Cellular Aging in a Yeast Model System

酵母模型系统中的细胞老化

基本信息

批准号：
7392287
负责人：
S MICHAL JAZWINSKI
金额：
$ 36.17万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-05-01 至 2012-03-31
项目状态：
已结题

项目摘要

The genetic and molecular analysis of aging in model systems has made exceptional strides. Certain themes have emerged that appear to have broad applicability. In addition, the participation of mitochondria in aging has taken on new dimensions, and the realization that organelle integrity and cross-talk play a role in cellular aging, likely including stem cell aging, is becoming evident. The long-term objective of the proposed research is to exploit the yeast model system for a better understanding of these emerging insights, with the goal of ameliorating aging decline in humans. The pathway that signals mitochondrial dysfunction to the nucleus, called the retrograde response, will be examined in detail in terms of its activation during normal aging. This will include an analysis of the requirements of the retrograde response genes for the maintenance of life span as cells age. The association of the main branches of the retrograde response with extended life span will be examined. The interaction between retrograde and Ras2 signaling will be dissected at the molecular level, and the signal proximal to mitochondria that triggers the retrograde response will be identified. The mechanisms underlying mitochondria-based age asymmetry between mother and daughter cells will be characterized by studying partition of newly-synthesized mitochondrial material and organelle turnover. The effects of these mechanisms on life span will be determined. The novel cross-talk between mitochondria and peroxisomes, which plays a role in age asymmetry will be examined at the molecular level, and the extent to which additional features of age asymmetry operate will be examined using a genetic approach.

模型系统中衰老的遗传和分子分析取得了非凡的进步。肯定已经出现的主题似乎具有广泛的适用性。此外，线粒体的参与衰老过程呈现出新的维度，并且认识到细胞器完整性和串扰在其中发挥着作用细胞衰老（可能包括干细胞衰老）的影响正变得越来越明显。该组织的长期目标拟议的研究是利用酵母模型系统来更好地理解这些新兴的见解，以改善人类衰老衰退为目标。线粒体信号通路细胞核功能障碍，称为逆行反应，将根据其激活进行详细检查在正常老化过程中。这将包括对逆行反应基因的需求进行分析随着细胞老化维持寿命。逆行反应主要分支的关联将检查寿命延长的情况。逆行信号和 Ras2 信号之间的相互作用将是在分子水平上进行剖析，以及触发逆行的接近线粒体的信号响应将被识别。基于线粒体的年龄不对称的机制母细胞和子细胞将通过研究新合成的线粒体的分配来表征物质和细胞器的周转。这些机制对寿命的影响将被确定。这线粒体和过氧化物酶体之间的新型串扰在年龄不对称中发挥作用在分子水平上进行检查，年龄不对称的其他特征起作用的程度将使用遗传学方法进行检查。