Using cellular co-biosis and age programmable mice to derive a global interaction map of aging hallmarks
Using cellular co-biosis and age programmable mice to derive a global interaction map of aging hallmarks
批准号:
10721454
负责人:
DAVID A. SINCLAIR
金额:
$45.36万
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
项目状态:
未结题
起止时间:
2023-09-15 至 2028-05-31
关键词:
3-DimensionalATAC-seqAccelerationAffectAgeAgingAppearanceArchitectureAttenuatedBiologicalBiologyCategoriesCell NucleusCell physiologyCellsComplexComputer softwareCytoplasmDNADNA MethylationDNA methylation profilingDataDiseaseEnsureEpigenetic ProcessFeedbackFemaleGeneticGenetic VariationGenomeGenome MappingsGenomic SegmentHealthHumanHybridsImageImpairmentIncidenceIndividualInstructionInterventionKnowledgeMachine LearningMammalsMapsMeasuresMitochondriaMonitorMusNuclearOrganPhysiologicalProcessRNAReporterReportingStructureSystemTechnologyTestingTimeTissue HarvestingTissuesWorkage relatedagedattenuationbiological systemscell typedemethylationepigenomeepigenomicsin vivoindexinginducible gene expressioninnovationinsightlive cell imagingmalemethylation patternmultiple omicsnovelpathological agingprogramssensor technologysiRNA deliverysingle-cell RNA sequencingsoftware developmenttime usetoolultra high resolution
中文摘要
项目总结
生物系统被认为会随着时间的推移而失效,这是基于九个“衰老的标志”,它们不知何故导致了
全球范围内组织功能和健康的下降。基于这一范例、干预以及它们的组合,
正在开发中,以减弱每一个特征,并减缓衰老过程。不幸的是,缺乏
对这些老化特征之间相互依赖的洞察,使其难以普遍发展
有效的缓解战略。我们的实验室和其他实验室提供的证据表明,存储信息的丢失
损害细胞机械和身体结构的功能,导致衰老和与年龄相关的疾病。
我们已经开发了ICE系统(Yang et al.2022,由Cell临时接受),允许空间
以及对哺乳动物表观遗传衰老的时间控制。我们还发现,部分重新编程
使用重新编程因子Oct4、Sox2和Klf4(OSK),允许细胞检索年轻的
重置表观基因组、逆转多种衰老标志、恢复DNA甲基化的信息
模式恢复到他们以前的年轻状态(Lu等人,2020;Yang等人,2022,暂时被Cell接受)。
在这项研究中,我们利用我们在正向和反向控制衰老速度的能力来测试
假设细胞信息和细胞机械和物理之间的互连丧失
结构是衰老特征的主要驱动因素,也是衰老本身的可逆原因。要做到这一点,我们将
开发第一套荧光标记记者,以监控标记进展和在
并找到促进其共同逆转的方法。这一新工具将与先进的多用途计算机一起使用
新共生系统的组学方法和异质UM-HET3中可编程年龄的小鼠
遗传背景。
这项研究很重要,因为它将为长期存在的关于
老化标志之间的相互联系,例如是否存在等级制度以及如果一个标志的逆转
确保抹去他人的记忆。总之,这项工作将为现场提供一套新颖的可定制工具,以
跟踪和研究这些特征,并检验许多特征在信息级别相交的假设
因此,当核中的信息被重置到年轻状态时,它们是共同可逆的。
英文摘要
PROJECT SUMMARY
Biological systems are presumed to fail over time based on nine “hallmarks of aging,” which somehow cause a
global decline in tissue function and health. Based on this paradigm, interventions, and combinations of them,
are being developed to attenuate each of the hallmarks and slow the aging process. Unfortunately, a lack of
insight into the interdependence among these aging hallmarks has made it difficult to develop universally
effective mitigation strategies. Our lab and others have provided evidence that a loss of stored information
impairs the function of cellular machinery and physical structures, leading to aging and age-related diseases.
We have developed the ICE system (Yang et al. 2022, provisionally accepted by Cell) which allows for spatial
and temporal control over epigenetic aging in mammals. We have also discovered that partial reprogramming
using the reprogramming factors, Oct4, Sox2, and Klf4 (OSK), allows cells to retrieve a “backup copy” of youthful
information that resets the epigenome, reverses multiple hallmarks of aging, and restores DNA methylation
patterns to their previous youthful state (Lu et al., 2020; Yang et al., 2022, provisionally accepted by Cell).
In this study, we leverage our ability to control the pace of aging in forward and reverse directions to test the
hypothesis that a loss of interconnectivity between cellular information and cellular machinery and physical
structures is a primary driver of the Hallmarks of Aging and a reversible cause of aging itself. To do this, we will
develop the first set of fluorescent hallmark reporters to monitor hallmark progression and interactions during
aging and discover ways to promote their co-reversal. This novel tool will be utilized along with advanced multi-
omic approaches in novel co-biosis systems and age-programmable mice in the heterogeneous UM-HET3
genetic background.
This study is important because it will provide valuable knowledge concerning the long-standing questions about
interconnectivity among the aging hallmarks, such as whether hierarchies exist and if the reversal of one hallmark
ensures the erasure of others. Together, this work will provide the field with a novel set of customizable tools to
track and study these hallmarks and test the hypothesis that many hallmarks intersect at the informational level
and are therefore co-reversible when information in the nucleus is reset to a youthful state.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Tagmentation-based Indexing for Methylation Sequencing as a novel method of high-throughput methylation clock measurement
-
批准号:10273233
-
项目类别:
-
资助金额:$62.63万
-
财政年份:2021
-
负责人:DAVID A. SINCLAIR
-
依托单位:
Nicotinamide Mononucleotide (NMN) as a Novel Therapeutic in the Treatment of Oral Mucositis
-
批准号:9770831
-
项目类别:
-
资助金额:$21.19万
-
财政年份:2018
-
负责人:DAVID A. SINCLAIR
-
依托单位:
Uncovering the Human Secretome
-
批准号:9344966
-
项目类别:
-
资助金额:$118.65万
-
财政年份:2017
-
负责人:DAVID A. SINCLAIR
-
依托单位:
Uncovering the Human Secretome
-
批准号:10223179
-
项目类别:
-
资助金额:$118.65万
-
财政年份:2017
-
负责人:DAVID A. SINCLAIR
-
依托单位:
Uncovering the Human Secretome
-
批准号:9751141
-
项目类别:
-
资助金额:$118.65万
-
财政年份:2017
-
负责人:DAVID A. SINCLAIR
-
依托单位:
Elucidating mechanisms of SIRT1 activation
-
批准号:9315825
-
项目类别:
-
资助金额:$50.83万
-
财政年份:2016
-
负责人:DAVID A. SINCLAIR
-
依托单位:
2009 Biology of Aging Gordon Research Conference
-
批准号:7613586
-
项目类别:
-
资助金额:$5.0万
-
财政年份:2008
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT as a regulator of health and lifespan of mammals
-
批准号:7383794
-
项目类别:
-
资助金额:$33.95万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT as a regulator of health and lifespan of mammals
-
批准号:7589667
-
项目类别:
-
资助金额:$34.03万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT as a regulator of health and lifespan of mammals
-
批准号:8048190
-
项目类别:
-
资助金额:$32.4万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:9268167
-
项目类别:
-
资助金额:$44.92万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT as a regulator of health and lifespan of mammals
-
批准号:7260016
-
项目类别:
-
资助金额:$34.67万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:10116232
-
项目类别:
-
资助金额:$37.38万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:9884526
-
项目类别:
-
资助金额:$40.01万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:9101926
-
项目类别:
-
资助金额:$42.12万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:8723013
-
项目类别:
-
资助金额:$42.12万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:8534005
-
项目类别:
-
资助金额:$39.8万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT as a regulator of health and lifespan of mammals
-
批准号:7797997
-
项目类别:
-
资助金额:$33.71万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
SIRT1 as a regulator of health and lifespan of mammals
-
批准号:8387561
-
项目类别:
-
资助金额:$43.24万
-
财政年份:2007
-
负责人:DAVID A. SINCLAIR
-
依托单位:
THE BIOLOGY AND UTILITY SIRT1- MEDIATED NEUROPROTECTION
-
批准号:7085094
-
项目类别:
-
资助金额:$31.12万
-
财政年份:2006
-
负责人:DAVID A. SINCLAIR
-
依托单位:
国内基金
海外基金
登录
查看更多内容
基于ATAC-seq与DNA甲基化测序探究染色质可及性对莲两生态型地下茎适应性分化的作用机制
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:
-
依托单位:
利用ATAC-seq联合RNA-seq分析TOP2A介导的HCC肿瘤细胞迁移侵
袭的机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:柳静
-
依托单位:
面向图神经网络ATAC-seq模体识别的最小间隔单细胞聚类研究
-
批准号:62302218
-
项目类别:青年科学基金项目
-
资助金额:30.00万元
-
批准年份:2023
-
负责人:张双全
-
依托单位:
基于ATAC-seq策略挖掘穿心莲基因组中调控穿心莲内酯合成的增强子
-
批准号:--
-
项目类别:地区科学基金项目
-
资助金额:33万元
-
批准年份:2022
-
负责人:黄铭坤
-
依托单位:
基于单细胞ATAC-seq技术的C4光合调控分子机制研究
-
批准号:32100438
-
项目类别:青年科学基金项目(C类)
-
资助金额:30.0万元
-
批准年份:2021
-
负责人:涂晓雨
-
依托单位:
基于ATAC-seq技术研究交叉反应物质197调控TFEB介导的自噬抑制子宫内膜异位症侵袭的分子机制
-
批准号:82001520
-
项目类别:青年科学基金项目
-
资助金额:24.0万元
-
批准年份:2020
-
负责人:汤小晗
-
依托单位:
靶向治疗动态调控肺癌细胞DNA可接近性的ATAC-seq分析
-
批准号:81802809
-
项目类别:青年科学基金项目
-
资助金额:21.0万元
-
批准年份:2018
-
负责人:蔡梅春
-
依托单位:
运用ATAC-seq技术分析染色质可接近性对犏牛初级精母细胞基因表达的调控作用
-
批准号:31802046
-
项目类别:青年科学基金项目
-
资助金额:27.0万元
-
批准年份:2018
-
负责人:张龚炜
-
依托单位:
基于ATAC-seq和RNA-seq研究CWIN调控采后番茄果实耐冷性作用机制
-
批准号:31801915
-
项目类别:青年科学基金项目
-
资助金额:24.0万元
-
批准年份:2018
-
负责人:茹磊
-
依托单位:
基于ATAC-seq高精度预测染色质相互作用的新方法和基于增强现实的3D基因组数据可视化
-
批准号:31871331
-
项目类别:面上项目
-
资助金额:59.0万元
-
批准年份:2018
-
负责人:张治华
-
依托单位: