dc.creator | Aragonès, Gemma | es |
dc.creator | Dasuri, Kalavathi | es |
dc.creator | Olukorede, Opeoluwa | es |
dc.creator | Francisco, Sarah G. | es |
dc.creator | Renneburg, Carol | es |
dc.creator | Kumsta, Caroline | es |
dc.creator | Daza Navarro, María Paula | es |
dc.creator | Ruano Caballero, Diego | es |
dc.creator | Domínguez Martín, Helena | es |
dc.creator | Taylor, Allen | es |
dc.date.accessioned | 2021-04-16T15:23:37Z | |
dc.date.available | 2021-04-16T15:23:37Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Aragonès, G., Dasuri, K., Olukorede, O., Francisco, S.G., Renneburg, C., Kumsta, C.,...,Taylor, A. (2020). Autophagic receptor p62 protects against glycation-derived toxicity and enhances viability. Aging Cell, 19 (11), e13257. | |
dc.identifier.issn | 1474-9718 | es |
dc.identifier.issn | 1474-9726 | es |
dc.identifier.uri | https://hdl.handle.net/11441/107253 | |
dc.description.abstract | Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age-related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62-dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age-related diseases, including age-related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62-dependent autophagy offers novel potential therapeutic targets to treat AGEs-related pathologies. | es |
dc.description.sponsorship | National Institutes of Health R01AG028664, R21AG058038, R01EY021212, R01EY026979, R01EY028559 | es |
dc.description.sponsorship | U.S. Department of Agriculture 8050-51000-089-01S | es |
dc.description.sponsorship | Human Nutrition Research Center on Aging 2016–08885 | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad SAF 2016 78666‐R | es |
dc.format | application/pdf | es |
dc.format.extent | 17 p. | es |
dc.language.iso | eng | es |
dc.publisher | Wiley-Blackwell | es |
dc.relation.ispartof | Aging Cell, 19 (11), e13257. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Aging | es |
dc.subject | Autophagy | es |
dc.subject | Glycative stress | es |
dc.subject | p62 | es |
dc.subject | Proteotoxicity | es |
dc.title | Autophagic receptor p62 protects against glycation-derived toxicity and enhances viability | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Biología Celular | es |
dc.relation.projectID | R01AG028664 | es |
dc.relation.projectID | R21AG058038 | es |
dc.relation.projectID | R01EY021212 | es |
dc.relation.projectID | R01EY026979 | es |
dc.relation.projectID | R01EY028559 | es |
dc.relation.projectID | 8050-51000-089-01S | es |
dc.relation.projectID | 2016–08885 | es |
dc.relation.projectID | SAF 2016 78666‐R | es |
dc.relation.publisherversion | http://dx.doi.org/10.1111/acel.13257 | es |
dc.identifier.doi | 10.1111/acel.13257 | es |
dc.journaltitle | Aging Cell | es |
dc.publication.volumen | 19 | es |
dc.publication.issue | 11 | es |
dc.publication.initialPage | e13257 | es |