Healthspan Analysis of C. elegans Strains Treated with Candidate Anti Aging Inter

描述(申请人提供)：人类衰老与身体和认知能力下降以及癌症、糖尿病和神经退行性疾病的易感性显著增加有关。因此，促进健康衰老，并延长对衰老的抵抗力，是医学研究的主要目标。为了解决这个问题，人们研究了线虫等简单的动物模型，为调节保守的衰老过程的基因和药物干预提供了分子见解。这项拟议工作的目标是参加一个合作的科学小组，该小组测试药物在线虫模型中延长健康衰老和延长寿命的能力。一个特别的重点将是在线虫的一系列自然变种上测试有希望的药物，这些变种将寻求代表人类群体中广泛的遗传异质性--那些在不同群体中产生类似结果的药物将被认为具有更大的变化，即在高等生物体中有效。我们的第一个目标是使用两种快速的老化质量分析来对不同的物种变异如何老化进行快速初步评估，这两种快速分析监测伴随人类衰老的保守过程：1)分析自动荧光脂褐素和高级糖基化最终产物，它们在线虫参考菌株N2中积累到高水平，老化较差，但在优雅老化的动物中保持在低水平；2)运动能力减弱，我们使用强大的计算机视觉分析程序进行评估。我们将使用这些初步数据来选择一组测试菌株，以实现我们的第二个目标：从同一物种的不同人群中筛选药物，以促进长寿和健康。我们在开发快速评估健康寿命措施方面的专业知识应该有助于药物剂量选择和健康寿命评估。总体而言，这项拟议的研究将明确地揭示物种内的自然变异如何影响寿命和健康寿命。应该确定在不同的人群目标中强有力地促进健康的药理干预措施。

DESCRIPTION (provided by applicant): Human aging is associated with physical and cognitive decline as well as a marked increase of susceptibility to cancer, diabetes, and neurodegenerative disease. As such, the promotion of healthy aging, with extended resistance to decline, is a major goal of medical research. To address this problem, simple animals models such as the nematode C. elegans have been studied, providing molecular insights into the genes and drug interventions that modulate conserved aging processes. The goal of the proposed work is to participate in a co-operative scientific group that tests drugs for the abilityto extend healthy aging and promote longevity in the C. elegans model. A specific emphasis will be to test promising drugs on a collection of natural variants of C. elegans, which will seek to represent the extensive genetic heterogeneity in the human population-those drugs that confer similar outcomes across a diverse population will be considered to have an increased change of being efficacious in higher organisms. Our first goal is to conduct a fast preliminary evaluation o how diverse species variants age, using two fast assays of aging quality that monitor conserved processes that accompany human aging: 1) analysis of auto fluorescent lipofuscin and advanced glycation end products, which accumulate to high levels in C. elegans reference strain N2 that age poorly but remain at low levels in animals that age gracefully; 2) diminished locomotory capacity, which we evaluate with powerful computer vision analysis programs. We will use this preliminary data to select a test set of strains for our second goal: drug screening across a diverse population from the same species for promotion of longevity and healthspan. Our expertise in developing rapidly assessed healthspan measures should facilitate drug dose selection as well as healthspan evaluation. Overall, the proposed study will definitively shed insight into how natural variation within a species impacts longevity and healthspan. Pharmacological interventions that robustly promote strong healthspan across a varied population target should be identified.