GSE131754
RNA sequencing of mouse hepatic response to lifespan-extending interventions
This dataset consists of hepatic gene expression profiles of mice subjected to 8 different lifespan-extending interventions, together with the corresponding age-, sex- and strain-matched littermate controls: caloric restriction (CR), methionine restriction (MR), growth hormone receptor knockout (GHRKO), Snell dwarf mice (Pit1 -/-), rapamycin, acarbose, 17-alpha-estradiol (17aE2) and Protandim. Both sexes and different age groups are presented within dataset. Using this data, we identified general and specific gene expression patterns associated with lifespan extension. We detected a feminization effect associated with growth hormone regulation and diminution of sex-related differences in response to many interventions at transcriptome and metabolome levels. Combining the dataset with publicly available resources, we found that many interventions exhibited similar transcriptome changes, whereas some, including rapamycin, showed distinct patterns. We identified common hepatic signatures of lifespan extension, e.g. upregulation of oxidative phosphorylation and NRF2-regulated enzymes, and found that many perturbed pathways are shared across tissues. Moreover, the response of genes related to glucose metabolism and immune function represented both qualitative and quantitative associations with longevity. Finally, we used the detected longevity signatures to identify new candidates for lifespan extension and built GENtervention, a tool that visualizes associations of gene expression responses with lifespan extension. Overall design: 6-month-old UM-HET3 male and female mice from University of Michigan Medical School subjected to acarbose (1000 ppm), CR (40%), rapamycin (42 ppm), 17aE2 (14.4 ppm) and Protandim (1200 ppm) for 2 months, together with their littermate controls, were used for the analysis. Acarbose (1000 ppm), CR (40%) and rapamycin (14 ppm) were also analyzed for 12-month-old mice (subjected for 8 months) of the same strain. In case of MR, 2-month-old C57BL/6J male mice were subjected to diet containing 0.12% w/w methionine for 12 months and utilized together with their littermate controls subjected to the same diet but with 0.86% w/w methionine. In case of GHRKO and Snell dwarf mice, 5-month-old male mutants and their age- and sex-matched littermate controls were obtained from (C57BL/6J x BALB/cByJ)/F2 and (PW/J x C3H/HeJ)/F2 strains, respectively. 3 biological replicates were used for each experimental group, including both treated and control mice (78 samples in total). In all cases, interventions continued until the animals were sacrificed. RNA was extracted from liver tissues with PureLink RNA Mini Kit as described in the protocol and passed to paired-end sequencing with 100 bp read length.