在本组长年进行的脂代谢平衡与长寿、认知相关基因研究基础上，提出假设:体内脂代谢平衡的维持，促进了认知功能的正常，从而延缓衰老的根基是存在有编码这一连锁性状的共有核心基因群。为检验该原创性思路，拟首先根据Horvath时钟检测，过滤掉假阳性年龄个体,得出研究对象的真实生物学年龄并分组。据此，以脂代谢平衡调节基因的98个长寿关联遗传变异位点为靶，进行长寿-对照的比较基因组学研究，经高通量测序分型识别共有基因变异；经白细胞转录组表达谱及血清脂代谢指标水平、认知功能和长寿表型进行共有基因变异验证；再经生物信息学对共有基因进行功能预测；并利用体内、外模型探索共有基因变异影响寿命的分子机制。通过检测和比较长寿和当地自然衰老个体获得共有基因变异与长寿特征关联的生理和生化证据，最终通过人群、体内、外模型和分子水平研究综合分析，初步解释脂代谢稳态维持正常认知功能进而延缓衰老的遗传和分子机制。

Base on lipid metabolism balance and longevity and cognitive-related genes in our group with the long-term researches, we hypothesize that there is a sharing core gene group which link traits to maintain the balance of lipid metabolism, then to promote the normal function of cognitive function in brain, thus to delay the foundation of aging in the body. In order to verify the original idea, we propose to filter out the false positive age of individuals according to Horvath clock correction, in contrast chronology years old, and obtain the true biological age of the subjects and group them firstly. Second, we choose 98 longevity related genetic variation loci of lipid metabolism balance regulatory genes as candidate target to study more than 8,000 longevity-control comparative genomics. Sharing gene variations of lipid metabolism and longevity and cognition can be identified by high-throughput sequencing. Third, we perform sharing gene mutations validation by leukocyte transcriptome and a level of serum lipid metabolism, cognitive function and longevity phenotype. Fourth, we use bioinformatics for functional prediction of sharing genes. Fifth, we explore the molecular mechanism of lipid metabolism and longevity and cognitive consensus gene mutations affecting lifespan by models in vivo and vitro. Finally, through detecting and comparing the physiological and biochemical evidences of longevity characteristics and the consensus gene mutations between longevity and age control group out of local natural aging individuals, we are going to preliminarily interpret the genetic and molecular mechanisms which lipid homeostasis can maintain normal cognitive function, in turn, delay aging by the comprehensive analysis of population, in vivo and vitro models, molecular level studies.