Senescence in primary rat astrocytes induces loss of the mitochondrial membrane potential and alters mitochondrial dynamics in cortical neurons.
Open accessAbstract
The decline in brain function during aging is one of the most critical health problems nowadays. Although senescent astrocytes have been found in old-age brains and neurodegenerative diseases, their impact on the function of other cerebral cell types is unknown. The aim of this study was to evaluate the effect of senescent astrocytes on the mitochondrial function of a neuron. In order to evaluate neuronal susceptibility to a long and constant senescence-associated secretory phenotype (SASP) exposure, we developed a model by using cellular cocultures in transwell plates. Rat primary cortical astrocytes were seeded in transwell inserts and induced to premature senescence with hydrogen peroxide [stress-induced premature senescence (SIPS)]. Independently, primary rat cortical neurons were seeded at the bottom of transwells. After neuronal 6 days in vitro (DIV), the inserts with SIPS-astrocytes were placed in the chamber and cocultured with neurons for 6 more days. The neuronal viability, the redox state [reduced glutathione/oxidized glutathione (GSH/GSSG)], the mitochondrial morphology, and the proteins and membrane potential were determined. Our results showed that the neuronal mitochondria functionality was altered after being cocultured with senescent astrocytes. In vivo, we found that old animals had diminished mitochondrial oxidative phosphorylation (OXPHOS) proteins, redox state, and senescence markers as compared to young rats, suggesting effects of the senescent astrocytes similar to the ones we observed in vitro. Overall, these results indicate that the microenvironment generated by senescent astrocytes can affect neuronal mitochondria and physiology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Primary senescent astrocytes from rats induce loss of mitochondrial membrane potential and alter mitochondrial dynamics in cortical neurons.
“In addition to this finding, primary senescent astrocytes from rats induce loss of mitochondrial membrane potential and alter mitochondrial dynamics in cortical neurons (Morales-Rosales et al., 2021).”
From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Morales-Rosales et al., 2021
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1× · see citing works
“On the other hand, benefits of the clearance of senescent cells have been reported (Baker et al., 2011; Hernandez-Segura et al., 2018; TrianaMartínez et al., 2019).”
BackgroundFour faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · cited 1× · see citing works
“In addition, senescent cells, through the senescence-associated secretory phenotype (SASP), secrete a complex mixture of factors, including proinflammatory cytokines and tissue remodelers, that may adversely affect neighboring cells and tissues with chronic inflammatory signals and oxidative stress (Rodier and Campisi…”
BackgroundAstrocyte Senescence as a Component of Alzheimer’s Disease
Bhat, R., Crowe, E. P., Bitto, A., Moh, M., Katsetos, C. D., Garcia, F. U., Johnson, F. B., Trojanowski, J. Q., Sell, C., & Torres, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045069 · Cited by 586 · see citing works
Self-citationChinta, S. J., Woods, G., Demaria, M., Rane, A., Zou, Y., McQuade, A., Rajagopalan, S., Limbad, C., Madden, D. T., Campisi, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.092 · Cited by 530 · see citing works
Identification and characterization of Cardiac Glycosides as senolytic compounds
Triana-Martínez, F., Picallos-Rabina, P., Da Silva-Álvarez, S., Pietrocola, F., Llanos, S., Rodilla, V., Soprano, E., Pedrosa, P., Ferreirós, A., Barradas, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12888-x · Cited by 384 · see citing works
Astrocyte senescence: Evidence and significance
Cohen, J., & Torres, C. (2019) · Aging Cell · doi:10.1111/acel.12937 · Cited by 281 · see citing works
Self-citationAstrocyte senescence promotes glutamate toxicity in cortical neurons
Limbad, C., Oron, T. R., Alimirah, F., Davalos, A. R., Tracy, T. E., Gan, L., Desprez, P.-Y., & Campisi, J. (2020) · PLOS ONE · doi:10.1371/journal.pone.0227887 · Cited by 183 · see citing works
Perrott, K. M., Wiley, C. D., Desprez, P.-Y., & Campisi, J. (2017) · GeroScience · doi:10.1007/s11357-017-9970-1 · Cited by 163 · see citing works
Flagged first, then by citations
Research works printed but not linked: 44
- Adaniya S. M. O-Uchi J. Cypress M. W. Kusakari Y. Jhun B. S. (2019). Posttranslational modifications of mitochondrial fission and fusion proteins in cardiac physiology and pathophysiology. Am. J. Physiol. Cell Physiol. 316 C583– C604. 30758993 PMC6580160
- Antelo-Iglesias L. Picallos-Rabina P. Estévez-Souto V. Da Silva-Álvarez S. Collado M. (2021). The role of cellular senescence in tissue repair and regeneration. Mech. Ageing Dev. 198: 111528. 10.1016/j.mad.2021.111528 34181964 · DOI
- Baulies A. Montero J. Matías N. Insausti N. Terrones O. Basañez G. (2018). The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading. Redox Biol. 14 164– 177. 10.1016/j.redox.2017.08.022 28942194 PMC5609874 · DOI
- Bouzier-Sore A.-K. Pellerin L. (2013). Unraveling the complex metabolic nature of astrocytes. Front. Cell. Neurosci. 7: 179. 10.3389/fncel.2013.00179 24130515 PMC3795301 · DOI · Paper page
- Boveris A. Navarro A. (2008). Brain mitochondrial dysfunction in aging. IUBMB Life 60 308– 314. 10.1002/iub.46 18421773 · DOI · Paper page
- Brewer G. J. Torricelli J. R. Evege E. K. Price P. J. (1993). Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. J. Neurosci. Res. 35 567– 576. 10.1002/jnr.490350513 8377226 · DOI · Paper page
- Chakrabarti S. Munshi S. Banerjee K. Thakurta I. G. Sinha M. Bagh M. B. (2011). Mitochondrial dysfunction during brain aging: role of oxidative stress and modulation by antioxidant supplementation. Aging Dis. 2 242– 256. 22396876 PMC3295058
- Chinta S. J. Woods G. Rane A. Demaria M. Campisi J. Andersen J. K. (2015). Cellular senescence and the aging brain. Exp. Gerontol. 68 3– 7. 10.18632/aging.100871 25281806 PMC4382436 · DOI · Paper page
- Cid-Castro C. Hernández-Espinosa D. R. Morán J. (2018). ROS as regulators of mitochondrial dynamics in neurons. Cell. Mol. Neurobiol. 38 995– 1007. 10.1007/s10571-018-0584-7 29687234 PMC11481975 · DOI
- Cohen J. D’Agostino L. Tuzer F. Torres C. (2018). HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs. Mech. Ageing Dev. 175 74– 82. 10.1016/j.mad.2018.07.008 30055190 PMC6133242 · DOI
- Cohen J. D’Agostino L. Wilson J. Tuzer F. Torres C. (2017). Astrocyte senescence and metabolic changes in response to HIV antiretroviral therapy drugs. Front. Aging Neurosci. 9: 281. 10.3389/fnagi.2017.00281 28900395 PMC5581874 · DOI · Paper page
- Dienel G. A. (2017). The metabolic trinity, glucose-glycogen-lactate, links astrocytes and neurons in brain energetics, signaling, memory, and gene expression. Neurosci. Lett. 637 18– 25. 10.1016/j.neulet.2015.02.052 25725168 · DOI
- Dimri G. P. Lee X. Basile G. Acosta M. Scott G. Roskelley C. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl. Acad. Sci. U.S.A. 92 9363– 9367. 10.1073/pnas.92.20.9363 7568133 PMC40985 · DOI · Paper page
- Dringen R. Gutterer J. M. Hirrlinger J. (2000). Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur. J. Biochem. 267 4912– 4916. 10.1046/j.1432-1327.2000.01597.x 10931173 · DOI
- Franceschi C. Capri M. Monti D. Giunta S. Olivieri F. Sevini F. (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128 92– 105. 10.1016/j.mad.2006.11.016 17116321 · DOI · Paper page
- Gerónimo-Olvera C. Montiel T. Rincon-Heredia R. Castro-Obregón S. Massieu L. (2017). Autophagy fails to prevent glucose deprivation/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons. Cell Death Dis. 8: e2911. 10.1038/cddis.2017.299 28661473 PMC5520945 · DOI
- Guerrero A. De Strooper B. Arancibia-Cárcamo I. L. (2021). Cellular senescence at the crossroads of inflammation and Alzheimer’s disease. Trends Neurosci. 44 714– 727. 10.1016/j.tins.2021.06.007 34366147 · DOI · Paper page
- Hernandez-Segura A. Nehme J. Demaria M. (2018). Hallmarks of cellular senescence. Trends Cell Biol. 28 436– 453. 10.1016/j.tcb.2018.02.001 29477613 · DOI · Paper page
- Jha M. K. Morrison B. M. (2018). Glia-neuron energy metabolism in health and diseases: new insights into the role of nervous system metabolic transporters. Exp. Neurol. 309 23– 31. 10.1016/j.expneurol.2018.07.009 30044944 PMC6156776 · DOI · Paper page
- Jiang T. Cadenas E. (2014). Astrocytic metabolic and inflammatory changes as a function of age. Aging Cell 13 1059– 1067. 10.1111/acel.12268 25233945 PMC4244278 · DOI
- Kirchhoff F. Dringen R. Giaume C. (2001). Pathways of neuron-astrocyte interactions and their possible role in neuroprotection. Eur. Arch. Psychiatry Clin. Neurosci. 251 159– 169. 10.1007/s004060170036 11697580 · DOI
- LaFrance R. Brustovetsky N. Sherburne C. Delong D. Dubinsky J. M. (2005). Age-related changes in regional brain mitochondria from Fischer 344 rats. Aging Cell 4 139– 145. 10.1111/j.1474-9726.2005.00156.x 15924570 · DOI
- López-Otín C. Blasco M. A. Partridge L. Serrano M. Kroemer G. (2013). The hallmarks of aging. Cell 153 1194– 1217. 23746838 PMC3836174
- Maciel-Barón L. Á Moreno-Blas D. Morales-Rosales S. L. González-Puertos V. Y. López-Díazguerrero N. E. Torres C. (2018b). Cellular senescence, neurological function, and redox state. Antioxid. Redox Signal. 28 1704– 1723. 10.1089/ars.2017.7112 28467755 · DOI
- Maciel-Barón L. Á Morales-Rosales S. L. Silva-Palacios A. Rodríguez-Barrera R. H. García-Álvarez J. A. Luna-López A. (2018a). The secretory phenotype of senescent astrocytes isolated from Wistar newborn rats changes with anti-inflammatory drugs, but does not have a short-term effect on neuronal mitochondrial potential. Biogerontology 19 415– 433. 10.1007/s10522-018-9767-3 30097900 · DOI
- Matias I. Morgado J. Gomes F. C. A. (2019). Astrocyte heterogeneity: impact to brain aging and disease. Front. Aging Neurosci. 11: 59. 10.3389/fnagi.2019.00059 30941031 PMC6433753 · DOI · Paper page
- Mattson M. P. Arumugam T. V. (2018). Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab. 27 1176– 1199. 10.1016/j.cmet.2018.05.011 29874566 PMC6039826 · DOI · Paper page
- Mattson M. P. Gleichmann M. Cheng A. (2008). Mitochondria in neuroplasticity and neurological disorders. Neuron 60 748– 766. 10.1016/j.neuron.2008.10.010 19081372 PMC2692277 · DOI · Paper page
- McCarthy K. D. de Vellis J. (1980). Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85 890– 902. 10.1083/jcb.85.3.890 6248568 PMC2111442 · DOI
- Merrill R. A. Flippo K. H. Strack S. (2017). “ Measuring mitochondrial shape with imageJ,” in Techniques to Investigate Mitochondrial Function in Neurons, eds Strack S. Usachev Y. M. (New York, NY: Springer New York), 31– 48. 10.1007/978-1-4939-6890-9_2 · DOI
- Missiroli S. Genovese I. Perrone M. Vezzani B. Vitto V. A. M. Giorgi C. (2020). The role of mitochondria in inflammation: from cancer to neurodegenerative disorders. J. Clin. Med. Res. 9: 740. 10.3390/jcm9030740 32182899 PMC7141240 · DOI
- Nakamura T. Cieplak P. Cho D.-H. Godzik A. Lipton S. A. (2010). S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration. Mitochondrion 10 573– 578. 10.1016/j.mito.2010.04.007 20447471 PMC2918703 · DOI
- Pannese E. (2021). Quantitative, structural and molecular changes in neuroglia of aging mammals: a review. Eur. J. Histochem. 65: 3249. 10.4081/ejh.2021.3249 34346664 PMC8239453 · DOI
- Posadas-Rodríguez P. Posadas-Rodríguez N. E. González-Puertos V. Y. Toledo-Pérez R. Ventura-Gallegos J. L. Zentella A. (2020). tBHQ induces a hormetic response that protects L6 myoblasts against the toxic effect of palmitate. Oxid. Med. Cell. Longev. 2020: 3123268. 10.1155/2020/3123268 32509140 PMC7246405 · DOI
- Ricci G. Volpi L. Pasquali L. Petrozzi L. Siciliano G. (2009). Astrocyte-neuron interactions in neurological disorders. J. Biol. Phys. 35 317– 336. 10.1007/s10867-009-9157-9 19669420 PMC2750745 · DOI
- Ritschka B. Storer M. Mas A. Heinzmann F. Ortells M. C. Morton J. P. (2017). The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev. 31 172– 183. 10.1101/gad.290635.116 28143833 PMC5322731 · DOI · Paper page
- Rivero-Segura N. A. Coronado-Mares M. I. Rincón-Heredia R. Pérez-Torres I. Montiel T. Pavón N. (2019). Prolactin prevents mitochondrial dysfunction induced by glutamate excitotoxicity in hippocampal neurons. Neurosci. Lett. 701 58– 64. 10.1016/j.neulet.2019.02.027 30790645 · DOI
- Takahashi S. (2021). Neuroprotective function of high glycolytic activity in astrocytes: common roles in stroke and neurodegenerative diseases. Int. J. Mol. Sci. 22: 6568. 10.3390/ijms22126568 34207355 PMC8234992 · DOI
- Theurey P. Pizzo P. (2018). The aging mitochondria. Genes 9: 22. 10.3390/genes9010022 29315229 PMC5793175 · DOI
- Turnquist C. Horikawa I. Foran E. Major E. O. Vojtesek B. Lane D. P. (2016). p53 isoforms regulate astrocyte-mediated neuroprotection and neurodegeneration. Cell Death Differ. 23 1515– 1528. 10.1038/cdd.2016.37 27104929 PMC5072428 · DOI
- Van Eldik L. J. Carrillo M. C. Cole P. E. Feuerbach D. Greenberg B. D. Hendrix J. A. (2016). The roles of inflammation and immune mechanisms in Alzheimer’s disease. Alzheimers. Dement. 2 99– 109. 10.1016/j.trci.2016.05.001 29067297 PMC5644267 · DOI
- Vicente-Gutiérrez C. Jiménez-Blasco D. Quintana-Cabrera R. (2021). Intertwined ROS and metabolic signaling at the neuron-astrocyte interface. Neurochem. Res. 46 23– 33. 10.1007/s11064-020-02965-9 31989468 · DOI
- Wiley C. D. Campisi J. (2016). From Ancient pathways to aging cells-connecting metabolism and cellular senescence. Cell Metab. 23 1013– 1021. 10.1016/j.cmet.2016.05.010 27304503 PMC4911819 · DOI · Paper page
- Yan J. Fu Q. Cheng L. Zhai M. Wu W. Huang L. (2014). Inflammatory response in Parkinson’s disease (Review). Mol. Med. Rep. 10 2223– 2233. 25215472
Cited by
Sorted by citations
Aging promotes an increase in mitochondrial fragmentation in astrocytes
Araujo, A. P. B., Vargas, G., Hayashide, L. D. S., Matias, I., Andrade, C. B. V., de Carvalho, J. J., Gomes, F. C. A., & Diniz, L. P. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1496163 · Cited by 43 · see citing works
- Authors
- Morales-Rosales, S. L., Santín-Márquez, R., Posadas-Rodriguez, P., Rincon-Heredia, R., Montiel, T., Librado-Osorio, R., Luna-López, A., Rivero-Segura, N. A., Torres, C., Cano-Martínez, A., Silva-Palacios, A., Cortés-Hernández, P., Morán, J., Massieu, L., & Konigsberg, M.
- Affiliations
- Universidad Autónoma Metropolitana (MX)
- Universidad Nacional Autónoma de México (MX)
- Drexel University (US)
- Mexican Social Security Institute (MX)
- ORCID
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2021-12-01
- Volume
- 13
- Pages
- 766306-766306
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC8672143
- OpenAlex
- W3217592219
- Cited by
- 17
- References
- 8
- Citations by year
- 2026: 4 · 2024: 7 · 2023: 2 · 2022: 4
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- Consejo Nacional de Ciencia y Tecnología
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- astrocyte senescence, senescence-associated secretory phenotype, stress-induced premature senescence, hydrogen peroxide, cortical neurons, mitochondrial membrane potential, mitochondrial dynamics, mitochondrial oxidative phosphorylation, glutathione redox state, astrocyte-neuron co-culture, brain aging, neurodegeneration, cellular senescence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
