On the biochemical associations of FoxO3a and SirT1 with the stress resistance of cells from the slow senescing Snell dwarf Mouse
- Published
- Accepted
- Subject Areas
- Biochemistry, Cell Biology, Neuroscience, Geriatrics
- Keywords
- aging/ senescence, FoxO3a, Snell Dwarf Mouse, neurogerontology, stress resistance, SirT1, longevity, attenuated aging/ slowed senescence, dwarf mice, gerontology
- Copyright
- © 2019 Arum
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 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.27791v1
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.
Author Comment
This is a preprint submission to PeerJ Preprints.
