权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Primary fibroblast resiliency as a predictor of health and lifespan in mice

原代成纤维细胞弹性作为小鼠健康和寿命的预测因子

基本信息

批准号：
9422077
负责人：
Adam Salmon
金额：
$ 30.94万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
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 2022-05-31
项目状态：
已结题

项目摘要

In response to RFA-AG-17-040, “Short-term Measurements of Physical Resilience as a Predictor of Healthspan in Mice”, we propose testing primary fibroblast resilience with a panel of different cellular insults as a means to predict individual mouse longevity and healthspan. As outlined by the funding announcement for this RFA, there is a need to develop these standardized tests for use among the aging community to accelerate research towards revealing mechanisms that underly the physiological decline of aging. We previously have shown that primary fibroblasts isolated from the tail skin of mice likely retain characteristics of the in vivo environment of the mouse (or other species) from which they were established. For example, we showed in a series of studies that skin- derived primary fibroblasts isolated from long-lived mice with deficiencies in growth hormone/insulin- like growth factor 1 levels are resilient to multiple cytotoxic and metabolic insults. These differences persist even after numerous population doublings in culture using identical conditions as fibroblast lines from control mice. In addition, we have shown in this fibroblast model that resiliency to one form of insult predicts resiliency to multiple other forms of insult in an individual cell line. Our overall hypothesis is that cellular resiliency of skin-derived primary fibroblasts represents the vitality of an individual in vivo and predicts both healthspan and longevity of individual mice. We have designed this study to test this hypothesis and meet the goals outlined by this RFA. In our first aim, we test whether fibroblast resiliency is predictive of individual longevity and healthspan in a normally aging group of genetically heterogeneous mice. Because of the unique fibroblast resiliency panel of tests we have outlined, we can test physical resiliency of mice with little to no effect on the overall health and longevity of the animals. That is, in an individual mouse we will measure fibroblast resilience (including repeated assessments throughout middle age) and longevity and use these data to develop a predictive model. In our second aim, we test the effect on fibroblast resiliency of interventions in mice known to alter longevity and/or healthspan. This will test whether this model can predict novel interventions that may alter these parameters within a population. Because we currently lack standardized research tools to probe resiliencies at the cellular level, this marker of resilience has the potential to be a highly important marker of healthspan and longevity in mouse studies.

为了回应RFA-AG-17-040，“身体弹性的短期测量作为一种