On the biochemical associations of FoxO3a and SirT1 with the stress resistance of cells from the slow senescing Snell dwarf Mouse
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Abstract
Tailskin fibroblasts from multiple genotypes of slow aging mice have been shown to be resistant to a broad spectrum of toxicants. The molecular determinants for this in vitro effect, as well as for the delayed/ decelerated senescence of these mice, are uncertain. Here, we have extended this phenomenon of in vitro cellular stress resistance to neurons derived from the cerebral cortex of the Snell Dwarf Mouse. We further investigated the role of the transcription factor FoxO3a and the protein deacetylase SirT1, proteins known to positively mediate cellular stress-resistance, in this paradigm. We found that Snell Dwarfs have a greater proportion of nuclear-localized FoxO3a within their cerebrums than their littermate controls and that the same is true for their unstressed fibroblasts in vitro; yet, Snell Dwarf fibroblasts did not differ in FoxO3a properties in response to the application of three different concentrations of two disparate stresses. Similar results were obtained for SirT1, although SirT1 content did increase under the mild cellular stress of serum deprivation. Taken together, these results depict stress resistance in non-fibroblast cell types of incontrovertible physiological import explanted from slow aging mice. Also, these results strongly suggest that neither FoxO3a nor SirT1 robustly regulate the stress-resistance of Snell Dwarf Mouse cells in vitro, and thus might not play a role in other slow aging mammalian in vitro models in which stress resistance has been documented. That cerebral neurons ex vivo and unstressed fibroblasts in vitro display FoxO3a concentrations suggestive of increased activity introduce the possibility that FoxO3a might partially mediate the in vivo retardation of senescence of these mice.
Cite this as
2019. On the biochemical associations of FoxO3a and SirT1 with the stress resistance of cells from the slow senescing Snell dwarf Mouse. PeerJ Preprints 7:e27791v1 https://doi.org/10.7287/peerj.preprints.27791v1Author comment
This is a preprint submission to PeerJ Preprints.
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Supplemental Information
Quantifications of immunoblotting band intensities, and statistical analyses & data presentations on such values
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Immunodetection of FoxO3a, SirT1, & P53 on Randomly selected Full Membranes
Additional Information
Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Oge Arum conceived and designed the experiments, performed the experiments, analyzed the data, prepared figures and/or tables, authored or reviewed drafts of the paper.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
The Institutional Animal Care & Use Committee (IACUC), supported by the Animal Care & Use Office (ACUO), of the University of Michigan - Ann Arbor.
Data Deposition
The following information was supplied regarding data availability:
Quantifications of immunoblotting band intensities, and statistical analyses & data presentations on such values (in .xls document) AND Immunodetections of FoxO3a, SirT1, & P53 on randomly selected full membranes (in 19 .jpg documents).
Funding
This study was funded by a National Institute on Aging (N.I.A.) T32 National Research Service Award (T32-AG000114) and N.I.A. grants AG024824 & AG023122). With regards to "study design", the grant applications compulsorily described the manner of cellular and biochemical analyses that were ultimately conducted within the study.
