mouse methylation-12v1-0 beadchip array  (INFINIUM Inc)

Journal: bioRxiv

Article Title: Functional and multi-omic aging rejuvenation with GLP-1R agonism

doi: 10.1101/2024.05.06.592653

Figure Lengend Snippet: a , Scatter plots showing DNA methylation level changes in aging ( x -axis) vs. exenatide treatment ( y -axis) in sites covered by the Illumina mouse 285k array (mm285k) across different tissue organs and circulating white blood cells (WBCs). Each dot represents one differentially methylated locus (DML), color-coded by treatment (Rx) effect categories as shown in the inset (rejuvenation: opposing aging and Rx effects; exacerbation: same aging and Rx effects; aging- or Rx-dominant: statistically significant in the respective comparison only; no additional label: significant for both aging and Rx effect comparisons, also see Methods ). For each plot, the line represents linear fit. The Spearman correlation coefficients ( R S ) and associated P -values are also shown. Inset of left upper panel: symbol for DNA methylation. b , Summary bar plot of the proportions of DML among the mm285k array sites under different categories (as specified in the inset of a ). c , Similar to b , but for DML among the imputed mammalian conserved sites covered by the mammalian 40k array (mm40k). Sample sizes for the various tissue organs (young adult vehicle, aged vehicle, aged exenatide): hypothalamus (4, 4, 5), frontal cortex (8, 8, 8), hippocampus (8, 8, 8), adipose tissue (8, 8, 8), liver (8, 8, 8), circulating WBCs (5, 9, 6), heart (8, 8, 8), kidney (7, 9, 8), skeletal muscle (8, 8, 8), colon (7, 9, 8), spleen (8, 8, 8).

Article Snippet: DNA methylation assays were carried out by the Clock Foundation using a custom BeadChip array containing loci from the Infinium Mouse Methylation BeadChip (i.e., mm285k array ) and the mammalian methylation array (i.e., mm40k array ).

Techniques: DNA Methylation Assay, Methylation, Comparison

Journal: bioRxiv

Article Title: Functional and multi-omic aging rejuvenation with GLP-1R agonism

doi: 10.1101/2024.05.06.592653

Figure Lengend Snippet: a , Schematic of experimental design for the aged short-term treatment cohort. The animals either received hypothalamic injection of adeno-associated virus vector (AAV) for the expression of shRNA to knockdown Glp1r or scramble shRNA, and either received vehicle, exenatide, or rapamycin treatment. Abbreviations: HTH, hypothalamus. KD, knockdown. OGTT: oral glucose tolerance test. b , Mean (±S.D.) hypothalamic Glp1r transcript expression levels measured with quantitative PCR ( n = 3 mice from each group used for the comparison), relative to the mean of aged control group (i.e., hypothalamic scramble shRNA-AAV injection, treated with vehicle). c , Scatter plots showing transcriptomic changes in aging ( x -axis) vs. exenatide treatment ( y -axis) in different tissue organs and circulating white blood cells (WBCs). Each dot represents one differentially expressed gene (DEG), color-coded by treatment (Rx) effect categories as shown in the inset (rejuvenation: opposing aging and Rx effects; exacerbation: same aging and Rx effects; aging- or Rx-dominant: statistically significant in the respective comparison only; no additional label: significant for both aging and Rx effect comparisons, also see Methods ). Inset of left panel: symbol for transcript. d , Summary bar plot of the proportions of DEGs under different categories (as specified in the inset of c ). e and f , Similar to c and d , but for showing exenatide treatment effects in aged animals with hypothalamic Glp1r knockdown. g , Scatter plots showing DNA methylation level changes in aging ( x -axis) vs. exenatide treatment ( y -axis) in sites covered by the Illumina mouse 285k array (mm285k) across different tissue organs and circulating WBCs. Each dot represents one differentially methylated locus (DML), color-coded by treatment (Rx) effect categories (as shown in the inset of c ). Inset of left panel: symbol for DNA methylation. h , Similar to g , but for showing exenatide treatment effects in aged animals with hypothalamic Glp1r knockdown. i , Scatter plot showing plasma metabolomic changes in aging ( x -axis) vs. exenatide treatment ( y -axis). Each dot represents one metabolite. j , Similar to i , but for showing exenatide treatment effects in aged animals with hypothalamic Glp1r knockdown. In c , e , and g – j , the lines represent linear fits (with confidence interval (grey) in i and j ). The Spearman correlation coefficients ( R S ) and associated P -values are also shown. Sample sizes for data in c – j : n = 5 mice for each experimental group for the various tissues, except n = 4 aged exenatide-treated mice (src group) for circulating WBCs transcriptomic profiling.

Article Snippet: DNA methylation assays were carried out by the Clock Foundation using a custom BeadChip array containing loci from the Infinium Mouse Methylation BeadChip (i.e., mm285k array ) and the mammalian methylation array (i.e., mm40k array ).

Techniques: Injection, Virus, Plasmid Preparation, Expressing, shRNA, Real-time Polymerase Chain Reaction, Comparison, DNA Methylation Assay, Methylation

Journal: bioRxiv

Article Title: Functional and multi-omic aging rejuvenation with GLP-1R agonism

doi: 10.1101/2024.05.06.592653

Figure Lengend Snippet: a , Longitudinal changes in average daily food intake per mouse for animals in the different experimental groups (monitored weekly). Abbreviations: scr, scramble shRNA group; KD, knockdown group. b , Mean (±S.D.) body weight of the animal groups throughout the treatment period (monitored weekly). c , Oral glucose tolerance test (OGTT) results for the different experimental groups at the end of 13-week treatment (Rx) period. P -value: one-way ANOVA with Holm-Sidak’s post-hoc multiple comparisons test for area under the curve (AUC). d , Gonadal fat weight as percentage of body weight in the different experimental groups. P -value: one-way ANOVA with Tukey’s post-hoc test for multiple comparisons. e , Scatter plots showing transcriptomic changes with exenatide treatment in aged control (scramble shRNA) mice ( x -axis) vs. hypothalamic (HTH) Glp1r knockdown ( y -axis) mice across the different tissue organs and circulating white blood cells (WBCs). Each dot represents one differentially expressed gene (DEG), color-coded by treatment (Rx) effect categories as shown in the inset (same or opposite Rx effects; dominant in scr or KD: statistically significant in the respective comparison only; no additional label: significant for both comparisons, also see Methods ). Inset of left panel: symbol for transcript. f , Similar to e , but showing the results for exenatide treatment-induced differentially methylated loci (DML) covered by the Illumina mouse 285k array (mm285k) across different tissue organs and circulating WBCs. Inset of left panel: symbol for DNA methylation. g , Scatter plot showing plasma metabolomic changes with exenatide treatment in aged control (scramble shRNA) mice ( x -axis) vs. HTH Glp1r knockdown ( y -axis) mice. For each plot in e – g , the line represents linear fit (with confidence interval (grey) in g ). The Spearman correlation coefficients ( R S ) and associated P -values are also shown. Sample sizes for data in all plots: n = 5 mice for each experimental group for the various tissues, except n = 4 aged exenatide-treated mice for circulating WBCs transcriptomic profiling.

Article Snippet: DNA methylation assays were carried out by the Clock Foundation using a custom BeadChip array containing loci from the Infinium Mouse Methylation BeadChip (i.e., mm285k array ) and the mammalian methylation array (i.e., mm40k array ).

Techniques: shRNA, Comparison, Methylation, DNA Methylation Assay

Journal: bioRxiv

Article Title: Functional and multi-omic aging rejuvenation with GLP-1R agonism

doi: 10.1101/2024.05.06.592653

Figure Lengend Snippet: a , Scatter plots showing transcriptomic changes in aging ( x -axis) vs. rapamycin treatment ( y -axis) in different tissue organs and circulating white blood cells (WBCs). Each dot represents one differentially expressed gene (DEG), color-coded by treatment (Rx) effect categories as shown in the inset (rejuvenation: opposing aging and Rx effects; exacerbation: same aging and Rx effects; aging- or Rx-dominant: statistically significant in the respective comparison only; no additional label: significant for both aging and Rx effect comparisons, also see Methods ). Inset of left panel: symbol for transcript. b , Summary bar plot of the proportions of differentially expressed genes (DEGs) under different categories (as specified in the inset of a ). c , Scatter plots showing DNA methylation level changes in aging ( x -axis) vs. exenatide treatment ( y -axis) in sites covered by the Illumina mouse 285k array (mm285k) across different tissue organs and circulating WBCs. Each dot represents one differentially methylated locus (DML), color-coded by treatment Rx effect categories (as shown in the inset of a ). Inset of left panel: symbol for DNA methylation. d , Scatter plot showing plasma metabolomic changes in aging ( x -axis) vs. rapamycin treatment ( y -axis). Each dot represents one metabolite. e , f , and g , Scatter plots showing transcriptomic ( e ), DNA methylation level ( f ), and plasma metabolomic ( g ) changes with rapamycin ( x -axis) vs. exenatide ( y -axis) treatment. Inset of e , DEG and DML categories, indicating: same or opposite Rx effects; GLP-1RA- or mTORi-dominant: statistically significant in the respective comparison only; no additional label: significant for both Rx effect comparisons (also see Methods ). Inset of left panels of e and f : symbols for transcript and DNA methylation, respectively. In a , c – g , the lines represent linear fits (with confidence interval (grey) in d and g ). The Spearman correlation coefficients ( R S ) and associated P -values are also shown. h , Heatmap showing the normalized expression (Norm. exp.) levels of significant differentially expressed gene modules with exenatide and/or rapamycin treatment. Inset (left) shows the color coding for tissue origin and Rx effect category (i.e., significant with exenatide, rapamycin, or both treatments). i , Bubble chart showing the gene ontology–biological process (GO:BP) pathways with significant enrichment among the different treatment-upregulated gene modules with exenatide and/or rapamycin treatment (top 3 for each tissue organ/circulating WBCs plotted). Gene count is represented with bubble size. Tissue origin and Rx effect category are color-coded as per the inset. j , Similar to i , but for treatment-downregulated gene modules. Sample sizes for all plots: n = 5 mice for each experimental group for the various tissues, except n = 4 aged exenatide- and 4 rapamycin-treated mice for circulating WBCs transcriptomic profiling.

Article Snippet: DNA methylation assays were carried out by the Clock Foundation using a custom BeadChip array containing loci from the Infinium Mouse Methylation BeadChip (i.e., mm285k array ) and the mammalian methylation array (i.e., mm40k array ).

Techniques: Comparison, DNA Methylation Assay, Methylation, Expressing