Sexual dimorphic metabolic and cognitive responses of C57BL/6 mice to Fisetin or Dasatinib and quercetin cocktail oral treatment.
Sexual dimorphic metabolic and cognitive responses of C57BL/6 mice to Fisetin or Dasatinib and quercetin cocktail oral treatment.
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DOI：
10.1007/s11357-023-00843-0
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发表时间：
2023-10
期刊：
影响因子：
5.6
通讯作者：
Hascup, Erin R.
中科院分区：
文献类型：
--
作者：
Fang, Yimin;Medina, David;Stockwell, Robert;McFadden, Sam;Quinn, Kathleen;Peck, Mackenzie R.;Bartke, Andrzej;Hascup, Kevin N.;Hascup, Erin R.
老年小鼠的衰老治疗清除衰老的细胞负担，导致功能改善。然而，对于这些化合物在显著衰老细胞积累之前使用时的影响，人们知之甚少。从4-13个月龄的C57BL/6雄性和雌性小鼠，每月口服100 mg/kg非瑟丁或5 mg/kg达沙替尼(D)加50 mg/kg栎素(Q)鸡尾酒。在治疗期间，对健康衰老的几个方面进行了分析，包括使用胰岛素和葡萄糖耐量试验检测葡萄糖代谢，使用Morris水迷宫和新物体识别测试认知能力，以及使用间接量热法检测能量代谢。随后，对小鼠进行血浆、衰老相关分泌表型的组织特异性标志物(SASP)和白色脂肪组织积聚(WAT)的安乐死。观察性二形性治疗效果。Fisetin处理的雄性C57BL/6小鼠SASP减少，糖和能量代谢增强，认知功能改善，脂联素受体1和葡萄糖转运蛋白4mRNA表达增加。D + Q处理对雄性C57BL/6小鼠的影响很小，但对雌性C57BL/6小鼠不利，导致雌性小鼠SASP表达增加，WAT蓄积。能量代谢和认知能力的降低也被注意到了。非瑟素治疗对雌性C57BL/6小鼠没有影响，可能是由于生物衰老速度较慢。综上所述，青春期的衰老治疗对C57BL/6小鼠有有益的、可忽略的或有害的影响，依赖于性别和治疗。这些意见应在这一迅速发展和扩大的调查领域中起到警示作用。雄性和雌性C57BL/6小鼠从4-13个月龄开始，每月口服一次达沙替尼(D)、 + 、栎素(Q)或非瑟素。服用菲斯汀的男性SASP标志物(蓝色球体)减少，新陈代谢(红色火焰)和认知能力得到改善。接受D + Q治疗的女性肥胖程度和SASP标志物(红球)增加，新陈代谢(蓝色火焰)和认知能力下降。在服用非瑟丁的雌性或服用D + Q的雄性中没有观察到任何效果。在线版本包含补充材料，可在10.1007/s11357-023-023-0找到。
Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. However, less is known regarding the effects of these compounds when administered prior to significant senescent cell accumulation. From 4–13 months of age, C57BL/6 male and female mice received monthly oral dosing of either 100 mg/kg Fisetin or a 5 mg/kg Dasatinib (D) plus 50 mg/kg Quercetin (Q) cocktail. During treatment, several aspects of healthy aging were assayed including glucose metabolism using an insulin and glucose tolerance test, cognitive performance using Morris water maze and novel object recognition, and energy metabolism using indirect calorimetry. Afterwards, mice were euthanized for plasma, tissue specific markers of senescence-associated secretory phenotype (SASP), and white adipose tissue accumulation (WAT). Sexually dimorphic treatment effects were observed. Fisetin treated male mice had reduced SASP, enhanced glucose and energy metabolism, improved cognitive performance, and increased mRNA expression of adiponectin receptor 1 and glucose transporter 4. D + Q treatment had minimal effects in male C57BL/6 mice, but was detrimental to females causing increased SASP expression along with accumulation of WAT depots. Reduced energy metabolism and cognitive performance were also noted. Fisetin treatment had no effect in female C57BL/6 mice potentially due to a slower rate of biological aging. In summary, the senolytic treatment in young adulthood, has beneficial, negligible, or detrimental effects in C57BL/6 mice dependent upon sex and treatment. These observations should serve as a note of caution in this rapidly evolving and expanding field of investigation. Male and female C57BL/6 mice were treated with once monthly oral doses of either Dasatinib (D) + Quercetin (Q) or Fisetin from 4–13 months of age. Males treated with Fisetin had reduced SASP markers (blue spheres) as well as improved metabolism (red flame) and cognition. Females treated with D + Q had increased adiposity and SASP markers (red spheres) along with decreased metabolism (blue flame) and cognitive performance. No effects were observed in females treated with Fisetin or males treated with D + Q. The online version contains supplementary material available at 10.1007/s11357-023-00843-0.
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影响因子：
3.4
作者：
Khatoon S;Agarwal NB;Samim M;Alam O
通讯作者：
Alam O
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
5.2
作者：
Baumann, Cory W.;Kwak, Dongmin;Thompson, LaDora, V
通讯作者：
Thompson, LaDora, V
影响因子：
3.9
作者：
Kalinovich, Anastasia V.;de Jong, Jasper M. A.;Nedergaard, Jan
通讯作者：
Nedergaard, Jan
影响因子：
4.7
作者：
Hascup, Erin R.;Broderick, Sarah O.;Hascup, Kevin N.
通讯作者：
Hascup, Kevin N.