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Sexual dimorphic responses of C57BL/6 mice to Fisetin or Dasatinib and Quercetin cocktail oral treatment

View ORCID ProfileYimin Fang, David Medina, Robert Stockwell, Sam McFadden, Kathleen Quinn, Mackenzie R. Peck, View ORCID ProfileAndrzej Bartke, View ORCID ProfileKevin N. Hascup, View ORCID ProfileErin R. Hascup
doi: https://doi.org/10.1101/2021.11.08.467509
Yimin Fang
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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David Medina
2Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Robert Stockwell
2Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Sam McFadden
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Kathleen Quinn
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Mackenzie R. Peck
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Andrzej Bartke
2Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
3Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Kevin N. Hascup
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
3Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
4Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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Erin R. Hascup
1Department of Neurology, Dale and Deborah Smith Center for Alzheimer’s Research and Treatment, Neuroscience Institute, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
4Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
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  • For correspondence: ehascup@siumed.edu
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Abstract

Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. We hypothesized that administering senotherapeutics in young adulthood of mice would slow physiological markers of aging through mid-life. C57BL/6 mice were treated monthly with either Fisetin or a Dasatinib (D) plus Quercetin (Q) cocktail from 4-13 months of age. Fisetin treated male mice had reduced senescence-associated secretory phenotype (SASP), enhanced glucose and energy metabolism, improved cognitive performance, and increased hippocampal expression of adiponectin 1 receptor and glucose transporter 4. D+Q treated females had increased SASP expression along with accumulation of white adipose tissue, reduced energy metabolism, and cognitive performance. Senotherapeutics in young adulthood, has beneficial, negligible, or detrimental effects in mice dependent upon sex and treatment.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 08, 2021.
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Sexual dimorphic responses of C57BL/6 mice to Fisetin or Dasatinib and Quercetin cocktail oral treatment
Yimin Fang, David Medina, Robert Stockwell, Sam McFadden, Kathleen Quinn, Mackenzie R. Peck, Andrzej Bartke, Kevin N. Hascup, Erin R. Hascup
bioRxiv 2021.11.08.467509; doi: https://doi.org/10.1101/2021.11.08.467509
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Sexual dimorphic responses of C57BL/6 mice to Fisetin or Dasatinib and Quercetin cocktail oral treatment
Yimin Fang, David Medina, Robert Stockwell, Sam McFadden, Kathleen Quinn, Mackenzie R. Peck, Andrzej Bartke, Kevin N. Hascup, Erin R. Hascup
bioRxiv 2021.11.08.467509; doi: https://doi.org/10.1101/2021.11.08.467509

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