothelium and cardiovascular diseases: vascular biology and clinical syndromes. pp 127–145. https://doi.org/10.1016/B978-0-12-812348-5.00010-6
Lee DH, Park JS, Lee YS et al (2020) SQSTM1/p62 activates NFE2L2/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity. Autophagy 16:1949–1973. https://doi.org/10.1080/15548627.2020.1712108
Lesina M, Wörmann SM, Morton J et al (2016) RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. J Clin Investig 126:2919–2932. https://doi.org/10.1172/JCI86477
Leto TL, Geiszt M (2006) Role of Nox family NADPH oxidases in host defense. Antioxid Redox Signal 8:1549–1561. https://doi.org/10.1089/ars.2006.8.1549
Li D, Ding Z, Du K et al (2021) Reactive oxygen species as a link between antioxidant pathways and autophagy. Oxid Med Cell Longev 2021:5583215. https://doi.org/10.1155/2021/5583215
Liguori I, Russo G, Curcio F et al (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13:757. https://doi.org/10.2147/CIA.S158513
Longo VD, Mitteldorf J, Skulachev VP (2005) Programmed and altruistic ageing. Nat Rev Genet 6(11):866–872. https://doi.org/10.1038/nrg1706
Lopez-Castejon G, Brough D (2011) Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev 22:189–195. https://doi.org/10.1016/j.cytogfr.2011.10.001
López-Otín C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217. https://doi.org/10.1016/J.CELL.2013.05.039
Ludlow AT, Spangenburg EE, Chin ER et al (2014) Telomeres shorten in response to oxidative stress in mouse skeletal muscle fibers. J Gerontol Ser A Biol Sci Med Sci 69:821–830. https://doi.org/10.1093/GERONA/GLT211
Marichal T, Ohata K, Bedoret D et al (2011) DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med 17:996–1002. https://doi.org/10.1038/nm.2403
Marino N, Putignano G, Cappilli S et al (2023) Towards AI-driven longevity research: an overview. Front Aging 4:1057204. https://doi.org/10.3389/fragi.2023.1057204
Massudi H, Grant R, Braidy N et al (2012) Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS ONE. https://doi.org/10.1371/JOURNAL.PONE.0042357
Matheu A, Maraver A, Klatt P et al (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448:375–379. https://doi.org/10.1038/nature05949
McCarthy DA, Clark RR, Bartling TR et al (2013) Redox control of the senescence regulator interleukin-1α and the secretory phenotype. J Biol Chem 288:32149–32159. https://doi.org/10.1074/JBC.M113.493841
McKelvey TG, Höllwarth ME, Granger DN et al (1988) Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney. Am J Physiol 254:G753–760. https://doi.org/10.1152/ajpgi.1988.254.5.G753
McKenna E, Traganos F, Zhao H, Darzynkiewicz Z (2012) Persistent DNA damage caused by low levels of mitomycin C induces irreversible cell senescence. Cell Cycle (Georgetown Tex) 11:3132–3140. https://doi.org/10.4161/CC.21506
McReynolds MR, Chellappa K, Baur JA (2020) Age-related NAD+ decline. Exp Gerontol 134:110888. https://doi.org/10.1016/j.exger.2020.110888
Missiroli S, Genovese I, Perrone M et al (2020) The role of mitochondria in inflammation: from cancer to neurodegenerative disorders. J Clin Med 9:740. https://doi.org/10.3390/jcm9030740
Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861–2873. https://doi.org/10.1101/gad.1599207
Moskalev AA, Shaposhnikov MV, Plyusnina EN et al (2013) The role of DNA damage and repair in aging through the prism of Koch-like criteria. Ageing Res Rev 12:661–684. https://doi.org/10.1016/J.ARR.2012.02.001
Mostafa DK, Nayel OA, Abdulmalek S et al (2022) Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging. Inflammopharmacology 30:2521–2535. https://doi.org/10.1007/s10787-022-01041-8
Muzaffar S, Shukla N, Lobo C et al (2004) Iloprost inhibits superoxide formation and gp91phox expression induced by the thromboxane A2 analogue U46619, 8-isoprostane F2alpha, prostaglandin F2alpha, cytokines and endotoxin in the pig pulmonary artery. Br J Pharmacol 141:488–496. https://doi.org/10.1038/sj.bjp.0705626
Mylonas C, Kouretas D (1999) Lipid peroxidation and tissue damage. In Vivo (Athens Greece) 13:295–309
Nacarelli T, Lau L, Fukumoto T et al (2019) NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol 21:397–407. https://doi.org/10.1038/s41556-019-0287-4
Nakahata N (2008) Thromboxane A2: physiology/pathophysiology, cellular signal transduction and pharmacology. Pharmacol Ther 118:18–35. https://doi.org/10.1016/j.pharmthera.2008.01.001
Nathan C, Cunningham-Bussel A (2013) Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat Rev Immunol 13:349–361. https://doi.org/10.1038/nri3423
Nauseef WM, McCormick SJ, Goedken M (1998) Coordinated participation of calreticulin and calnexin in the biosynthesis of myeloperoxidase. J Biol Chem 273:7107–7111. https://doi.org/10.1074/jbc.273.12.7107
Nelson G, Wordsworth J, Wang C et al (2012) A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11:345–349. https://doi.org/10.1111/J.1474-9726.2012.00795.X
Nelson G, Kucheryavenko O, Wordsworth J, von Zglinicki T (2018) The senescent bystander effect is caused by ROS-activated NF-κB signalling. Mech Ageing Dev 170:30–36. https://doi.org/10.1016/j.mad.2017.08.005
Nguyen GT, Green ER, Mecsas J (2017) Neutrophils to the ROScue: mechanisms of NADPH oxidase activation and bacterial resistance. Front Cell Infect Microbiol 7:373. https://doi.org/10.3389/fcimb.2017.00373
Novakova Z, Hubackova S, Kosar M et al (2010) Cytokine expression and signaling in drug-induced cellular senescence. Oncogene 29:273–284. https://doi.org/10.1038/ONC.2009.318
Ogrunc M, Di Micco R, Liontos M et al (2014) Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation. Cell Death Differ 21(6):998–1012. https://doi.org/10.1038/cdd.2014.16
Orjalo AV, Bhaumik D, Gengler BK et al (2009) Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci USA 106:17031–17036. https://doi.org/10.1073/PNAS.0905299106
Pacher P, Nivorozhkin A, Szabó C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114. https://doi.org/10.1124/pr.58.1.6
Pal S, Tyler JK (2016) Epigenetics and aging. Sci Adv. https://doi.org/10.1126/SCIADV.1600584
Parvez S, Long MJC, Poganik JR, Aye Y (2018) Redox signaling by reactive electrophiles and oxidants. Chem Rev 118:8798–8888. https://doi.org/10.1021/acs.chemrev.7b00698
Passos JF, Nelson G, Wang C et al (2010) Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. https://doi.org/10.1038/MSB.2010.5
Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4:89–89
Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30:11–11. https://doi.org/10.1007/S12291-014-0446-0
Pineda-Pampliega J, Herrera-Dueñas A, Mulder E et al (2020) Antioxidant supplementation slows telomere shortening in free-living white stork chicks. Proc Biol Sci. https://doi.org/10.1098/RSPB.2019.1917
Pyo J-O, Yoo S-M, Ahn H-H et al (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300. https://doi.org/10.1038/ncomms3300
Rahman MA, Ahmed KR, Haque F et al (2023) Recent advances in cellular signaling interplay between redox metabolism and autophagy modulation in cancer: an overview of molecular mechanisms and therapeutic interventions. Antioxidants (Basel) 12:428. https://doi.org/10.3390/antiox12020428
Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990. https://doi.org/10.1016/J.CELLSIG.2012.01.008
Rehring JF, Bui TM, Galán-Enríquez CS et al (2021) Released myeloperoxidase attenuates neutrophil migration and accumulation in inflamed tissue. Front Immunol 12:654259. https://doi.org/10.3389/fimmu.2021.654259
Salminen A, Ojala J, Kaarniranta K et al (2011) Astrocytes in the aging brain express characteristics of senescence-associated secretory phenotype. Eur J Neurosci 34:3–11. https://doi.org/10.1111/J.1460-9568.2011.07738.X
Santos AL, Sinha S, Lindner AB (2018) The Good, the bad, and the ugly of ROS: new insights on aging and aging-related diseases from eukaryotic and prokaryotic model organisms. Oxid Med Cell Longev 2018:1941285. https://doi.org/10.1155/2018/1941285
Saretzki G, Von Zglinicki T (2002) Replicative aging, telomeres, and oxidative stress. Ann N Y Acad Sci 959:24–29. https://doi.org/10.1111/J.1749-6632.2002.TB02079.X
Scherz-Shouval R, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 17:422–427. https://doi.org/10.1016/j.tcb.2007.07.009
Schrader M, Fahimi HD (2006) Peroxisomes and oxidative stress. Biochim Biophys Acta 1763:1755–1766. https://doi.org/10.1016/J.BBAMCR.2006.09.006
Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832. https://doi.org/10.1016/j.cell.2010.01.040
Si Y, Shi H, Lee K (2009) Metabolic flux analysis of mitochondrial uncoupling in 3T3-L1 adipocytes. PLoS ONE 4:e7000. https://doi.org/10.1371/journal.pone.0007000
Slater TW, Finkielsztein A, Mascarenhas LA et al (2017) Neutrophil microparticles deliver active myeloperoxidase to injured mucosa to inhibit epithelial wound healing. J Immunol 198:2886–2897. https://doi.org/10.4049/jimmunol.1601810
Smith KA, Waypa GB, Schumacker PT (2017) Redox signaling during hypoxia in mammalian cells. Redox Biol 13:228–234. https://doi.org/10.1016/j.redox.2017.05.020
Song S, Lam EWF, Tchkonia T et al (2020) Senescent cells: emerging targets for human aging and age-related diseases. Trends Biochem Sci 45:578–592. https://doi.org/10.1016/J.TIBS.2020.03.008
Starkov AA (2008) The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 1147:37–52. https://doi.org/10.1196/ANNALS.1427.015
Stead ER, Castillo-Quan JI, Miguel VEM et al (2019) Agephagy—adapting autophagy for health during aging. Front Cell Dev Biol 7:308. https://doi.org/10.3389/fcell.2019.00308
Su Y, Xu C, Sun Z et al (2019) S100A13 promotes senescence-associated secretory phenotype and cellular senescence via modulation of non-classical secretion of IL-1α. Aging 11:549–572. https://doi.org/10.18632/AGING.101760
Syslová K, Böhmová A, Mikoška M et al (2014) Multimarker screening of oxidative stress in aging. Oxid Med Cell Longev. https://doi.org/10.1155/2014/562860
Von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–344. https://doi.org/10.1016/S0968-0004(02)02110-2
Wajapeyee N, Serra RW, Zhu X et al (2008) Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell 132:363–374. https://doi.org/10.1016/J.CELL.2007.12.032
Waters DW, Schuliga M, Pathinayake PS et al (2021) A senescence bystander effect in human lung fibroblasts. Biomedicines. https://doi.org/10.3390/BIOMEDICINES9091162
Wei Y, Jia S, Ding Y et al (2023) Balanced basal-levels of ROS (redox-biology), and very-low-levels of pro-inflammatory cytokines (cold-inflammaging), as signaling molecules can prevent or slow-down overt-inflammaging, and the aging-associated decline of adaptive-homeostasis. Exp Gerontol 172:112067. https://doi.org/10.1016/j.exger.2022.112067
Winterbourn CC (2020) Hydrogen peroxide reactivity and specificity in thiol-based cell signalling. Biochem Soc Trans 48:745–754. https://doi.org/10.1042/BST20190049
Winterbourn CC, Hampton MB, Livesey JH, Kettle AJ (2006) Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome. J Biol Chem 281:39860–39869. https://doi.org/10.1074/jbc.M605898200
Wood SH, van Dam S, Craig T et al (2015) Transcriptome analysis in calorie-restricted rats implicates epigenetic and post-translational mechanisms in neuroprotection and aging. Genome Biol. https://doi.org/10.1186/S13059-015-0847-2
Yanar K, Atayik MC, Simsek B, Çakatay U (2020) Novel biomarkers for the evaluation of aging-induced proteinopathies. Biogerontology 21:531–548. https://doi.org/10.1007/s10522-020-09878-8
Yun J, Finkel T (2014) Mitohormesis. Cell Metab 19:757–766. https://doi.org/10.1016/J.CMET.2014.01.011
Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965. https://doi.org/10.1038/nm.1851
Zhang B, Pan C, Feng C et al (2022) Role of mitochondrial reactive oxygen species in homeostasis regulation. Redox Rep 27:45–52. https://doi.org/10.1080/13510002.2022.2046423
Zhou J, Li X-Y, Liu Y-J et al (2022) Full-coverage regulations of autophagy by ROS: from induction to maturation. Autophagy 18:1240–1255. https://doi.org/10.1080/15548627.2021.1984656
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Javali, P.S., Sekar, M., Kumar, A. et al. Dynamics of redox signaling in aging via autophagy, inflammation, and senescence. Biogerontology 24, 663–678 (2023). https://doi.org/10.1007/s10522-023-10040-3
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DOI: https://doi.org/10.1007/s10522-023-10040-3