Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease
Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9387 |
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| author | Felipe Salech Carol D. SanMartín Jorge Concha-Cerda Esteban Romero-Hernández Daniela P. Ponce Gianella Liabeuf Nicole K. Rogers Paola Murgas Bárbara Bruna Jamileth More María I. Behrens |
| author_facet | Felipe Salech Carol D. SanMartín Jorge Concha-Cerda Esteban Romero-Hernández Daniela P. Ponce Gianella Liabeuf Nicole K. Rogers Paola Murgas Bárbara Bruna Jamileth More María I. Behrens |
| author_sort | Felipe Salech |
| collection | DOAJ |
| description | Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients. |
| first_indexed | 2024-03-09T13:15:34Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:15:34Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7fbe7e0435054b6a87698317d27d61c52023-11-30T21:36:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316938710.3390/ijms23169387Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s DiseaseFelipe Salech0Carol D. SanMartín1Jorge Concha-Cerda2Esteban Romero-Hernández3Daniela P. Ponce4Gianella Liabeuf5Nicole K. Rogers6Paola Murgas7Bárbara Bruna8Jamileth More9María I. Behrens10Centro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChilePrograma de Fisiología y Biofísica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Obesidad y Metabolismo Energético (OMEGA), Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago 7830490, ChileDepartamento de Neurociencia, Facultad de Medicina de la Universidad de Chile, Santiago 8380453, ChileInstituto de Bioquímica y Microbiología, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5110566, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileCentro de Investigación Clínica Avanzada (CICA), Facultad de Medicina-Hospital Clínico, Universidad de Chile, Santiago 8380453, ChileRecent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.https://www.mdpi.com/1422-0067/23/16/9387cellular senescenceperipheral blood mononuclear cellsAlzheimer’s DiseaseaMCIaging |
| spellingShingle | Felipe Salech Carol D. SanMartín Jorge Concha-Cerda Esteban Romero-Hernández Daniela P. Ponce Gianella Liabeuf Nicole K. Rogers Paola Murgas Bárbara Bruna Jamileth More María I. Behrens Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease International Journal of Molecular Sciences cellular senescence peripheral blood mononuclear cells Alzheimer’s Disease aMCI aging |
| title | Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease |
| title_full | Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease |
| title_fullStr | Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease |
| title_full_unstemmed | Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease |
| title_short | Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease |
| title_sort | senescence markers in peripheral blood mononuclear cells in amnestic mild cognitive impairment and alzheimer s disease |
| topic | cellular senescence peripheral blood mononuclear cells Alzheimer’s Disease aMCI aging |
| url | https://www.mdpi.com/1422-0067/23/16/9387 |
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