Regulation of the p19(Arf)/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice

Aging Cell
Raúl Soriano-CantónIsabel Fariñas

Abstract

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1-NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age-related changes in B1-NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence-accelerated-prone mice (SAMP8) relative to senescence-accelerated-resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the study of aging. We have found that the B1-NSC compartment is transiently expanded in young SAMP8 relative to SAMR1 mice, resulting in disturbed cytoarchitecture of the SEZ, B1-NSC hyperproliferation, and higher yields of primary neurospheres. These unusual features are, however, accompanied by premature loss of B1-NSCs. Moreover, SAMP8 neurospheres lack self-renewal and enter p53-dependent senescence after only two passages. Interestingly, in vitro senescence of SAMP8 cells could be prevented by inhibition of histone acetyltransferases and mimick...Continue Reading

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Citations

Aug 25, 2016·BioMed Research International·Elizabeth E HullKathryn J Leyva
Sep 10, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Li-Qin ChengDe-Pei Liu
May 11, 2018·Stem Cells International·Hang ZhouYongxiang Wang
Aug 28, 2020·Frontiers in Aging Neuroscience·Alexandra M NicaiseStefano Pluchino
May 8, 2021·Frontiers in Neuroscience·Sara Rojas-VázquezIsabel Fariñas
Jul 30, 2020·Cell Stem Cell·Paloma Navarro NegredoAnne Brunet

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Methods Mentioned

BETA
confocal microscopy
scanning electron microscopy
acetylation
Protein assay
electrophoresis
PCR

Software Mentioned

GraphPad Prism
InCell investigator
imagej

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