Mechanisms of stem cell preservation and lifespan extension in Drosophila
果蝇干细胞保存和寿命延长的机制
基本信息
- 批准号:9803243
- 负责人:
- 金额:$ 34.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-15 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAgingAnimal ModelAnimalsBehavioralBiological AssayCaenorhabditis elegansCandidate Disease GeneCuesDataDevelopmentDevelopmental GeneDiapauseDrosophila genusFeeding behaviorsFemaleFertilityGenesGeneticGenetic studyGoalsGrowthHumanIndividualInsulinInsulin ReceptorLongevityMaintenanceMetabolismMethodsMolecularMusOogenesisOrganismPathway interactionsProcessProxyPublic HealthRecoveryRegulationRejuvenationReproductionResistanceStem cellsStressSystemTemperatureTestingTimeLineTissuesWorkaxonal pathfindingcircadiancold temperatureday lengthexperiencefeedingfemale fertilityfertility preservationflyfollow-upgenetic approachgenome wide association studygermline stem cellshealthspaninsightknock-downmutantneurodevelopmentneuron developmentnovelnutrient deprivationpreservationprogramsreproductiveresponsetool
项目摘要
Across many species, including humans, one of the many consequences of aging is a
reduction in fertility, particularly female fertility. Intriguingly some species can preserve
fertility for longer than they otherwise would, under specific environmental conditions.
For example, various species of Drosophila enter a state called adult reproductive
diapause when they experience low temperatures and short day length. Under these
conditions they can double their lifespan while maintaining fertility. Previous work has
implicated a few genes in positive or negative regulation of adult reproductive diapause
in Drosophila. For example, the insulin pathway negatively regulates diapause,
suggesting mechanisms that are conserved with the regulation of metabolism, fertility,
and lifespan in other species including C. elegans, mice, and humans. However, our
mechanistic understanding of diapause is extremely limited, and how fertility is
preserved is unknown. We have taken advantage of powerful genetic tools in Drosophila
to carry out a genome-wide association study of diapause. This approach appears to be
highly successful, as the few known genes emerged from the analysis, such as the
insulin receptor. In addition, this screen revealed that the most highly enriched networks
of genes associated with diapause include those involved in neuronal development and
female reproduction. The neuronal development genes are striking, as they have not
previously been associated with diapause and thus offer to provide new molecular and
cellular insights. Here we propose to: 1) identify the genes controlling specific steps in
the diapause program such as entry, maintenance, exit, preservation of fecundity, and
lifespan; 2) test whether diapause genes are required during development to prepare the
animals for diapause, or function specifically in adulthood; and 3) investigate the
molecular mechanisms of germline stem cell preservation during diapause. We
anticipate that just as studies of C. elegans dauer formation illuminated general
pathways regulating metabolism, growth, reproduction and aging in animals ranging
from worms to humans, studies of Drosophila diapause offer the exciting potential to
uncover novel and general mechanisms of stem cell preservation, fertility maintenance,
and lifespan extension.
对于包括人类在内的许多物种来说,衰老的众多后果之一是
生育能力下降,尤其是女性生育能力。有趣的是,有些物种可以保存
在特定环境条件下,生育力比其他情况下的生育力更长。
例如,各种果蝇进入称为成体生殖的状态
当它们经历低温和短日照时会滞育。在这些之下
在保持生育能力的同时,他们可以使寿命加倍。之前的作品有
涉及一些基因对成年生殖滞育的正向或负向调节
在果蝇中。例如,胰岛素途径负向调节滞育,
表明与新陈代谢、生育力的调节有关的保守机制,
以及其他物种(包括秀丽隐杆线虫、小鼠和人类)的寿命。然而,我们的
对滞育机制的理解极其有限,以及生育力如何
保存情况不明。我们在果蝇中利用了强大的遗传工具
开展滞育的全基因组关联研究。这种方法似乎是
非常成功,因为分析中出现了少数已知基因,例如
胰岛素受体。此外,该屏幕显示最丰富的网络
与滞育相关的基因包括那些涉及神经元发育和
女性生殖。神经元发育基因是惊人的,因为它们没有
以前被认为与滞育有关,因此提供了新的分子和
细胞见解。在这里,我们建议:1)识别控制特定步骤的基因
滞育计划,例如进入、维持、退出、繁殖力保存和
寿命; 2) 测试发育过程中是否需要滞育基因来制备
滞育动物,或在成年期具有特定功能的动物; 3)调查
滞育期间生殖干细胞保存的分子机制。我们
预计正如对秀丽隐杆线虫 dauer 形成的研究所阐明的一般
调节动物新陈代谢、生长、繁殖和衰老的途径
从蠕虫到人类,果蝇滞育的研究提供了令人兴奋的潜力
揭示干细胞保存、生育能力维持的新颖和一般机制,
和寿命延长。
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 }}
Denise J. Montell其他文献
Editorial: Special issue SCDB "Cell death and survival": Cell death and resilience in health and disease.
社论:SCDB 特刊“细胞死亡与生存”:健康和疾病中的细胞死亡与恢复力。
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:7.3
- 作者:
Maddalena Nano;Denise J. Montell - 通讯作者:
Denise J. Montell
Denise J. Montell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('Denise J. Montell', 18)}}的其他基金
Mechanisms of stem cell preservation and lifespan extension in Drosophila
果蝇干细胞保存和寿命延长的机制
- 批准号:
10399509 - 财政年份:2019
- 资助金额:
$ 34.1万 - 项目类别:
Mechanisms of stem cell preservation and lifespan extension in Drosophila
果蝇干细胞保存和寿命延长的机制
- 批准号:
10625313 - 财政年份:2019
- 资助金额:
$ 34.1万 - 项目类别:
2015 Directed Cell Migration Gordon Research Conference & Gordon Research Seminar
2015年定向细胞迁移戈登研究会议
- 批准号:
8837312 - 财政年份:2015
- 资助金额:
$ 34.1万 - 项目类别:
Anastasis, a new mechanism driving cell survival and evolution
Anastasis,驱动细胞生存和进化的新机制
- 批准号:
8932673 - 财政年份:2014
- 资助金额:
$ 34.1万 - 项目类别:
Anastasis, a new mechanism driving cell survival and evolution
Anastasis,驱动细胞生存和进化的新机制
- 批准号:
9099812 - 财政年份:2014
- 资助金额:
$ 34.1万 - 项目类别:
Anastasis, a new mechanism driving cell survival and evolution
Anastasis,驱动细胞生存和进化的新机制
- 批准号:
8750779 - 财政年份:2014
- 资助金额:
$ 34.1万 - 项目类别:
Reversal of apoptosis:an in vivo mechanism for cytoprotection and mutagenesis
细胞凋亡的逆转:细胞保护和诱变的体内机制
- 批准号:
8720004 - 财政年份:2013
- 资助金额:
$ 34.1万 - 项目类别:
Reversal of apoptosis:an in vivo mechanism for cytoprotection and mutagenesis
细胞凋亡的逆转:细胞保护和诱变的体内机制
- 批准号:
8589289 - 财政年份:2013
- 资助金额:
$ 34.1万 - 项目类别:
相似国自然基金
生物炭原位修复底泥PAHs的老化特征与影响机制
- 批准号:42307107
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
光老化微塑料持久性自由基对海洋中抗生素抗性基因赋存影响机制
- 批准号:42307503
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
METTL3通过m6A甲基化修饰NADK2调节脯氨酸代谢和胶原合成影响皮肤光老化的机制研究
- 批准号:82360625
- 批准年份:2023
- 资助金额:32 万元
- 项目类别:地区科学基金项目
来源和老化过程对大气棕碳光吸收特性及环境气候效应影响的模型研究
- 批准号:42377093
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
河口潮滩中轮胎磨损颗粒的光老化特征及对沉积物氮素转化的影响与机制
- 批准号:42307479
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Uncovering Mechanisms of Racial Inequalities in ADRD: Psychosocial Risk and Resilience Factors for White Matter Integrity
揭示 ADRD 中种族不平等的机制:心理社会风险和白质完整性的弹性因素
- 批准号:
10676358 - 财政年份:2024
- 资助金额:
$ 34.1万 - 项目类别:
The Influence of Lifetime Occupational Experience on Cognitive Trajectories Among Mexican Older Adults
终生职业经历对墨西哥老年人认知轨迹的影响
- 批准号:
10748606 - 财政年份:2024
- 资助金额:
$ 34.1万 - 项目类别:
The Proactive and Reactive Neuromechanics of Instability in Aging and Dementia with Lewy Bodies
衰老和路易体痴呆中不稳定的主动和反应神经力学
- 批准号:
10749539 - 财政年份:2024
- 资助金额:
$ 34.1万 - 项目类别:
Understanding the Mechanisms and Consequences of Basement Membrane Aging in Vivo
了解体内基底膜老化的机制和后果
- 批准号:
10465010 - 财政年份:2023
- 资助金额:
$ 34.1万 - 项目类别:
REGULATION OF BONE MARROW MESENCHYMAL STEM CELLS BY VCAM1
VCAM1 对骨髓间充质干细胞的调节
- 批准号:
10537391 - 财政年份:2023
- 资助金额:
$ 34.1万 - 项目类别: