Effect of dietary restriction on intestinal stem cell aging
饮食限制对肠道干细胞衰老的影响
基本信息
- 批准号:10823900
- 负责人:
- 金额:$ 23.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAffectAgeAgingBiological AgingBiological MarkersBloodBone MarrowBrainC57BL/6 MouseCell CountCell Differentiation InductionCell Differentiation processCell SeparationCell physiologyCellsChromatinCognitionCytosineDNADNA MethylationDNA Modification MethylasesDNA-Binding ProteinsDataData AnalysesDecelerationDevelopmentDietDioxygenasesDiseaseEnhancersEnzymesEpigenetic ProcessEpithelial CellsEquilibriumExposure toFemaleFutureGene ExpressionGenesGenetic Enhancer ElementGenomeGenomicsGeroscienceGrantHippocampusIn VitroInterventionIntestinal MucosaIntestinesInvertebratesKidneyKnowledgeLaboratoriesLifeLiverLongevityMaintenanceMeasuresMediatingMemoryMessenger RNAMethylationMitogensMolecularMucous MembraneMusMuscleNatural regenerationNeurotensinOrganismPathway interactionsPhysiologicalPhysiological ProcessesPlayPositioning AttributeProcessProliferatingPromoter RegionsRattusRegenerative capacityRegulationReportingResolutionRodentRoleSiteTestingTimeTissuesUnited States National Institutes of HealthWorkadult stem cellage effectage relatedagedanti agingbasedata integrationdemethylationdietary restrictionepigenetic regulationfunctional declinegenome-wideimprovedinsightintestinal epitheliummalemethylation patternmouse genomenerve stem cellneurogenesisnonhuman primatepreventpromoterregeneration potentialsexstem cell agingstem cell differentiationstem cell functionstem cell genesstem cell proliferationstem cell self renewalstem cellstheoriestranscription factortranscriptometranscriptome sequencingtranscriptomicswhole genome
项目摘要
Stem cells play a critical role in the maintenance of tissue function with age and retention of their
regenerative capacity is essential to this role. An age-related decline in regenerative capacities
due to loss of stem cell number and function is observed in many tissues. Therefore,
understanding the mechanism(s) that regulates stem cell function is essential for retarding the
aging process and interventions that affect stem cells have the potential to be a target for antiaging
interventions. Dietary restriction (DR) is a robust anti-aging intervention that extends the
lifespan of a variety of organisms and has been shown to prevent the decline in physiological
function. DR has been shown to enhance the function and self-renewal of stem cells in various
tissues including the intestinal stem cells. Studies indicate that both long and short term DR
increases intestinal stem cell number and the ability of the stem cells to regenerate an entire crypt
in vitro. Although DR has been shown to enhance the regenerative capacity of intestinal stem
cells, the mechanism underlying this effect remains unknown. DNA methylation has been shown
to have a critical role in stem cell proliferation and differentiation. More importantly, DNA
methylation drift has been associated with stem cell aging. Based on these key studies and our
recent preliminary data, we hypothesize that, DR increases the expression of genes involved
in ISCs proliferation and differentiation by inducing changes in DNA methylation at
specific genomic sites of the ISCs. Further, we propose that short term DR will reverse the
age-related decline in stem cell aging by modifying both DNA methylation and gene
expression. We will test our hypothesis through these aims: (i) Identify DNA methylation
changes induced by DR in the ISC genome (ii) Identify key genes that play a role in DR’s effect
on ISC function.
随着年龄的增长,干细胞在维持组织功能方面发挥着关键作用
再生能力对这一角色至关重要。与年龄相关的再生能力下降
由于干细胞数量和功能的丧失,在许多组织中都可以观察到。因此,
了解干细胞功能的调节机制(S)对于延缓
影响干细胞的衰老过程和干预措施有可能成为抗衰老的目标
干预措施。饮食限制(DR)是一种强有力的抗衰老干预措施,它延长了
多种生物体的寿命,并已被证明可以防止生理上的衰退
功能。DR已被证明能增强干细胞的功能和自我更新能力
包括肠道干细胞在内的组织。研究表明,无论是长期还是短期DR
增加肠道干细胞数量和干细胞再生整个隐窝的能力
在试管中。虽然DR已被证明可以增强肠道干细胞的再生能力
细胞,这种效应背后的机制尚不清楚。DNA甲基化已被证明
在干细胞增殖和分化中起关键作用。更重要的是,DNA
甲基化漂移与干细胞老化有关。基于这些关键研究和我们的
最近的初步数据,我们假设,DR增加了相关基因的表达
通过诱导DNA甲基化改变在ISCs增殖和分化中的作用
ISCs的特定基因组位置。此外,我们建议短期DR将逆转
通过改变DNA甲基化和基因来降低干细胞的老化程度
表情。我们将通过这些目标来检验我们的假设:(I)识别DNA甲基化
ISC基因组中DR引起的变化(II)确定在DR效应中起作用的关键基因
论ISC的功能。
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 }}
Archana Unnikrishnan其他文献
Archana Unnikrishnan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('Archana Unnikrishnan', 18)}}的其他基金
Role of DNA Methylation in Dietary Restriction mediated insulin sensitivity
DNA 甲基化在饮食限制介导的胰岛素敏感性中的作用
- 批准号:
10447812 - 财政年份:2018
- 资助金额:
$ 23.22万 - 项目类别:
Role of DNA Methylation in Dietary Restriction mediated insulin sensitivity
DNA 甲基化在饮食限制介导的胰岛素敏感性中的作用
- 批准号:
10207427 - 财政年份:2018
- 资助金额:
$ 23.22万 - 项目类别:
Role of DNA Methylation in Dietary Restriction mediated insulin sensitivity
DNA 甲基化在饮食限制介导的胰岛素敏感性中的作用
- 批准号:
9789794 - 财政年份:2018
- 资助金额:
$ 23.22万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 23.22万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
$ 23.22万 - 项目类别:
Standard Grant