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

描述（由申请人提供）：人类衰老与身体和认知能力下降以及对癌症、糖尿病和神经退行性疾病的易感性显著增加有关。因此，促进健康老龄化，延长对衰退的抵抗力，是医学研究的主要目标。为了解决这个问题，简单的动物模型，如线虫C。已经对秀丽线虫进行了研究，为调节保守衰老过程的基因和药物干预提供了分子见解。这项工作的目标是参加一个合作科学小组，该小组测试药物延长健康衰老和促进C。elegans模型一个具体的重点将是测试有前途的药物对收集的自然变异的C。elegans，其将寻求代表人类群体中广泛的遗传异质性-那些在不同群体中赋予类似结果的药物将被认为在高等生物体中有效的变化增加。我们的第一个目标是对不同物种变体的衰老进行快速初步评估，使用两种快速的衰老质量检测方法来监测伴随人类衰老的保守过程：1）分析自动荧光脂褐素和晚期糖基化终产物，它们在C中积累到高水平。elegans参考菌株N2，其老化较差，但在优雅老化的动物中保持在低水平; 2）运动能力减弱，我们用强大的计算机视觉分析程序进行评估。我们将利用这些初步数据为我们的第二个目标选择一组测试菌株：在来自同一物种的不同人群中进行药物筛选，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有助于药物剂量选择和健康寿命评估。总的来说，这项拟议中的研究将明确揭示物种内的自然变异如何影响寿命和健康寿命。应确定在不同人群目标中有力促进强大健康跨度的药物干预措施。

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.