short-term calorie restriction in male mice feminizes gene expression and alters key regulators of conserved aging regulatory pathways短期卡路里限制在雄性小鼠雌性化基因表达和改变守恒的老化管理途径的主要监管机构.pdfVIP

Short-Term Calorie Restriction in Male Mice Feminizes Gene Expression and Alters Key Regulators of Conserved Aging Regulatory Pathways 1 2 2,3,4 Preston Wayne Estep, III *, Jason B. Warner , Martha L. Bulyk 1 Longenity, Inc., Lincoln, Massachusetts, United States of America, 2 Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 4 Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, Massachusetts, United States of America Abstract Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown, and the involvement of the TOR and sirtuin pathways (which regulate aging in simpler organisms) remain controversial. Additionally, females of most mammals appear to live longer than males within species; and, although it remains unclear whether this holds true for mice, the relationship between sex-biased and CR-induced gene expression remains largely unexplored. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging