Physical resilience is a predictor of healthy aging

身体弹性是健康衰老的预测指标

基本信息

  • 批准号:
    10731992
  • 负责人:
  • 金额:
    $ 67.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-15 至 2028-04-30
  • 项目状态:
    未结题

项目摘要

Abstract Physical resilience is a predictor of healthy aging (Competitive renewal) The ability to respond to and recover from a physically stressful event is defined as physical resilience. The inherent individual variation in response to a physical stressor suggests that different stressors trigger different stress response patterns. A deeper understanding as to why some individuals maintain or regain function following an insult, while others do not, may help to characterize protective factors that can be engaged to promote resilience and healthy aging. We have developed and partially characterized three translationally relevant physical stressors in mice: acute sleep disruption (ASD), the chemotherapeutic drug cyclophosphamide (CYP), and acute cutaneous trauma (ACT), that trigger responses showing a correlation with physiological and pathological features associated with increasing age. We have shown in the first grant period that ASD, CYP, and ACT administered to middle-aged mice results in a range of responsiveness from low to high, such that mice can be categorized as resistant or susceptible and aligned with phenotypic and geropathologic parameters of aging. The hypothesis of the competitive renewal is that resilience to aging is characterized by heterogeneous response patterns unique to defined physical stressors in an age- dependent manner. Aim 1 is designed to validate physiological targets of ASD, CYP, and ACT. Responsiveness will be determined by readout assays (escape times in a learning task for ASD, neutrophil to lymphocyte ratio for CYP, and biopsy healing area for ACT) in middle aged mice as resistant or susceptible to each physical stressor. Each group of mice will then be followed to older age and aligned with phenotypic aging endpoints including assessments for memory, strength and agility. Aim 2 is designed to confirm organ- based targets of ASD, CYP, and ACT in tissues from Aim 1 mice using endpoints based on differences in geropathology lesion scores in specific organs from the two groups. Digital imaging and biostatistical paradigms for mouse PathoClock analyses will be used for evaluation of organ-specific and organ-common geropathology data. Aim 3 is designed to identify and characterize molecular pathways of ASD, CYP, and ACT in tissues from Aim 1 mice and employ RNA seq for transcriptomic pathway analysis followed by verification with nanoscale protein analytical platforms and immunohistochemistry imaging for molecular analysis of relevant pathways in stress resistant and stress susceptible mice. The data can then be aligned with data from Aims 1 and 2. Investigations into the molecular pathways utilized by cells in a particular tissue and organ in response to a physical stressor would be of merit in individuals predicted to be less resilient to aging and would have impactful significance for designing clinical studies to enhance healthy aging.
摘要身体弹性是健康老龄化的预测因子(竞争性更新) 对身体压力事件做出反应并从中恢复的能力被定义为身体弹性。的 对身体压力源的内在个体差异表明,不同的压力源触发不同的 压力反应模式更深入地了解为什么有些人保持或恢复功能 在侮辱之后,而其他人没有,可能有助于描述可以参与的保护因素, 促进恢复力和健康老龄化。我们已经开发并部分表征了三种预防性 小鼠的相关身体应激源:急性睡眠中断(ASD),化疗药物 环磷酰胺(CTX)和急性皮肤创伤(ACT),引发反应显示相关性 具有与年龄增长相关的生理和病理特征。我们在第一批补助金中 在此期间,ASD、ASD和ACT给予中年小鼠, 从低到高,使得小鼠可以被分类为抗性或易感,并与表型和 衰老的老年病理学参数竞争性更新的假设是, 其特点是在一个年龄段内,对特定的身体压力源有独特的异质反应模式- 依赖的方式。目的1旨在验证ASD、ASD和ACT的生理目标。 反应性将通过读出测定(ASD的学习任务中的逃避时间、中性粒细胞对 淋巴细胞比率(以ACT表示)和活检愈合面积(以ACT表示)作为对 每一个物理压力。然后将对每组小鼠进行随访至老年,并与表型 老化终点包括记忆力、力量和敏捷性的评估。目标2旨在确认器官- 使用基于Aim 1小鼠组织中ASD、ASD和ACT的差异的终点, 两组特定器官的老年病理学损伤评分。数字成像和生物统计学 小鼠PathoClock分析的范例将用于评价器官特异性和器官共同性 老年病理学数据。目的3旨在鉴定和表征ASD、ASD和ACT的分子途径 在来自Aim 1小鼠的组织中,并采用RNA seq进行转录组学途径分析,随后进行验证 利用纳米级蛋白质分析平台和免疫组织化学成像, 应激抵抗和应激易感小鼠中的相关通路。然后,可以将数据与来自 目标1和2。对特定组织和器官中细胞利用的分子途径的研究, 对身体压力源的反应在预测对衰老的适应力较低的个体中是有价值的, 对设计临床研究以促进健康老龄化具有重要意义。

项目成果

期刊论文数量(30)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
An immune stress test for resilience to aging: Pneumococcal vaccine response.
  • DOI:
    10.31491/apt.2020.09.035
  • 发表时间:
    2020-09-29
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Oveson R;Jiang Z;Izhaky M;Sharma K;Ladiges WC
  • 通讯作者:
    Ladiges WC
Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment.
  • DOI:
    10.31491/apt.2020.12.046
  • 发表时间:
    2020-12-31
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nickel K;Bjorner M;Ladiges W;Zhu L
  • 通讯作者:
    Zhu L
Physical performance is enhanced in old mice fed a short term diet medicated with rapamycin, acarbose, and phenylbutyrate.
The potential of GHK as an anti-aging peptide.
  • DOI:
    10.31491/apt.2020.03.014
  • 发表时间:
    2020-03-27
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Dou Y;Lee A;Zhu L;Morton J;Ladiges W
  • 通讯作者:
    Ladiges W
Wheel running predicts resilience to tumors in old mice.
轮子运转预测老年小鼠对肿瘤的恢复能力。
  • DOI:
    10.1080/20010001.2019.1676104
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Zhu,Lida;Wang,Juan;Pettan-Brewer,Christina;Ladiges,Warren;Goh,Jorming
  • 通讯作者:
    Goh,Jorming
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Warren C LADIGES其他文献

Warren C LADIGES的其他文献

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{{ truncateString('Warren C LADIGES', 18)}}的其他基金

Physical resilience is a predictor of healthy aging in mice
身体恢复能力是小鼠健康衰老的预测因素
  • 批准号:
    9418968
  • 财政年份:
    2017
  • 资助金额:
    $ 67.3万
  • 项目类别:
Physical resilience is a predictor of healthy aging in mice
身体恢复能力是小鼠健康衰老的预测因素
  • 批准号:
    10166752
  • 财政年份:
    2017
  • 资助金额:
    $ 67.3万
  • 项目类别:
Pathology of Aging Research Network
衰老病理学研究网络
  • 批准号:
    9063461
  • 财政年份:
    2014
  • 资助金额:
    $ 67.3万
  • 项目类别:
Pathology of Aging Research Network
衰老病理学研究网络
  • 批准号:
    8665573
  • 财政年份:
    2014
  • 资助金额:
    $ 67.3万
  • 项目类别:
Pathology of Aging Research Network
衰老病理学研究网络
  • 批准号:
    8846003
  • 财政年份:
    2014
  • 资助金额:
    $ 67.3万
  • 项目类别:
Mitochondrial catalase as a treatment for metastatic breast cancer
线粒体过氧化氢酶治疗转移性乳腺癌
  • 批准号:
    7707170
  • 财政年份:
    2009
  • 资助金额:
    $ 67.3万
  • 项目类别:
Cancer susceptibility of XRCC1 mutant mice
XRCC1突变小鼠的癌症易感性
  • 批准号:
    7439285
  • 财政年份:
    2008
  • 资助金额:
    $ 67.3万
  • 项目类别:
Cancer susceptibility of XRCC1 mutant mice
XRCC1突变小鼠的癌症易感性
  • 批准号:
    7609207
  • 财政年份:
    2008
  • 资助金额:
    $ 67.3万
  • 项目类别:
CORE--Transgenic Animal Support
核心——转基因动物支持
  • 批准号:
    6880488
  • 财政年份:
    2005
  • 资助金额:
    $ 67.3万
  • 项目类别:
Alzheimer's Disease and Impaired APP Proteolysis
阿尔茨海默病和 APP 蛋白水解受损
  • 批准号:
    7140287
  • 财政年份:
    2005
  • 资助金额:
    $ 67.3万
  • 项目类别:

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