Aging regulation by non-autonomous signaling from Drosophila gut enteroendocrine cells
果蝇肠道内分泌细胞非自主信号传导的衰老调节
基本信息
- 批准号:10392963
- 负责人:
- 金额:$ 39.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgeAgingAnimalsBehaviorBiological AssayBiological ModelsBrainCell CommunicationCellsChestCoculture TechniquesCorpora AllataDataDietDigestionDistantDrosophila genusEnteroendocrine CellFat BodyG-Protein-Coupled ReceptorsGoalsGrowthHormonesHumanIndividualInsulinIntestinesJuvenile HormonesLipidsLongevityMammalsMeasuresMetabolismModelingMuscleNeuropeptidesNutrientOrganismPeptide ReceptorPeptidesPerformancePeripheralPhysiologyProductionProteinsRegulationReproductionSignal TransductionSignaling MoleculeSourceSystemTestingTissuesTranscriptional RegulationWorkage relatedcytokinedietary restrictionflygenetic approachgenetic manipulationgut microbiomehormonal signalsinsulin-like peptidemortalitynovelpeptide hormoneresponsestem cellstranscription factor
项目摘要
Signals produced by a few cells within a single tissue can regulate lifespan and functional aging throughout an
animal. These signaling molecules may exert nonautonomous effects at target tissues to induce their protective
mechanisms against age-dependent degeneration. Conversely, nonautonomous signals such as insulin/IGF-like
hormones may promote somatic functions that favor growth and reproduction, but while being permissive to
somatic degeneration. While nonautonomous signaling in aging regulation has been best characterized in terms
of centrally produced hormones, and more recently with cytokines and SASP, provocative data from several
model systems suggest there are critical, nonautonomous regulators of aging yet to be described. Accordingly,
this proposal focuses on small neuropeptide like molecules secreted from specialized cells of the intestine – gut
peptides. Enteroendocrine cells of animal guts, including those of Drosophila and humans, produce many gut
peptides that have system-wide impacts on behavior, digestion and metabolism. Working with Drosophila, we
propose that gut peptides can also affect lifespan and somatic functional aging by nonautonomous signaling
across the organism. In Drosophila, gut peptide production appears change with age, some increasing and
others decreasing. We also found that depleting a nutrient sensitive transcription factor in fly enteroendocrine
cells was sufficient to block longevity extension by dietary restriction, while inducing this factor appears to
increase the ability of dietary restriction to slow aging. We propose that gut peptides secreted from these cells
provides a mechanism to regulate aging and in particular in response to diet. The work has three objectives.
First is to fully characterize changes in the secretion of gut peptides from fly intestines with age and in response
to dietary restriction, and to assay their transcriptional controls. From our identified age-dynamic gut peptides,
we will use genetic manipulations to robustly infer which gut have the capacity to nonautonomously control life
span and functional aging at target tissues. The second goal is to determine if gut peptides modulate aging
through direct signaling at target tissues, and notably through G-Protein Coupled Receptors at these tissues.
The third aim explores if gut peptides nonautonomously modulate aging by affecting production of a secondary,
relay hormone, such as insulin/IGF or juvenile hormone, which in turn control systemic functional aging. Together
these aims will describe a novel tissue function for the intestine in aging control through systemic signaling, and
provide a model to explore these highly conserved gut peptides in mammals during aging and in response to
dietary restriction.
由单个组织中的几个细胞产生的信号可以在整个过程中调节寿命和功能老化。
动物这些信号分子可能在靶组织中发挥非自主作用,诱导其保护作用。
对抗年龄依赖性退化的机制。相反,非自主信号,如胰岛素/IGF-样
激素可以促进有利于生长和繁殖的躯体功能,但同时允许
躯体退化虽然非自主信号在老化调节中的最佳特征是
中枢产生的激素,最近与细胞因子和SASP,挑衅性的数据,从几个
模型系统表明,还有一些关键的、非自主的老化调节器有待描述。因此,委员会认为,
这项建议集中于从肠的特化细胞分泌的小神经肽样分子。
缩氨酸动物肠道的肠内分泌细胞,包括果蝇和人类的肠内分泌细胞,
对行为、消化和代谢具有系统性影响的肽。通过研究果蝇,
我认为肠道肽也可以通过非自主信号传导影响寿命和躯体功能老化
在整个有机体中。在果蝇中,肠道肽的产生随着年龄的增长而变化,有些增加,
其他人减少。我们还发现,在果蝇肠内分泌系统中,
细胞足以阻止通过饮食限制延长寿命,而诱导这种因素似乎
增加饮食限制延缓衰老的能力。我们认为这些细胞分泌的肠肽
提供了一种调节衰老的机制,特别是对饮食的反应。这项工作有三个目标。
首先是充分表征苍蝇肠道分泌的肠道肽随年龄的变化和响应
饮食限制,并测定其转录控制。从我们确定的年龄动态肠道肽,
我们将使用基因操作来有力地推断哪种肠道具有非自主控制生命的能力
靶组织的跨度和功能老化。第二个目标是确定肠道肽是否调节衰老
通过靶组织的直接信号传导,特别是通过这些组织的G蛋白偶联受体。
第三个目的是探索肠道肽是否通过影响次级代谢产物的产生来非自主地调节衰老,
中继激素,如胰岛素/IGF或保幼激素,其反过来控制系统功能性衰老。一起
这些目的将描述通过系统信号传导在衰老控制中肠的新组织功能,
提供了一个模型,以探索这些高度保守的肠道肽在哺乳动物在衰老过程中,并在响应
饮食限制
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 }}
MARC TATAR其他文献
MARC TATAR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('MARC TATAR', 18)}}的其他基金
Genome wide association analysis with Drosophila to discover how metformin effects longevity
与果蝇的全基因组关联分析,以发现二甲双胍如何影响长寿
- 批准号:
10085915 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Genome wide association analysis with Drosophila to discover how metformin effects longevity
与果蝇的全基因组关联分析,以发现二甲双胍如何影响长寿
- 批准号:
10645126 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Innate immune dysregulation in Alzheimer's disease modeled in Drosophila
以果蝇为模型的阿尔茨海默病的先天免疫失调
- 批准号:
10259828 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Genome wide association analysis with Drosophila to discover how metformin effects longevity
与果蝇的全基因组关联分析,以发现二甲双胍如何影响长寿
- 批准号:
10424563 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Genome wide association analysis with Drosophila to discover how metformin effects longevity
与果蝇的全基因组关联分析,以发现二甲双胍如何影响长寿
- 批准号:
10264139 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Aging regulation by non-autonomous signaling from Drosophila gut enteroendocrine cells
果蝇肠道内分泌细胞非自主信号传导的衰老调节
- 批准号:
9920655 - 财政年份:2018
- 资助金额:
$ 39.26万 - 项目类别:
REPTOR as a mechanism for aging control by dietary restriction and rapamycin
REPTOR作为通过饮食限制和雷帕霉素控制衰老的机制
- 批准号:
9299810 - 财政年份:2017
- 资助金额:
$ 39.26万 - 项目类别:
FUNCTIONS AND INTERACTIONS DFOXO IN DROSOPHILA AGING
DFOXO 在果蝇衰老中的功能和相互作用
- 批准号:
9901409 - 财政年份:2016
- 资助金额:
$ 39.26万 - 项目类别:
相似海外基金
Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
- 批准号:
495182 - 财政年份:2023
- 资助金额:
$ 39.26万 - 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
- 批准号:
2601817 - 财政年份:2021
- 资助金额:
$ 39.26万 - 项目类别:
Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
- 批准号:
2029039 - 财政年份:2020
- 资助金额:
$ 39.26万 - 项目类别:
Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
- 批准号:
9888417 - 财政年份:2019
- 资助金额:
$ 39.26万 - 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
- 批准号:
17K11318 - 财政年份:2017
- 资助金额:
$ 39.26万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9320090 - 财政年份:2017
- 资助金额:
$ 39.26万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
10166936 - 财政年份:2017
- 资助金额:
$ 39.26万 - 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
- 批准号:
9761593 - 财政年份:2017
- 资助金额:
$ 39.26万 - 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
- 批准号:
BB/M50306X/1 - 财政年份:2014
- 资助金额:
$ 39.26万 - 项目类别:
Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
- 批准号:
288272 - 财政年份:2013
- 资助金额:
$ 39.26万 - 项目类别:
Miscellaneous Programs