Reduced Expression of the Proto-oncogene Myc Increases Mouse Longevity and Enhances Healthspan

MYC is a pleiotropic transcription factor that regulates numerous pathways and whose deregulation promotes cancer. Myc+/- mice have extended lifespan relative to their wild type littermates. To better understand the effects of the Myc+/- genotype on cellular processes, microarrays were performed on young (5 month) and old (24 month) Myc+/- and WT males in liver, skeletal muscle, and adipose tissues. Microarray data were used to compare the effects of aging with the effects of the Myc+/- genotype at each age, to identify pathways enriched for differentially expressed genes, and to compare the Myc+/- gene expression signature with that from other long-lived mice. Male mice of each genotype (Myc+/- and wild type) were sacrificed at 5 months and 24 months of age, and tissues were harvested and snap frozen in liquid nitrogen. RNA was extracted, and pooled between 5-8 mice within each cohort, creating one pooled sample for each combination of age, genotype, and tissue. Three technical replicates were run for each sample.MYC是一种多效转录因子，可调控多条信号通路，其表达失调可促进癌症发生。Myc+/-杂合小鼠相较于其野生型同窝仔鼠，寿命更长。 为深入解析Myc+/-基因型对细胞过程的影响，研究人员针对5月龄（青年）与24月龄（老年）的Myc+/-及野生型（wild type，WT）雄性小鼠的肝脏、骨骼肌和脂肪组织开展了微阵列（microarray）分析。 微阵列数据被用于三项核心分析：其一，在各年龄阶段分别比较衰老与Myc+/-基因型的生物学效应；其二，鉴定富集差异表达基因的信号通路；其三，将Myc+/-小鼠的基因表达特征与其他长寿小鼠的表达特征进行比对。 研究人员分别于5月龄和24月龄处死各基因型（Myc+/-与野生型）的雄性小鼠，采集组织后立即置于液氮中快速冷冻。 提取总RNA后，将每个队列中5~8只小鼠的RNA进行混合，针对年龄、基因型与组织的每一种组合制备一份混合样本。每个样本均设置三次技术重复实验。