scholarly journals Effect of Combined Dasatinib and Fisetin Treatment on Senescent Cell Clearance in Monkeys

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 131-132
Author(s):  
Ricki Colman ◽  
Tamara Tchkonia ◽  
Tamar Pirtskhalava ◽  
Nino Giorgadze ◽  
Larissa Prata ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Preliminary Evidence ◽  
Senescent Cell ◽  
Myelogenous Leukemia ◽  
Primate Model ◽  
Age Related ◽  
Cell Clearance ◽  
Female Rhesus

Abstract Aging is the biggest risk factor for the most serious chronic diseases and disabilities. Cellular senescence, a state in which cells stop dividing but release factors that damage other cells, may contribute to both age-related and chronic diseases. Removal of senescent cells from aged mice has been shown to delay aging and age–related disabilities. Our goal was to determine the ability of potential senolytic agents to remove senescent cells in a primate model. Several agents and combinations were tested including Fisetin, Navitoclax, combined Dasatinib and Quercetin, and combined Dasatinib and Fisetin. Here we describe the Dasatinib and Fisetin trial. Dasatinib is an FDA approved oral anticancer drug that has been used to treat chronic myelogenous leukemia in humans. Fisetin is a flavonoid that can be found in many plants, particularly strawberries, and acts as a coloring agent. After baseline measurements, six older (mean age=21 years) female rhesus monkeys (Macaca mulatta) were given a combined oral dose of Dasatinib (5 mg/kg) and Fisetin (100 mg/kg) on two consecutive days. Animals were additionally assessed at 1- and 7-weeks following dosing. At 7 weeks post dosing, there were fewer (p<0.05) p16+ cells in the epidermis compared to baseline. Similarly, there was a reduction (p<0.05) in p21+ cells in the epidermis at 1- and 7-weeks post dosing compared to baseline. There were no negative outcomes associated with treatment. This study provides preliminary evidence for the senolytic potential of combined Dasatinib and Fisetin treatment and indicates that pharmacological mitigation of age-related changes is possible.

A nonhuman primate model of age-related bone loss: a longitudinal study in male and premenopausal female rhesus monkeys

Bone ◽  
2001 ◽  
Vol 28 (3) ◽  
pp. 295-302 ◽  
Author(s):  
A Black ◽  
E.M Tilmont ◽  
A.M Handy ◽  
W.W Scott ◽  
S.A Shapses ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Bone Loss ◽  
Nonhuman Primate ◽  
Rhesus Monkeys ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Age Related ◽  
Female Rhesus ◽  
Premenopausal Female

Immunization with Dextransucrases, Levansucrases, and Glycosidic Hydrolases from Oral Streptococci. II. Immunization with Glucosyltransferases, Fructosyltransferases, and Glycosidic Hydrolases from Oral Streptococci in Monkeys

1977 ◽  
Vol 56 (12) ◽  
pp. 1586-1598 ◽  
Author(s):  
Arthur N. Bahn ◽  
Irving L. Shklair ◽  
James A. Hayashi
Keyword(s):  
Dental Caries ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Control Group ◽  
Oral Streptococci ◽  
Primate Model ◽  
Pathological Effect ◽  
Carious Lesions ◽  
Gross Lesions

The feasibility of immunizing monkeys with enzymes from oral streptococci in an attempt to reduce dental caries was investigated. Forty rhesus monkeys, Macaca mulatta, were used. Cariogenic streptococci, S mutans, were implanted into all the monkeys' mouths. There was no pathological effect resulting from immunization. Of the 40 animals, 30 retained the implanted flora throughout the experiment; the remaining 10 were reimplanted until the streptococci remained. In six months, gross carious lesions were evident with plaque. Inhibitors present in the monkey sera after immunization inhibited glucosyltransferase, fructosyltransferase, and neuraminidase activzties. It was presumed the inhibitors were antibodies. There was a reduction of 68.6% in the total carious lesions in the animals immunized intraorally with glucosyltransferase, 62.4% reduction in those injected with fructosyltransferase, and 57.4% reduction in total lesions in those immunized with glycosidic hydro lases after 19 months, as compared to the control group. There were no gross lesions apparent in the group immunized with glycosidic hydrolases. It appears that immunization with enzymes significantly reduces caries and is feasible in a primate model.

Age-related changes in the vitreus and lens of rhesus monkeys (Macaca mulatta)

1980 ◽  
Vol 31 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Janet L. Denlinger ◽  
Georg Eisner ◽  
Endre A. Balazs
Keyword(s):  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Age Related ◽  
Age Related Changes

scholarly journals A New Gene Set Identifies Senescent Cells and Predicts Senescence-Associated Pathways Across Tissues

2021 ◽  
Author(s):  
Sundeep Khosla ◽  
Dominik Saul ◽  
Robyn Laura Kosinsky ◽  
Elizabeth Atkinson ◽  
Madison Doolittle ◽  
...  
Keyword(s):  
Single Cell ◽  
Mesenchymal Cells ◽  
Senescent Cell ◽  
Single Cell Level ◽  
Cell Level ◽  
Gene Set ◽  
Age Related ◽  
Cell Clearance ◽  
Bone Biopsies

Abstract Although cellular senescence is increasingly recognized as driving multiple age-related co-morbidities through the senescence-associated secretory phenotype (SASP), in vivo senescent cell identification, particularly in bulk or single cell RNA-sequencing (scRNA-seq) data remains challenging. Here, we generated a novel gene set (SenMayo) and first validated its enrichment in bone biopsies from two aged human cohorts. SenMayo also identified senescent cells in aged murine brain tissue, demonstrating applicability across tissues and species. For direct validation, we demonstrated significant reductions in SenMayo in bone following genetic clearance of senescent cells in mice, with similar findings in adipose tissue from humans in a pilot study of pharmacological senescent cell clearance. In direct comparisons, SenMayo outperformed all six existing senescence/SASP gene sets in identifying senescent cells across tissues and in demonstrating responses to senescent cell clearance. We next used SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from publicly available human and murine bone marrow/bone scRNA-seq data and identified monocytic and osteolineage cells, respectively, as showing the highest levels of senescence/SASP genes. Using pseudotime and cellular communication patterns, we found senescent hematopoietic and mesenchymal cells communicated with other cells through common pathways, including the Macrophage Migration Inhibitory Factor (MIF) pathway, which has been implicated not only in inflammation but also in immune evasion, an important property of senescent cells. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Moreover, using this senescence panel, we were able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways associated with these cells, which may be particularly useful for evolving efforts to map senescent cells (e.g., SenNet). In addition, SenMayo represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs.

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