Mechanisms of Life Span Extension and Rejuvenation By Adult Reproductive Diapause

成人生殖滞育延长寿命和恢复活力的机制

基本信息

批准号：
8961538
负责人：
MATT KAEBERLEIN
金额：
$ 33.22万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-15 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8961538
关键词：
Adult Age Aging Aging-Related Process Animals Appearance Bacteria Biological Biological Aging Biological Models Biological Preservation Caenorhabditis elegans Cell Aging Cell Maintenance Cell Nucleus Cells Characteristics Chromosomes Data Diapause Disease Faculty Fluorescence Microscopy Food Freezing Genes Genetic Germ Cells Goals Gonadal structure Homologous Gene Hour Human Intervention Laboratories Lead Longevity Maintenance Measures Mediating Microscope Mitochondria Modeling Molecular Movement Muscle Mutation Natural regeneration Nematoda Oocytes Organelles PTEN gene Pathology Pathway interactions Phenotype Population Positioning Attribute Process Property RNA Interference Recovery Rejuvenation Reporter Reporting Reproductive system Research Resolution Role Signal Transduction Somatic Cell Source Starvation Stem cells Structure Symptoms Temperature Testing Tissues Toxic effect Transmission Electron Microscopy Universities Washington age effect age related aged arm catalyst cell age cell motility deprivation feeding genome-wide genome-wide analysis germline stem cells healthy aging insight notch protein novel novel strategies offspring polyglutamine prevent public health relevance reproductive research study stem cell niche

项目摘要

DESCRIPTION (provided by applicant): The majority of gerontological research is focused on understanding biological mechanisms of aging, with a primary goal to develop interventions that slow the aging process in order to enhance healthspan and lifespan. While this approach has proven quite successful in laboratory models, an alternative, and potentially much more powerful strategy, is to focus on interventions that promote rejuvenation of aged cells or animals toward a more youthful state. Mechanisms of rejuvenation have been understudied, however, largely because of the lack of robust and tractable biological models. We believe that we have overcome this barrier by developing a model for rejuvenation of aged somatic cells and regeneration of a youthful reproductive system in the nematode Caenorhabditis elegans. Adult reproductive diapause can be induced by removing the bacterial food source from C. elegans at the transition from L4 to adulthood. ARD animals survive at least 3-fold longer than normal adult C. elegans, but still age as indicated by morphological and structural changes to organelles, cells, and tissues. Upon exit from ARD, these aged animals show a remarkable rejuvenation of both reproductive and somatic tissues that we hypothesize is mediated by protected germline stem cells. Rejuvenated animals go on to have a full lifespan as if they were day 1 adults. The goal of this proposal is to understand the mechanisms underlying this rejuvenation process, in particular the signals emanating from the protected germline stem cells to restore somatic tissues to their youthful state. Understanding and harnessing these mechanisms will lead to novel strategies to restore aged tissues to a more youthful state in people, thereby promoting healthy aging by preventing age- related pathology that drives disease.

描述（由申请人提供）：大多数老年学研究的重点是了解衰老的生物学机制，其主要目标是开发减缓衰老过程的干预措施，以延长健康寿命和寿命，而这种方法已在实验室中证明相当成功。模型，另一种可能更强大的策略是专注于促进衰老细胞或动物恢复年轻状态的干预措施，但是，在很大程度上，恢复机制尚未得到充分研究。由于缺乏强大且易于处理的生物学模型，我们相信，通过开发一种模型，可以通过消除线虫成年体细胞的再生和年轻生殖系统的再生来克服这一障碍。从 L4 到成年的过渡阶段，来自线虫的细菌食物来源的存活时间至少是正常成年线虫的 3 倍，但仍如所示的那样老化。通过细胞器、细胞和组织的形态和结构变化，这些衰老的动物在受保护的生殖干细胞的介导下表现出生殖和体细胞组织的显着恢复。该提案的目的是了解这一再生过程的机制，特别是受保护的生殖干细胞发出的信号，使体细胞恢复年轻状态。了解和利用这些机制将带来新的策略，将人体的衰老组织恢复到更年轻的状态，从而通过预防导致疾病的年龄相关病理来促进健康老龄化。