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，延长抗衰退能力，是医学研究的一个主要目标。为了解决这个问题，简单的动物模型，如线虫秀丽隐杆线虫已经被研究，提供了分子洞察基因和药物干预，调节保守老化过程。这项工作的目标是参与一个合作科学小组，在秀丽隐杆线虫模型中测试药物延长健康衰老和促进寿命的能力。一个特别的重点将是在一组秀丽隐杆线虫的自然变体上测试有希望的药物，这将寻求代表人类群体中广泛的遗传异质性——那些在不同人群中赋予相似结果的药物将被认为在高等生物中具有更大的有效性变化。我们的第一个目标是对不同物种的衰老进行快速的初步评估，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，它们在秀丽隐杆线虫参考菌株N2中积累到高水平，而在衰老缓慢的动物中保持低水平；2)运动能力下降，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：在同一物种的不同种群中进行药物筛选，以促进长寿和健康。我们在制定快速评估健康跨度措施方面的专业知识应有助于药物剂量选择和健康跨度评估。总的来说，这项提议的研究将明确地揭示物种内部的自然变异如何影响寿命和健康寿命。应该确定在不同人群目标中强有力地促进健康的药物干预措施。

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.