• 生物技术的进步为个性化医疗和精准治疗提供了可能。
  • 在线教育的普及为全球学习者提供了前所未有的学习机会。
  • 自动化和机器人技术在制造业中的应用提高了生产效率。
  • 随着在线教育的兴起,教育公平问题再次成为社会讨论的热点。
  • 数字化转型正在加速,企业必须适应这一变化以保持竞争力。
  • 人工智能在医疗诊断和治疗中的应用正在改善患者的治疗效果。
  • 全球健康危机促使各国加强公共卫生体系的建设和改革。
  • 海洋塑料污染问题引起了全球范围内的环保行动和政策调整。
  • 电动汽车的普及推动了能源行业的转型,减少了对化石燃料的依赖。
  • 远程工作模式的普及引发了对工作生活平衡和城市居住模式的新思考。
  • 隐私保护和数据安全在数字化时代变得更加重要。
  • 智能家居设备的发展正在使家庭生活更加便捷和个性化。
  • 在线教育的普及为全球学习者提供了更广泛的学习机会。
  • 智能家居设备使日常生活更加便捷,推动了居住环境的智能化。
  • 电子竞技的流行正在改变体育和娱乐行业的格局。
  • 随着人们对健康生活的追求,运动科技和穿戴设备市场正在快速增长。
  • 大数据和机器学习在商业智能和市场分析中发挥关键作用。
  • 随着全球经济不确定性增加,跨国公司的社会责任和环境影响受到更多审视。
  • 电子商务的快速发展正在重塑全球零售和供应链管理。
  • 虚拟现实技术在教育和娱乐领域的应用越来越广泛。
  • 全球健康危机凸显了加强公共卫生体系和国际卫生合作的紧迫性。
  • 隐私保护和数据安全在数字化时代变得更加重要。
  • 随着太空探索的进展,商业航天领域迎来了新的发展机遇。
  • 电动汽车的普及推动了能源行业的绿色转型。
  • 太空探索的商业化为航天产业带来了新的增长点。
  • Sex-dependent lifespan extension of ApcMin/+ FAP mice by chronic mTOR inhibition | Parihar | Aging Pathobiology and Therapeutics

    Sex-dependent lifespan extension of ApcMin/+ FAP mice by chronic mTOR inhibition

    Manish Parihar, Sherry G Dodds, Marty Javors, Randy Strong, Paul Hasty, Zelton Dave Sharp

    Abstract


    Background: ApcMin/+ mice model familial adenomatous polyposis (FAP), a disease that causes numerous colon polyps leading to colorectal cancer. We previously showed that chronic treatment of ApcMin/+ females with the anti-aging drug, rapamycin, restored a normal lifespan through reduced polyposis and anemia prevention. Lifespan extension by chronic rapamycin in wildtype UM-HET3 mice is sex-dependent with females gaining the most benefit. Whether ApcMin/+ mice have a similar sex-dependent response to chronic mTOR inhibition is not known.

    Methods: To address this knowledge gap and gain deeper insight into how chronic mTOR inhibition prevents intestinal polyposis, we compared male and female ApcMin/+ mice responses to chronic treatment with a rapamycin-containing diet. Animals were fed a diet containing either 42 ppm microencapsulate rapamycin or empty capsules, one group was used to determine lifespan and a second group with similar treatment was harvested at 16 weeks of age for cross-sectional studies.

    Results: We found that the survival of males is greater than females in this setting (P < 0.0197). To explore the potential basis for this difference we analyzed factors affected by chronic rapamycin. Immunoblot assays showed that males and females exhibited approximately the same level of mTORC1 inhibition using phosphorylation of ribosomal protein S6 (rpS6) as an indirect measure. Immunohistochemistry assays of rpS6 phosphorylation showed that rapamycin reduction of mTORC1 activity was on the same level, with the most prominent difference being in intestinal crypt Paneth cells in both sexes. Chronic rapamycin also reduced crypt depths in both male and female ApcMin/+ mice (P < 0.0001), consistent with reduced crypt epithelial cell proliferation. Finally, chronic rapamycin prevented anemia equally in males and females.

    Conclusions: In males and females, these findings link rapamycin-mediated intestinal polyposis prevention with mTORC1 inhibition in Paneth cells and concomitant reduced epithelial cell proliferation.

    Keywords: Rapamycin, small intestine, polyposis, mTORC1, Paneth cells, crypt stem cells




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