Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol

17a-雌二醇增强代谢、炎症和健康寿命的机制

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT The research and career development activities outlined in this application have been designed to equip the candidate, Dr. Michael Stout, with the scientific and technical expertise necessary to become an independent investigator. The proposed research aims to elucidate the mechanisms responsible for the alleviation of age- related metabolic and inflammatory dysfunction by 17α-estradiol and identify the receptor(s)/pathway(s) by which these effects occur. As such, the candidate will receive additional training in signaling networks directly relevant to this area of research through intensive coursework and hands-on laboratory experience under the supervision of Drs. James Kirkland, Eduardo Chini, and Sundeep Khosla. The short-term objectives of this application are to enhance the candidate's knowledge of nutrient-sensing and inflammatory pathway interactions and develop technical skills to evaluate these relationships in culture- and animal-model systems. The long-term goals of this application are to enable the candidate, as a newly-hired faculty member, to secure protected time for research activities, establish new collaborations, and develop a novel line of research that produces competitive grant proposals for future funding. Preliminary studies performed by the candidate under the direction of Dr. James Kirkland indicate that 17α-estradiol enhances metabolic function and alleviates inflammation in older mice through pathways that are central to metabolic homeostasis and the aging process. This proposal will expand upon these findings by unraveling the intracellular mechanisms responsible for these phenotypes while also identifying receptor(s)/pathway(s) by which 17α-estradiol elicits these downstream effects. The overall hypothesis is that 17α-estradiol signals through an uncharacterized receptor/pathway leading to activation of AMPK and alleviation of metabolic and inflammatory dysfunction. The candidate will test this hypothesis through the following aims: 1) Determine if metabolic enhancement by 17α-estradiol is AMPK-dependent; 2) Determine if 17α-estradiol reduces inflammation by suppressing mTOR and/or NFKB; and 3) Identify the receptor(s)/pathway(s) by which 17α-estradiol elicits its cellular effects. This work will significantly enhance the understanding of molecular and cellular pathways by which 17α-estradiol elicits its effects which could lead to the development of novel treatments for aging- and/or obesity-related metabolic and inflammatory disorders.
项目总结/文摘

项目成果

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Michael B Stout其他文献

Michael B Stout的其他文献

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{{ truncateString('Michael B Stout', 18)}}的其他基金

Role of estrogen receptor-a in aging and sex-specific responses to 17a-estradiol
雌激素受体-a 在衰老和对 17a-雌二醇的性别特异性反应中的作用
  • 批准号:
    10470024
  • 财政年份:
    2021
  • 资助金额:
    $ 24.84万
  • 项目类别:
Role of estrogen receptor-a in aging and sex-specific responses to 17a-estradiol
雌激素受体-a 在衰老和对 17a-雌二醇的性别特异性反应中的作用
  • 批准号:
    10662459
  • 财政年份:
    2021
  • 资助金额:
    $ 24.84万
  • 项目类别:
Role of estrogen receptor-a in aging and sex-specific responses to 17a-estradiol
雌激素受体-a 在衰老和对 17a-雌二醇的性别特异性反应中的作用
  • 批准号:
    10294797
  • 财政年份:
    2021
  • 资助金额:
    $ 24.84万
  • 项目类别:
Cellular senescence and epigenomic remodeling in ovarian aging
卵巢衰老中的细胞衰老和表观基因组重塑
  • 批准号:
    10417250
  • 财政年份:
    2020
  • 资助金额:
    $ 24.84万
  • 项目类别:
Cellular senescence and epigenomic remodeling in ovarian aging
卵巢衰老中的细胞衰老和表观基因组重塑
  • 批准号:
    10656200
  • 财政年份:
    2020
  • 资助金额:
    $ 24.84万
  • 项目类别:
Cellular senescence and epigenomic remodeling in ovarian aging
卵巢衰老中的细胞衰老和表观基因组重塑
  • 批准号:
    10470674
  • 财政年份:
    2020
  • 资助金额:
    $ 24.84万
  • 项目类别:
Cellular senescence and epigenomic remodeling in ovarian aging
卵巢衰老中的细胞衰老和表观基因组重塑
  • 批准号:
    10091665
  • 财政年份:
    2020
  • 资助金额:
    $ 24.84万
  • 项目类别:
Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol
17a-雌二醇增强代谢、炎症和健康寿命的机制
  • 批准号:
    9790886
  • 财政年份:
    2018
  • 资助金额:
    $ 24.84万
  • 项目类别:
Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol
17a-雌二醇增强代谢、炎症和健康寿命的机制
  • 批准号:
    9336760
  • 财政年份:
    2016
  • 资助金额:
    $ 24.84万
  • 项目类别:

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