{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:01:15Z","timestamp":1792468875684,"version":"4.5.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Sirtuin 6 (SIRT6) is a member of the mammalian sirtuin family of NAD\n                    <jats:sup>+<\/jats:sup>\n                    -dependent protein deacylases, homologues of the yeast silent information regulator 2 (Sir2). SIRT6 has remarkably diverse functions and plays a key role in a variety of biological processes for maintaining cellular and organismal homeostasis. In this review, our primary aim is to summarize recent progress in understanding SIRT6\u2019s functions in the retina and retinal pigment epithelium (RPE), with the hope of further drawing interests in SIRT6 to increase efforts in exploring the therapeutic potential of this unique protein in the vision field. Before describing SIRT6\u2019s role in the eye, we first discuss SIRT6\u2019s general functions in a wide range of biological contexts. SIRT6 plays an important role in gene silencing, metabolism, DNA repair, antioxidant defense, inflammation, aging and longevity, early development, and stress response. In addition, recent studies have revealed SIRT6\u2019s role in macrophage polarization and mitochondrial homeostasis. Despite being initially understudied in the context of the eye, recent efforts have begun to elucidate the critical functions of SIRT6 in the retina and RPE. In the retina, SIRT6 is essential for adult retinal function, regulates energy metabolism by suppressing glycolysis that affects photoreceptor cell survival, protects retinal ganglion cells from oxidative stress, and plays a role in M\u00fcller cells during early neurodegenerative events in diabetic retinopathy. In the RPE, SIRT6 activates autophagy in culture and protects against oxidative stress in mice. Taken together, this review demonstrates that better understanding of SIRT6\u2019s functions and their mechanisms, both in and out of the context of the eye, holds great promise for the development of SIRT6-targeted strategies for prevention and treatment of blinding eye diseases.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2023.1244765","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T07:41:58Z","timestamp":1698824518000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["The many faces of SIRT6 in the retina and retinal pigment epithelium"],"prefix":"10.3389","volume":"11","author":[{"given":"Jie","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey J.","family":"Keuthan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Esumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1101\/gad.1588507","article-title":"Motif module map reveals enforcement of aging by continual NF-kappaB activity","volume":"21","author":"Adler","year":"2007","journal-title":"Genes Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1016\/j.exger.2013.04.010","article-title":"Light-dark condition regulates sirtuin mRNA levels in the retina","volume":"48","author":"Ban","year":"2013","journal-title":"Exp. Gerontol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrm.2017.7","article-title":"Biomolecular condensates: organizers of cellular biochemistry","volume":"18","author":"Banani","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41586-022-04618-z","article-title":"Somatic mutation rates scale with lifespan across mammals","volume":"604","author":"Cagan","year":"2022","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1152\/physrev.00030.2018","article-title":"SIRT6, a mammalian deacylase with multitasking abilities","volume":"100","author":"Chang","year":"2020","journal-title":"Physiol. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9677","DOI":"10.1080\/21655979.2022.2059610","article-title":"The role of Sirt6 in osteoarthritis and its effect on macrophage polarization","volume":"13","author":"Chen","year":"","journal-title":"Bioengineered"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e13296","DOI":"10.1111\/cpr.13296","article-title":"Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1-Drp1 signalling pathway","volume":"55","author":"Chen","year":"","journal-title":"Cell Prolif."},{"key":"B9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s12017-022-08715-0","article-title":"Overexpressing SIRT6 can attenuate the injury of intracerebral hemorrhage by down-regulating NF-kB","volume":"25","author":"Cheng","year":"2023","journal-title":"Neuromolecular Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5067","DOI":"10.1167\/iovs.07-1422","article-title":"Functional rescue of degenerating photoreceptors in mice homozygous for a hypomorphic cGMP phosphodiesterase 6 b allele (Pde6bH620Q)","volume":"49","author":"Davis","year":"2008","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"16891","DOI":"10.1074\/jbc.M500166200","article-title":"Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants","volume":"280","author":"Dhakshinamoorthy","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/ncb3147","article-title":"The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine","volume":"17","author":"Etchegaray","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1016\/j.bbrc.2018.01.159","article-title":"Autophagy activated by SIRT6 regulates A\u03b2 induced inflammatory response in RPEs","volume":"496","author":"Feng","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1101\/gad.307330.117","article-title":"An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality","volume":"32","author":"Ferrer","year":"2018","journal-title":"Genes Dev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"9732","DOI":"10.1021\/acs.jmedchem.1c00601","article-title":"Emerging therapeutic potential of SIRT6 modulators","volume":"64","author":"Fiorentino","year":"2021","journal-title":"J. Med. Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1007\/s11357-022-00713-1","article-title":"Human centenarian-associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids","volume":"45","author":"Frohlich","year":"2023","journal-title":"Geroscience"},{"key":"B17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.biochi.2023.03.002","article-title":"Molecular integrative study on interaction domains of nuclear factor erythroid 2-related factor 2 with sirtuin 6","volume":"211","author":"Fu","year":"2023","journal-title":"Biochimie"},{"key":"B18","doi-asserted-by":"publisher","first-page":"9181","DOI":"10.1093\/nar\/gkaa661","article-title":"The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2","volume":"48","author":"Geng","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1167\/iovs.04-0860","article-title":"Expression of acute-phase response proteins in retinal Muller cells in diabetes","volume":"46","author":"Gerhardinger","year":"2005","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1016\/j.celrep.2015.10.006","article-title":"Lamin A is an endogenous SIRT6 activator and promotes SIRT6-mediated DNA repair","volume":"13","author":"Ghosh","year":"2015","journal-title":"Cell Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.freeradbiomed.2015.06.017","article-title":"Regulation of catalase expression in healthy and cancerous cells","volume":"87","author":"Glorieux","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2537","DOI":"10.1038\/cddis.2016.453","article-title":"Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration","volume":"8","author":"Golestaneh","year":"2017","journal-title":"Cell Death Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.cell.2016.05.061","article-title":"Dangerous entrapment for NRF2","volume":"165","author":"Gorbunova","year":"2016","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s13238-010-0113-z","article-title":"Human catalase: looking for complete identity","volume":"1","author":"Goyal","year":"2010","journal-title":"Protein Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e39847","DOI":"10.1371\/journal.pone.0039847","article-title":"Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NF\u03baB responses","volume":"7","author":"Grimley","year":"2012","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.cell.2020.03.049","article-title":"RNA-induced conformational switching and clustering of G3BP drive stress granule assembly by condensation","volume":"181","author":"Guillen-Boixet","year":"2020","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1101\/gad.1467506","article-title":"Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction","volume":"20","author":"Haigis","year":"2006","journal-title":"Genes Dev."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7084","DOI":"10.1096\/fj.201802752R","article-title":"Enhanced SIRT6 activity abrogates the neurotoxic phenotype of astrocytes expressing ALS-linked mutant SOD1","volume":"33","author":"Harlan","year":"2019","journal-title":"FASEB J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1167\/iovs.05-0254","article-title":"Genotype-phenotype correlation of mouse pde6b mutations","volume":"46","author":"Hart","year":"2005","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"32804","DOI":"10.1074\/jbc.M404800200","article-title":"Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury","volume":"279","author":"Ho","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.preteyeres.2014.06.003","article-title":"Functional architecture of the retina: development and disease","volume":"42","author":"Hoon","year":"2014","journal-title":"Prog. Retin Eye Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1093\/nar\/gkaa006","article-title":"SIRT6 coordinates with CHD4 to promote chromatin relaxation and DNA repair","volume":"48","author":"Hou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/s41589-018-0150-0","article-title":"Identification of a cellularly active SIRT6 allosteric activator","volume":"14","author":"Huang","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1146\/annurev-vision-100419-115156","article-title":"Retina metabolism and metabolism in the pigmented epithelium: a busy intersection","volume":"7","author":"Hurley","year":"2021","journal-title":"Annu. Rev. Vis. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"5166","DOI":"10.1242\/jcs.130708","article-title":"The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals","volume":"126","author":"Jedrusik-Bode","year":"2013","journal-title":"J. Cell Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1619651","DOI":"10.1155\/2022\/1619651","article-title":"MDL-800, the SIRT6 activator, suppresses inflammation via the NF-\u03baB pathway and promotes angiogenesis to accelerate cutaneous wound healing in mice","volume":"2022","author":"Jiang","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"837544","DOI":"10.3389\/fphar.2022.837544","article-title":"SIRT6 activator UBCS039 inhibits thioacetamide-induced hepatic injury in vitro and in vivo","volume":"13","author":"Jiao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3999","DOI":"10.1096\/fj.201700098RR","article-title":"Hepatocyte-specific sirtuin 6 deletion predisposes to nonalcoholic steatohepatitis by up-regulation of Bach1, an Nrf2 repressor","volume":"31","author":"Ka","year":"2017","journal-title":"FASEB J."},{"key":"B40","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1080\/15548627.2022.2069437","article-title":"Autophagy in age-related macular degeneration","volume":"19","author":"Kaarniranta","year":"2023","journal-title":"Autophagy"},{"key":"B41","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/nature10815","article-title":"The sirtuin SIRT6 regulates lifespan in male mice","volume":"483","author":"Kanfi","year":"2012","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"718548","DOI":"10.3389\/fimmu.2021.718548","article-title":"Research progress on the structure and function of G3BP","volume":"12","author":"Kang","year":"2021","journal-title":"Front. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e28899","DOI":"10.7554\/eLife.28899","article-title":"Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye","volume":"6","author":"Kanow","year":"2017","journal-title":"Elife"},{"key":"B44","doi-asserted-by":"publisher","first-page":"10872","DOI":"10.1096\/fj.201900767R","article-title":"The nuclear and mitochondrial sirtuins, Sirt6 and Sirt3, regulate each other's activity and protect the heart from developing obesity-mediated diabetic cardiomyopathy","volume":"33","author":"Kanwal","year":"2019","journal-title":"FASEB J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.cell.2008.10.052","article-title":"SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span","volume":"136","author":"Kawahara","year":"2009","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e1002153","DOI":"10.1371\/journal.pgen.1002153","article-title":"Dynamic chromatin localization of sirt6 shapes stress- and aging-related transcriptional networks","volume":"7","author":"Kawahara","year":"2011","journal-title":"PLoS Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.jhep.2019.06.019","article-title":"The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice","volume":"71","author":"Kim","year":"2019","journal-title":"J. Hepatol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"11021","DOI":"10.1074\/jbc.REV120.011438","article-title":"Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators","volume":"295","author":"Klein","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e108863","DOI":"10.15252\/embj.2021108863","article-title":"Autophagy in major human diseases","volume":"40","author":"Klionsky","year":"2021","journal-title":"EMBO J."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0248-9","article-title":"Myeloid cell-specific sirtuin 6 deficiency delays wound healing in mice by modulating inflammation and macrophage phenotypes","volume":"51","author":"Koo","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.tcb.2021.06.009","article-title":"Sirtuin 6: linking longevity with genome and epigenome stability","volume":"31","author":"Korotkov","year":"2021","journal-title":"Trends Cell Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1016\/j.cell.2016.05.017","article-title":"Repression of the antioxidant NRF2 pathway in premature aging","volume":"165","author":"Kubben","year":"2016","journal-title":"Cell"},{"key":"B53","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.cmet.2019.03.003","article-title":"Watch what you (self-) eat: autophagic mechanisms that modulate metabolism","volume":"29","author":"Lahiri","year":"2019","journal-title":"Cell Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"100846","DOI":"10.1016\/j.preteyeres.2020.100846","article-title":"The cell biology of the retinal pigment epithelium","volume":"78","author":"Lakkaraju","year":"2020","journal-title":"Prog. Retin Eye Res."},{"key":"B55","doi-asserted-by":"publisher","first-page":"762","DOI":"10.3390\/ijms20030762","article-title":"Is retinal metabolic dysfunction at the center of the pathogenesis of age-related macular degeneration?","volume":"20","author":"Leveillard","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e13104","DOI":"10.1111\/acel.13104","article-title":"A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice","volume":"19","author":"Li","year":"2020","journal-title":"Aging Cell"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1080\/09168451.2020.1788377","article-title":"Sirtuin 6 protects human retinal pigment epithelium cells from LPS-induced inflammation and apoptosis partly by regulating autophagy","volume":"84","author":"Liu","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s41467-017-00498-4","article-title":"Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling","volume":"8","author":"Liu","year":"2017","journal-title":"Nat. Commun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/s41440-021-00631-3","article-title":"Sirtuin 6 attenuates angiotensin II-induced vascular adventitial aging in rat aortae by suppressing the NF-\u03baB pathway","volume":"44","author":"Liu","year":"2021","journal-title":"Hypertens. Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"113409","DOI":"10.1016\/j.yexcr.2022.113409","article-title":"Sirt6 mediates antioxidative functions by increasing Nrf2 abundance","volume":"422","author":"Liu","year":"2023","journal-title":"Exp. Cell Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"9855","DOI":"10.1073\/pnas.0708405105","article-title":"How vision begins: an odyssey","volume":"105","author":"Luo","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B62","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1126\/science.1202723","article-title":"SIRT6 promotes DNA repair under stress by activating PARP1","volume":"332","author":"Mao","year":"2011","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e55828","DOI":"10.7554\/eLife.55828","article-title":"Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice","volume":"9","author":"Meng","year":"2020","journal-title":"Elife"},{"key":"B65","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/nature06736","article-title":"SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin","volume":"452","author":"Michishita","year":"2008","journal-title":"Nature"},{"key":"B66","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.4161\/cc.8.16.9367","article-title":"Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6","volume":"8","author":"Michishita","year":"2009","journal-title":"Cell Cycle"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4623","DOI":"10.1091\/mbc.e05-01-0033","article-title":"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins","volume":"16","author":"Michishita","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1074\/mcp.M113.032847","article-title":"A proteomic perspective of Sirtuin 6 (SIRT6) phosphorylation and interactions and their dependence on its catalytic activity","volume":"13","author":"Miteva","year":"2014","journal-title":"Mol. Cell Proteomics"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.4161\/auto.36184","article-title":"Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD","volume":"10","author":"Mitter","year":"2014","journal-title":"Autophagy"},{"key":"B70","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev."},{"key":"B71","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cell.2005.11.044","article-title":"Genomic instability and aging-like phenotype in the absence of mammalian SIRT6","volume":"124","author":"Mostoslavsky","year":"2006","journal-title":"Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/d41586-018-05970-9","article-title":"Role for the longevity protein SIRT6 in primate development","volume":"560","author":"Naiman","year":"2018","journal-title":"Nature"},{"key":"B73","doi-asserted-by":"publisher","first-page":"e51636","DOI":"10.7554\/eLife.51636","article-title":"SIRT6 is a DNA double-strand break sensor","volume":"9","author":"Onn","year":"2020","journal-title":"Elife"},{"key":"B74","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/cr.2016.4","article-title":"SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2","volume":"26","author":"Pan","year":"2016","journal-title":"Cell Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.tcb.2016.05.004","article-title":"Principles and properties of stress granules","volume":"26","author":"Protter","year":"2016","journal-title":"Trends Cell Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1089\/hum.2004.15.960","article-title":"Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress","volume":"15","author":"Rex","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"7914","DOI":"10.1093\/nar\/gkz528","article-title":"SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170","volume":"47","author":"Rezazadeh","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B78","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1038\/s41467-021-23545-7","article-title":"Restoration of energy homeostasis by SIRT6 extends healthy lifespan","volume":"12","author":"Roichman","year":"2021","journal-title":"Nat. Commun."},{"key":"B79","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.cell.2011.07.030","article-title":"Autophagy and aging","volume":"146","author":"Rubinsztein","year":"2011","journal-title":"Cell"},{"key":"B80","doi-asserted-by":"publisher","first-page":"769723","DOI":"10.3389\/fgene.2021.769723","article-title":"Metabolic imbalance effect on retinal muller glial cells reprogramming capacity: involvement of histone deacetylase SIRT6","volume":"12","author":"Sanhueza Salas","year":"2021","journal-title":"Front. Genet."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1126\/science.1106653","article-title":"Extension of murine life span by overexpression of catalase targeted to mitochondria","volume":"308","author":"Schriner","year":"2005","journal-title":"Science"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e98831","DOI":"10.1371\/journal.pone.0098831","article-title":"SIRT6 is required for normal retinal function","volume":"9","author":"Silberman","year":"2014","journal-title":"PLoS One"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.1038\/srep03085","article-title":"Proteomic analysis of the SIRT6 interactome: novel links to genome maintenance and cellular stress signaling","volume":"3","author":"Simeoni","year":"2013","journal-title":"Sci. Rep."},{"key":"B84","doi-asserted-by":"publisher","first-page":"e110393","DOI":"10.15252\/embj.2021110393","article-title":"A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A","volume":"41","author":"Simon","year":"2022","journal-title":"EMBO J."},{"key":"B85","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41419-022-05542-w","article-title":"SIRT6 is a key regulator of mitochondrial function in the brain","volume":"14","author":"Smirnov","year":"2023","journal-title":"Cell Death Dis."},{"key":"B86","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0256-9","article-title":"Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans","volume":"51","author":"Song","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"B87","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"B88","doi-asserted-by":"publisher","first-page":"6062","DOI":"10.1073\/pnas.0400782101","article-title":"A gene atlas of the mouse and human protein-encoding transcriptomes","volume":"101","author":"Su","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B89","doi-asserted-by":"publisher","first-page":"958","DOI":"10.4049\/jimmunol.1302341","article-title":"Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence","volume":"192","author":"Takasaka","year":"2014","journal-title":"J. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/nsmb.3202","article-title":"SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence","volume":"23","author":"Tasselli","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.cell.2019.03.043","article-title":"SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species","volume":"177","author":"Tian","year":"2019","journal-title":"Cell"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1089\/ars.2017.7342","article-title":"Transcriptional regulation by Nrf2","volume":"29","author":"Tonelli","year":"2018","journal-title":"Antioxid. Redox Signal"},{"key":"B93","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1083\/jcb.200212128","article-title":"The RasGAP-associated endoribonuclease G3BP assembles stress granules","volume":"160","author":"Tourriere","year":"2003","journal-title":"J. Cell Biol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"B95","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1172\/JCI79766","article-title":"Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice","volume":"125","author":"Venkatesh","year":"2015","journal-title":"J. Clin. Invest"},{"key":"B96","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. Retin Eye Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"656000","DOI":"10.3389\/fnmol.2021.656000","article-title":"A metabolic landscape for maintaining retina integrity and function","volume":"14","author":"Viegas","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"B98","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00395-016-0531-z","article-title":"SIRT6 protects cardiomyocytes against ischemia\/reperfusion injury by augmenting FoxO3\u03b1-dependent antioxidant defense mechanisms","volume":"111","author":"Wang","year":"2016","journal-title":"Basic Res. Cardiol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"714","DOI":"10.3390\/antiox12030714","article-title":"Caffeic acid phenethyl ester suppresses oxidative stress and regulates M1\/M2 microglia polarization via sirt6\/nrf2 pathway to mitigate cognitive impairment in aged mice following anesthesia and surgery","volume":"12","author":"Wang","year":"","journal-title":"Antioxidants (Basel)"},{"key":"B100","doi-asserted-by":"publisher","first-page":"110211","DOI":"10.1016\/j.intimp.2023.110211","article-title":"Ergothioneine inhibits the progression of osteoarthritis via the Sirt6\/NF-\u03baB axis both in vitro and in vivo","volume":"119","author":"Wang","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"e18413","DOI":"10.7554\/eLife.18413","article-title":"Distinct stages in stress granule assembly and disassembly","volume":"5","author":"Wheeler","year":"2016","journal-title":"Elife"},{"key":"B102","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","article-title":"Stress granules and neurodegeneration","volume":"20","author":"Wolozin","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"B103","doi-asserted-by":"publisher","first-page":"D313","DOI":"10.1093\/nar\/gkv1104","article-title":"BioGPS: building your own mash-up of gene annotations and expression profiles","volume":"44","author":"Wu","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"R130","DOI":"10.1186\/gb-2009-10-11-r130","article-title":"BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources","volume":"10","author":"Wu","year":"2009","journal-title":"Genome Biol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"17602","DOI":"10.1038\/srep17602","article-title":"Overexpression of Sirtuin 6 suppresses cellular senescence and NF-\u03baB mediated inflammatory responses in osteoarthritis development","volume":"5","author":"Wu","year":"2015","journal-title":"Sci. Rep."},{"key":"B106","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s00125-015-3778-2","article-title":"Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells","volume":"59","author":"Xiong","year":"2016","journal-title":"Diabetologia"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.3390\/cells9061513","article-title":"Protective effects of SIRT6 overexpression against DSS-induced colitis in mice","volume":"9","author":"Xu","year":"2020","journal-title":"Cells"},{"key":"B108","doi-asserted-by":"publisher","first-page":"e13760","DOI":"10.1111\/acel.13760","article-title":"Decreased Enterobacteriaceae translocation due to gut microbiota remodeling mediates the alleviation of premature aging by a high-fat diet","volume":"22","author":"Xu","year":"2023","journal-title":"Aging Cell"},{"key":"B109","doi-asserted-by":"publisher","first-page":"269","DOI":"10.4161\/15384101.2014.980641","article-title":"SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner","volume":"14","author":"Xu","year":"2015","journal-title":"Cell Cycle"},{"key":"B110","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.immuni.2014.01.006","article-title":"Transcriptome-based network analysis reveals a spectrum model of human macrophage activation","volume":"40","author":"Xue","year":"2014","journal-title":"Immunity"},{"key":"B111","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.cell.2020.03.046","article-title":"G3BP1 is a tunable switch that triggers phase separation to assemble stress granules","volume":"181","author":"Yang","year":"2020","journal-title":"Cell"},{"key":"B112","doi-asserted-by":"publisher","first-page":"e202201448","DOI":"10.26508\/lsa.202201448","article-title":"SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress","volume":"6","author":"Yang","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"B113","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3390\/antiox11010103","article-title":"Fine tuning of an oxidative stress model with sodium iodate revealed protective effect of NF-\u03baB inhibition and sex-specific difference in susceptibility of the retinal pigment epithelium","volume":"11","author":"Yang","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B114","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.cell.2009.09.029","article-title":"Phototransduction motifs and variations","volume":"139","author":"Yau","year":"2009","journal-title":"Cell"},{"key":"B115","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.cbi.2019.01.018","article-title":"SIRT6 protects retinal ganglion cells against hydrogen peroxide-induced apoptosis and oxidative stress by promoting Nrf2\/ARE signaling via inhibition of Bach1","volume":"300","author":"Yu","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"B116","doi-asserted-by":"publisher","first-page":"7302","DOI":"10.1039\/d2fo00966h","article-title":"Polydatin attenuates chronic alcohol consumption-induced cardiomyopathy through a SIRT6-dependent mechanism","volume":"13","author":"Yu","year":"2022","journal-title":"Food Funct."},{"key":"B117","doi-asserted-by":"publisher","first-page":"e1972","DOI":"10.1038\/cddis.2015.330","article-title":"Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration","volume":"6","author":"Zhang","year":"2015","journal-title":"Cell Death Dis."},{"key":"B118","doi-asserted-by":"publisher","first-page":"eabj3284","DOI":"10.1126\/sciadv.abj3284","article-title":"Maintenance of genome sequence integrity in long- and short-lived rodent species","volume":"7","author":"Zhang","year":"2021","journal-title":"Sci. Adv."},{"key":"B119","doi-asserted-by":"publisher","first-page":"4659","DOI":"10.1172\/JCI86905","article-title":"Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration","volume":"126","author":"Zhang","year":"2016","journal-title":"J. Clin. Invest"},{"key":"B120","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/s41586-018-0437-z","article-title":"SIRT6 deficiency results in developmental retardation in cynomolgus monkeys","volume":"560","author":"Zhang","year":"2018","journal-title":"Nature"},{"key":"B121","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1080\/15384101.2019.1568746","article-title":"Sirtuin 6 overexpression relieves sepsis-induced acute kidney injury by promoting autophagy","volume":"18","author":"Zhang","year":"2019","journal-title":"Cell Cycle"},{"key":"B122","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.cell.2009.12.041","article-title":"The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha","volume":"140","author":"Zhong","year":"2010","journal-title":"Cell"},{"key":"B123","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/jnc.14243","article-title":"Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6","volume":"144","author":"Zorrilla-Zubilete","year":"2018","journal-title":"J. Neurochem."},{"key":"B124","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13578-021-00725-y","article-title":"SIRT6 inhibition delays peripheral nerve recovery by suppressing migration, phagocytosis and M2-polarization of macrophages","volume":"11","author":"Zou","year":"2021","journal-title":"Cell Biosci."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1244765\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T07:42:07Z","timestamp":1698824527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1244765\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,1]]},"references-count":124,"alternative-id":["10.3389\/fcell.2023.1244765"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1244765","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,1]]},"article-number":"1244765"}}