寿命与健康寿命的调控机制并不完全相同。虽然人们对于寿命的调控机制有了一定的了解，然而有关减缓病理性衰老的发生和行为退化的研究相对较少。申请人前期初步研究的结果显示不同品系野生型线虫的衰老速度存在明显差异，存在健康长寿的线虫品系。本项目将选取健康长寿线虫品系作为研究对象，利用数量性状基因座（QTL）或集团分离分析法（BSA），探究个体间病理性衰老速度差异的调控基因并分析单核苷酸多态性（SNP）对相关性状的影响；通过验证上述基因对行为退化和寿命的调控作用，探讨是否存在可减缓行为退化和病理性衰老的发生，并同时延长寿命的基因；阐明上述衰老病理特征调控基因促进健康长寿的作用机制。本项目从病理性衰老、行为功能退化、寿命等多个角度出发探讨个体间衰老速度差异的遗传基础，揭示可能存在同时调控寿命与健康寿命的分子途径。本项目的顺利实施将有助于阐明健康长寿的分子遗传基础，为理解衰老的生物学本质提供重要线索。

Recent studies have demonstrated that lifespan and healthspan could be separated, suggesting that their regulatory mechanisms are different. Over the past few decades, major advances have been made in terms of identifying genes and pathways that affect lifespan, but less known in molecular mechanisms of aging-related pathologies and behavioral degradation. The preliminary results of the applicant's early study showed that there are significant differences in the aging rate among wild-type C. elegans strains, and some individuals with longer lifespans could survive with low morbidity throughout life. In this project we aim to identify genes that regulate aging rate using quantitative trait loci (QTL) or bulk segregant analysis (BSA), and analyse the effects of single nucleotide polymorphisms (SNPs) on the phenotype. We will explore whether there are genes that can promote healthy aging and longevity by analysing the effects of selected genes on age-related behavioral decline and lifespan. This will be followed by understanding exactly how the genes are working to regulate both lifespan and the healthspan. This project makes full use of the advantages of C. elegans as a model organism for aging research to study the molecular mechanisms of variation in aging pathologies, age-related behavioral degradation and lifespan. Results of this study will help us to have a better understanding of genetic basis of healthy aging and longevity, and provide important clues for understanding the causes of aging.