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.
身体弹性是健康衰老(竞争性更新)的预测因子

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
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
Physical performance is enhanced in old mice fed a short term diet medicated with rapamycin, acarbose, and phenylbutyrate.
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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