Oxidative stress and cellular senescence are involved in the aging kidney
Entidad
UAM. Departamento de MedicinaEditor
MDPIFecha de edición
2022-01-31Cita
10.3390/antiox11020301
Antioxidants 11.2 (2022): 301
ISSN
2076-3921 (online)DOI
10.3390/antiox11020301Financiado por
This research was funded by grants from the Instituto de Salud Carlos III (ISCIII); Fondos FEDER European Union (PI17/00119, PI20/00140; and DTS20/00083 to M.R.-O.; PI18/01133 to A.M.R.); Sara Borrell’ program from Instituto de Salud Carlos III (ISCIII) (grant number CD20/00042 to R.R.R.-D.); Red de Investigación Renal REDINREN: RD16/0009/0003 and RICORS program to RICORS2040 496 (RD21/0005), to M.R.-O., Sociedad Española de Nefrología; “NOVELREN-CM: Enfermedad renal crónica: nuevas Estrategias para la prevención, Diagnóstico y tratamiento” (B2017/BMD3751 to M.R.-O.); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); Juan de la Cierva incorporacion grant: IJC2018-035187-I to S.R.-M.; innovation program under the Marie Skłodowska-Curie grant of the European Union’s Horizon 2020 (IMProvePD ID: 812699) to M.R.-O.; and Fundacion Conchita Rabago to L.T.-SProyecto
Gobierno de España. PI17/00119; Gobierno de España. PI18/01133; Comunidad de Madrid. B2017/BMD3751; Gobierno de España. EIN2019-103294; info:eu-repo/grantAgreement/EC/H2020/812699/EU//MSCVersión del editor
https://doi.org/10.3390/antiox11020301Materias
Aging kidney; Cellular senescence; Fibrosis; Inflammaging; NRF2; Oxidation; MedicinaDerechos
© 2022 by the authorsResumen
Chronic kidney disease (CKD) can be considered as a clinical model for premature aging. However, non‐invasive biomarkers to detect early kidney damage and the onset of a senescent phenotype are lacking. Most of the preclinical senescence studies in aging have been done in very old mice. Furthermore, the precise characterization and over-time development of age-related senes-cence in the kidney remain unclear. To address these limitations, the age-related activation of cellular senescence-associated mechanisms and their correlation with early structural changes in the kidney were investigated in 3- to 18-month-old C57BL6 mice. Inflammatory cell infiltration was ob-served by 12 months, whereas tubular damage and collagen accumulation occurred later. Early activation of cellular-senescence-associated mechanisms was found in 12-month-old mice, character-ized by activation of the DNA-damage-response (DDR), mainly in tubular cells; activation of the antioxidant NRF2 pathway; and klotho downregulation. However, induction of tubular-cell-cycle-arrest (CCA) and overexpression of renal senescent-associated secretory phenotype (SASP) components was only found in 18-month-old mice. In aging mice, both inflammation and oxidative stress (marked by elevated lipid peroxidation and NRF2 inactivation) remained increased. These findings support the hypothesis that prolonged DDR and CCA, loss of nephroprotective factors (klotho), and dysfunctional redox regulatory mechanisms (NRF2/antioxidant defense) can be early drivers of age-related kidney-damage progression
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Artículo principal
Google Scholar:Márquez-Expósito, Laura
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Tejedor Santamaria, Lucía
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Valentijn, Floris A.
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Tejera-Muñoz, Antonio
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Rayego-Mateos, Sandra
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Marchant, Vanessa
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Rodrigues-Diez, Raul R.
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Rubio-Soto, Irene
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Knoppert, Sebastiaan N.
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Ortiz Arduán, Alberto
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Ramos, Adrián M.
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Goldschmeding, Roel
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Ruiz Ortega, Marta
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