Project description:The aim of the current work was to evaluate the ovarian transcriptome in Ames dwarf (df/df) mice. df/df mice have a delayed ovarian aging compared to normal (N) mice. Although a high number of genes were differentially expressed during aging of N mice, only a small fraction of these changed with aging in df/df mice. These alterations involved more than 500 categorized biological processes. The majority of these biological processes, including inflammatory/immune responses, were up-regulated with aging in N mice, while old df/df mice were characterized by down-regulation of these same processes in comparison to age matched N mice. However, biological processes related to DNA damage and repairing were commonly down-regulated with aging in both genotypes. In conclusion, delayed ovarian aging in long-living df/df mice was associated with reduced expression of genes related to the inflammatory and immune responses.
Project description:Recent evidence demonstrates that serum levels of specific small noncoding RNAs (sncRNAs) including miRNAs and 5’ tRNA halves significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long-lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype-specific changes in the circulating levels of 43 miRNAs and 19 5’ tRNA halves during aging [Genotype-by-Age interaction (GbA)]. GbA miRNAs showed four distinct expression patterns and significant over-targeting of transcripts involved in age-related processes. Functional enrichment analysis of putative miRNA targets highlighted cellular processes such as tumor suppression, anti-inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long-lived mouse suggests CR-like and CR-independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs and 5’-tRNA halves modulated by age in the long-lived Ames mouse.
Project description:Female Ames dwarf mouse (df/df) with ad libitum access to water and standard pelleted food (LabDiet, PMI Feeds, Inc., St Louis, MO) caged with microisolator filter tops. Mice were killed between 24 to 26 months of age, tissues removed, rapidly frozen on dry ice, and stored in liquid nitrogen. Total liver RNA was isolated from frozen tissue as described (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). mRNA levels were measured using the Affymetrix mouse U74Av2 array according to standard protocols. After hybridization, arrays were scanned using a Hewlett-Packard GeneArray Scanner. Image analysis was performed as described (Cao SX, Dhahbi JM, Mote PL, and Spindler SR. Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice. Proc Natl Acad Sci U S A 98: 10630-10635, 2001). A more detailed description of the methods can be found in (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). Keywords = Ames dwarf Keywords = mouse Keywords = Affymetrix Keywords = caloric restriction Keywords: parallel sample
Project description:To compare and contrast genetic signatures from livers of young and aged Ames dwarf mice with their wild type controls. SUBMITTER_CITATION: W. H. Boylston, James H. DeFord, John Papaconstantinou (2006) Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice Age 28:125-144 Experiment Overall Design: 25 micrograms of liver RNA was isolated from young (5 dwarfs, 5 wildtype), middle aged (5 dwarfs, 5 wild type) and aged (5 dwarf, 6 wild type) mice for use in hybridization of Affymetrix gene chips according to Affymetrix protocols.
Project description:Female Ames dwarf mouse (df/df) with ad libitum access to water and fed 30% less of the standard pelleted diet with respect to the amount consumed by female ad libitum fed df/df mice (LabDiet, PMI Feeds, Inc., St Louis, MO) caged with microisolator filter tops. Mice were killed between 24 to 26 months of age, tissues removed, rapidly frozen on dry ice, and stored in liquid nitrogen. Total liver RNA was isolated from frozen tissue as described (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). mRNA levels were measured using the Affymetrix mouse U74Av2 array according to standard protocols. After hybridization, arrays were scanned using a Hewlett-Packard GeneArray Scanner. Image analysis was performed as described (Cao SX, Dhahbi JM, Mote PL, and Spindler SR. Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice. Proc Natl Acad Sci U S A 98: 10630-10635, 2001). A more detailed description of the methods can be found in (T. Tsuchiya, J.M. Dhahbi, X. Cui, P.L. Mote, A. Bartke, S.R. Spindler, Physiological Genomics, Submitted). Keywords = Ames dwarf Keywords = mouse Keywords = Affymetrix Keywords = caloric restriction Keywords: parallel sample
Project description:Ovarian tissue was collected at 5-6 months and at 21-22 months of age for miRNA sequencing. We detected a total of 404 miRNAs in the ovarian samples, from which the abundance of 22 and 33 miRNAs changed with age in N and df/df mice, respectively. Of these, only three miRNAs were commonly regulated with age between N and df/df mice, indicating a very divergent miRNA profile between genotypes. We also detected that 46 miRNAs were regulated between N and df/df mice, of which 23 were regulated exclusively in young mice, 12 exclusively in old mice and 12 commonly regulated at young and old ages. Many genes likely to be targeted by these miRNAs are involved in the FoxO, mTOR, PI3k/Akt and insulin signaling pathways. These results suggest that the aging process has a differential impact on the ovarian miRNA profile in df/df mice, and suggest that these miRNAs can be central players in the maintenance of a younger ovarian phenotype.
Project description:To compare and contrast genetic signatures from livers of young and aged Ames dwarf mice with their wild type controls. Keywords: Time Course
Project description:To compare and contrast genetic signatures from livers of young and aged Snell dwarf mice with their wild type controls. SUBMITTER_CITATION: W. H. Boylston, James H. DeFord, John Papaconstantinou (2006) Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice Age 28:125-144 Experiment Overall Design: 25 micrograms of liver RNA was isolated from each of 6 aged (3 dwarf, 3 wild type) and 8 young (4 dwarf, 4 wild type) mice for use in hybridization of Affymetrix gene chips according to Affymetrix protocols.