FSH - an Aging Hormone?

FSH——一种衰老激素?

基本信息

项目摘要

PROGRAM SUMMARY Obesity and osteoporosis are global public health hazards that commonly affect older individuals and often co-exist in postmenopausal women. While a restricted armamentarium of therapies is available for osteoporosis, the five approved agents for obesity are limited by poor efficacy and unacceptable side effects. Hence, new approaches to treat these two chronic conditions of aging require a collaborative and rigorous integrative program between independent, but fully interactive laboratories. This U19 builds on a firm foundation of rigorous and transparent research, born from a longstanding collaboration between Drs. Mone Zaidi and Clifford Rosen, the results of which were published last year (Nature, 2017, PMID: 28538730). We identified FSH as a unique target to prevent both obesity and osteoporosis. We raised a polyclonal antibody to Fshβ, which, by blocking its access to the Fsh receptor (Fshr), prevented high-fat-diet-induced obesity and ovariectomy-induced osteoporosis. In addition, our Fsh antibody triggered the appearance of energy- producing ‘beige’ adipocytes in white adipose tissue. Based on these studies and others, we now postulate that FSH may also be a critical aging hormone. We therefore propose to undertake a comprehensive, multipronged and interdisciplinary study of the effects of blocking Fsh signaling, either pharmacologically using our monoclonal anti-Fsh antibodies or genetically in Fshr-/- mice, on lifespan, fat gain, bone marrow adiposity, and skeletal health in mice. We will also study the mechanism of Fsh action on fat cells using ThermoMice that report ‘beiging,’ AdipoChaser mice that measure de novo adipogenesis, and state-of-the-art technologies for transcriptome, lipidome and bioenergetic profiling. To buttress our preclinical observations and, with a view of testing our monoclonal antibodies in people, we propose an epidemiological study of older women and men in the AGES-Reykjavik Cohort. We will examine whether serum FSH can be used as a surrogate marker for bone loss, visceral fat gain, bone marrow adiposity, and ultimately, fracture risk. To provide necessary resources across the four investigative sites–Icahn School of Medicine at Mount Sinai, Maine Medical Center Research Institute, University of Texas Southwestern Medical Center and the University of California at San Francisco–we propose three overarching multifunctional cores: a Skeletal and Metabolic Phenotyping Core, an Antibody Production and Testing Core, and an Administrative and Biostatistics Support Core. In sum, our U19 proposal should allow us to break new ground in our understanding of two prevalent disorders of aging, in addition to opening new avenues for therapeutic interventions for our increasing numbers of older adults.
计划概要 肥胖和骨质疏松症是全球公共卫生危害,通常影响老年人和老年人 常并存于绝经后妇女。虽然治疗方法有限 骨质疏松症方面,五种已批准的治疗肥胖症的药物因疗效不佳和不可接受的副作用而受到限制。 因此,治疗这两种慢性衰老疾病的新方法需要合作和严格的 独立但完全互动的实验室之间的综合计划。这支U19建立在坚定的基础上 严格而透明的研究基础,源于博士之间的长期合作。莫内 Zaidi 和 Clifford Rosen,其结果于去年发表(Nature,2017,PMID:28538730)。我们 确定 FSH 是预防肥胖和骨质疏松症的独特目标。我们提出了一种多克隆抗体 Fshβ,通过阻断其与 Fsh 受体 (Fshr) 的接触,预防高脂肪饮食引起的肥胖, 卵巢切除术引起的骨质疏松症。此外,我们的 Fsh 抗体引发了能量- 在白色脂肪组织中产生“米色”脂肪细胞。基于这些研究和其他研究,我们现在假设 FSH 也可能是一种重要的衰老激素。因此,我们建议开展全面的、 对阻断 Fsh 信号传导效果的多管齐下和跨学科研究,无论是药理学上还是使用 我们的单克隆抗 Fsh 抗体或 Fshr-/- 小鼠的基因抗体,对寿命、脂肪增加、骨髓肥胖、 和小鼠骨骼健康。我们还将使用 ThermoMice 研究 Fsh 对脂肪细胞的作用机制 报告“beiging”的 AdipoChaser 小鼠测量脂肪从头生成,以及最先进的技术 用于转录组、脂质组和生物能量分析。支持我们的临床前观察,并着眼于 为了在人体中测试我们的单克隆抗体,我们建议对老年女性和男性进行流行病学研究 在 AGES-雷克雅未克队列中。我们将检查血清 FSH 是否可以作为替代标记物 骨质流失、内脏脂肪增加、骨髓肥胖,以及最终的骨折风险。提供必要的 四个研究地点的资源——西奈山伊坎医学院缅因州医疗中心 德克萨斯大学西南医学中心和加州大学圣路易斯分校研究所 Francisco——我们提出了三个总体多功能核心:骨骼和代谢表型核心、 抗体生产和测试核心,以及行政和生物统计支持核心。综上所述,我们的U19 该提案应该使我们能够在理解两种普遍的衰老疾病方面开辟新的天地, 除了为越来越多的老年人开辟新的治疗干预途径之外。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CLIFFORD JAMES ROSEN其他文献

CLIFFORD JAMES ROSEN的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CLIFFORD JAMES ROSEN', 18)}}的其他基金

Northern New England Clinical and Translational Research Network
新英格兰北部临床和转化研究网络
  • 批准号:
    10681809
  • 财政年份:
    2021
  • 资助金额:
    $ 229.85万
  • 项目类别:
Understanding Factors Influencing COVID-19 Testing and Vaccination in Immigrant Low-income and Homeless Populations and Testing Targeted Interventions
了解影响移民低收入和无家可归人群的 COVID-19 检测和疫苗接种的因素以及测试有针对性的干预措施
  • 批准号:
    10413438
  • 财政年份:
    2021
  • 资助金额:
    $ 229.85万
  • 项目类别:
FSH - an Aging Hormone?
FSH——一种衰老激素?
  • 批准号:
    10112794
  • 财政年份:
    2019
  • 资助金额:
    $ 229.85万
  • 项目类别:
FSH - an Aging Hormone?
FSH——一种衰老激素?
  • 批准号:
    10577830
  • 财政年份:
    2019
  • 资助金额:
    $ 229.85万
  • 项目类别:
Physiology Core
生理学核心
  • 批准号:
    10711694
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10891897
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:
Northern New England Clinical and Translational Research Network
新英格兰北部临床和转化研究网络
  • 批准号:
    10675577
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:
Northern New England Clinical and Translational Research Network-Equipment
新英格兰北部临床和转化研究网络设备
  • 批准号:
    10797663
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10871636
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10505150
  • 财政年份:
    2017
  • 资助金额:
    $ 229.85万
  • 项目类别:

相似海外基金

Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
  • 批准号:
    MR/Y013891/1
  • 财政年份:
    2024
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
  • 批准号:
    BB/Y006542/1
  • 财政年份:
    2024
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Research Grant
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
  • 批准号:
    23H03323
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
  • 批准号:
    23K08293
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
  • 批准号:
    479570
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
  • 批准号:
    488898
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Operating Grants
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
  • 批准号:
    23K19922
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
A mechanism of lipid accumulation in brown adipose tissue
棕色脂肪组织中脂质积累的机制
  • 批准号:
    10605981
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
  • 批准号:
    10813753
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
  • 批准号:
    10604611
  • 财政年份:
    2023
  • 资助金额:
    $ 229.85万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了