Rapamycin treatmented middle-aged mice
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PROVIDER: PRJEB13256 | ENA |
REPOSITORIES: ENA
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Project description:Leanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension. We show here that deficiency of the lipid synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which reduces body fat in mice, promotes longevity. Female DGAT1-deficient mice were protected from age-related increases in body fat, non-adipose tissue triglycerides, and markers of inflammation in white adipose tissue. These metabolic changes were accompanied by an increased mean and maximal lifespan of ~25% and ~10%, respectively. The gene expression profile of DGAT1-deficient mice was not highly correlated with calorie restriction of sex and age matched wild-type littermates. Our findings indicate that loss of DGAT1-mediated lipid synthesis results in leanness, protects against age-related metabolic consequences, and thus extends longevity. Liver gene expression profiles between short-term calorie restricted wild-type (WTCR) and Dgat1 deficient (KO) middle-aged (15-16 mo) female mice were compared to determine if calorie restriction and Dgat1 deficiency rely on common regulatory pathways for the promotion of longevity. Both CR and KO were compared to middle-aged wild-type female littermates fed a standard chow diet ad libitum (WTAL).
2012-02-09 | E-GEOD-26267 | biostudies-arrayexpress
Project description:The mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. We performed microarray experiment to characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR) and compare it with normal-lived control flies (C). We sampled adult females at two time points representing middle age (90% survival) and old age (10% survival) respectively, in three adult diets (malnutrition, optimal food, and overfeeding).
2012-03-31 | E-GEOD-36582 | biostudies-arrayexpress
Project description:Since healthspan-extending interventions such as caloric restriction or fasting robustly promote lipid catabolism, we investigated how lifespan and healthspan were affected by increased lipid catabolism via bmm (brummer, FBgn0036449), the major triglyceride hydrolase in Drosophila. Global overexpression of bmm strongly promoted lifespan extension as well as numerous markers of healthspan, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Increased Bmm robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER stress via improved proteostasis. Overexpression of bmm recapitulated major physiological changes associated with dietary restriction (DR) and conveyed its effects through dSir2. Taken together, these data show that bmm overexpression has broad beneficial effects on healthspan, and implicate lipolysis as a key node underlying the beneficial effects of dietary interventions known to improve healthspan.
2022-09-27 | GSE178816 | GEO
Project description:Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 signaling pathway inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprogramming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Although rapamycin showed a much more subtle effect on global translation than did caffeine, rapamycin was more effective in prolonging chronological lifespan. Rapamycin prolonged the lifespan of non-growing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.
2013-05-05 | E-MTAB-1489 | biostudies-arrayexpress
Project description:The nutrient-sensing Target of Rapamycin complex 1 (TORC1) is an evolutionarily conserved regulator of longevity. S6 kinase (S6K) is an essential downstream mediator for the effect of TORC1 on longevity. However, mechanistic insights on how TORC1-S6K signalling promotes lifespan and healthspan are still limited. Here we show that activity of S6K in the Drosophila fat body is essential for rapamycin-mediated longevity. Fat-body-specific activation of S6K blocked lifespan extension upon rapamycin feeding and induced accumulation of multilamellar lysosomal enlargements. Besides, fat body-specific S6K knockdown extended lifespan in files. We performed proteomics for Drosophila fat body to explore the fat body-specific regulation of protein expression by two separate datasets: fat body-specific S6K activation (Lsp2GS>S6KCA) with rapamycin treatment; and fat body-specific S6K inhibition (Lsp2GS>S6KRNAi). To assess if the age-prolonging mechanisms of TORC1-S6K signalling are conserved between flies and mammals, we assessed the impact of rapamycin treatment in the proteome of liver from C3B6F1 mice (F1 hybrids of C3H/HeOuJ females and C57Bl/6N males).
2024-01-12 | PXD035293 | Pride
Project description:Age-related methylation changes have been identified in various tissues and organisms, yet the underlying DNA methylation alterations in muscle aging process have not been clearly clarified. Whilst, many studies revealed that the structural and functional changes in skeletal muscle during aging process started from the mid-point of lifespan. In this study, we used pigs aged 0.5 year and 7 years, representing young and middle-aged periods. Using methylated DNA immunoprecipitation sequencing, we performed comprehensive genome-wide DNA methylation profiling for longissimus dorsi muscle in young and middle-aged pigs. We found more genes showed differently methylated in genebody. In details, 185 human ortholog genes contained DMRs that located in the promoter region, while 657 genes and 1063 genes with DMRs in gene body showed hypermethylation and hypomethylation in MA pigs, respectively. From the gene enrichment analysis, genebody hypermethylated genes showed significant enrichment for several molecular functions such as M-bM-^@M-^XGTPase regulator activityM-bM-^@M-^Y, M-bM-^@M-^XATP bindingM-bM-^@M-^Y and M-bM-^@M-^Xprotein kinase activityM-bM-^@M-^Y. Notably, genebody hypomethylated genes showed significant enrichment for various proteolysis and protein catabolic process. However, genes with DMR in their promoter region were not significantly enriched in any biology process. Proteolysis-associated genes, such as FOXO3 and FGFR1, showed different genebody methylation and mRNA expression level in two age groups, which may contribute to muscle atrophy during aging. Especially, other tumorigenesis-associated genes including GPI and GRB2, exhibited increasing mRNA level in middle-aged pigs, suggesting the possible higher risk of having cancer in human middle-aged period. Our results will serve as a valuable resource in aging studies, promote pig as a model organism for human aging research and accelerate the considerable development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference and the genome-wide gene expression profile between the two age periods. This submission represents transcriptome component of study.
2014-08-02 | E-GEOD-49791 | biostudies-arrayexpress
Project description:Many studies have addressed the effects of adult diet on gene expression in Drosophila melanogaster, however, little is known about how developmental diet influences adult gene expression, and how this interacts with adult dietary conditions. We found that developmental and adult diet exert largely independent effects on gene expression, with the effect of adult diet being considerably larger.We did find effects of developmental diet on the transcriptome that persist into middle and old-age. Most of the genes affected show no correlation with the observed phenotypic effects of larval diet on lifespan, however, in each sex we identified a cluster of ribosome, transcription, and translation-related genes whose expression was altered across the lifespan and negatively correlated with lifespan.
2017-07-27 | GSE101882 | GEO
Project description:Background: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. Results: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. Conclusions: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference between the two age periods.
2014-08-02 | E-GEOD-50716 | biostudies-arrayexpress
Project description:The thymus is primarily responsible for generating naïve, self-tolerant T cells from hematopoietic precursors. Thymic epithelial cells (TECs) together with other stromal cells create a specialized microenvironment which orchestrates the major selection processes for T cell development. Thymic function progressively deteriorates as part of the aging process, with a dramatic loss in TECs and T cell production, and this ultimately constrains the host immune repertoire. We have previously demonstrated the role of sex steroids in thymic involution in male mice, with surgical castration of middle-aged (9-12 month) male mice resulting in thymus regeneration, peaking around day 28. We have also demonstrated phenotypic alterations in TEC subsets within one week following castration that may contribute to this transient thymus regeneration effect. In this study, we aimed to examine genetic alterations in TEC and non-TEC stromal cell subsets (predominantly fibroblasts and endothelial cells) during age-related thymic involution (5-6 week old young adults compared to 9-12 month middle aged); and genetic changes in TEC and non-TEC at several timepoints following castration, to identify factors that may be involved in thymus regeneration.
2019-06-06 | GSE132278 | GEO
Project description:Analysis of function of CD11c+ cells from middle-aged and young mice at gene level. This experiment provided insight into the different genes that plays roles in inflammation, immune response and mainly arachidonic acid cascade that are differentiall expressed in CD11c+ cells from middle aged and young mice. Total RNA was isolated from pulmonary CD11c cells (separated using magnetic beads) from middle-aged and young mice
2015-08-11 | E-GEOD-71868 | biostudies-arrayexpress