Biomedical subjects

Eun-Soo Han

Publications and source records attributed to Eun-Soo Han.

6 recordsLinked to original sources

PubMed2006

Tissue specific and non-specific changes in gene expression by aging and by early stage CR.

Aging alters the expression of a variety of genes. Calorie restriction (CR), which extends life span in laboratory rodents, also changes gene expression. This study investigated changes in gene expression across three different tissues from the same mouse to examine how aging and early stage CR influence gene expression in different tissues of an organism. Expression profiling of heart, liver, and hypothalamus tissues was done in young (4-6 months) ad libitum fed (AL), young CR (2.5-4.5 months of CR), and old (26-28 months) AL male C57BL/6 mice. Aging significantly altered the expressions of 309, 1819, and 1085 genes in heart, liver, and hypothalamus tissues, respectively. In nine genes, aging altered expression across all three tissues although the regulation directions did not agree across all three tissues for some genes. Early stage CR in young mice significantly changed the expressions of 192, 839, and 100 genes in heart, liver, and hypothalamus tissues, respectively, and seven genes altered expression across all three tissues; three were up regulated and four were down regulated. The results of Gene Ontology (GO) Biological Process analysis indicated up regulation of antigen processing/presentation genes by aging and down regulation of stress response genes by early stage CR in all three tissues. The comparison of the results of aging and short term CR studies showed there were 389 genes, 18 GO biological processes, and 20 GO molecular functions in common.

Aging↗

PubMed2005

Early hypothalamic response to age-dependent gene expression by calorie restriction.

Molecular events linking the initial detection of calorie restriction (CR) to changes in gene expression throughout the organism that ultimately retard aging in CR animals are unknown. This study measured changes in gene expression induced by CR and by aging in the hypothalamus, which likely plays a central role in the initial perception of and response to CR. Hypothalamic expression profiling was done in young (4-6 months) ad libitum fed (AL), young CR (2.5-4.5 months of CR), and old (26-28 months) AL male C57BL/6 mice. CR altered the expression of 137 genes and aging altered 1222. Only 8 age-related genes were oppositely regulated by CR. To test whether reduced plasma glucose is a signal in altering hypothalamic gene expression, we examined GLUT4 transgenic mice (C57BL/6 background; 4-6 months), which have reduced plasma glucose similar to that of CR mice. Twenty-seven genes differed between transgenic and non-transgenic mice; nine of these were only altered by CR. The decreased plasma glucose had a limited role in CR mediated hypothalamic gene expression.

Aging↗

PubMed2005

Microarray evaluation of dietary restriction.

Dietary restriction (DR) extends the life span and retards many age-related cellular and molecular changes in laboratory rodents. However, neither its underlying mechanism nor the limits of its action are fully understood. In this review, we assessed the effect of DR on gene expression in vertebrate and invertebrate animals using data generated by microarrays. Altered genes in DR mice reported in 15 articles published since 1999 were compared. A comparison of altered genes by DR in mice, rats, pigs, monkeys, yeast, and flies showed no common gene altered by DR among different species. It seems that individual genes altered in the expression by DR were constrained within species. When we compared the functions of altered genes across all species, we found that certain functions such as metabolism, energy metabolism, stress and immune response, cell growth, and transcription regulation were shared among species. Although individual genes seem to be affected by DR differently among species, the overall physiologic influence of DR may be similar.

Animals↗

PubMed2004

Reproducibility, sources of variability, pooling, and sample size: important considerations for the design of high-density oligonucleotide array experiments.

We have undertaken a series of experiments to examine several issues that directly affect design of gene expression studies using Affymetrix GeneChip arrays: probe-level analysis, need for technical replication, relative contribution of various sources of variability, and utility of pooling RNA from different samples. Probe-level data were analyzed by Affymetrix MAS 5.0, and three model-based methods, PM-MM and PM-only models by dChip, and the RMA model by Bioconductor, with the latter two providing the best performance. We found that replicate chips of the same RNA have limited value in reducing total variability, and for relatively highly expressed genes in this biologically homogeneous animal model of aging, about 11% of total variation is due to day effects and the remainder is approximately equally split between sample and residual sources. We also found that pooling samples is neither advantageous nor detrimental. Finally we suggest a strategy for sample size calculations using formulas appropriate when coefficients of variation are known, target effects are expressed as fold changes, and data can be assumed to be approximately lognormally distributed.

Animals↗

PubMed2004

Hepatic genes altered in expression by food restriction are not influenced by the low plasma glucose level in young male GLUT4 transgenic mice.

Because food restriction (FR) has a profound effect on most tissues, it is plausible that the modulation of aging by FR occurs through cellular processes such as gene expression. The effect of FR in lowering plasma glucose levels has been demonstrated in mice, rats, and nonhuman primates. The consistency of this finding suggests that decreased plasma glucose may be an important consequence of FR. Indeed, lowering plasma glucose in the absence of FR would be expected to change the expression of some of the same genes as seen with FR. GLUT4 transgenic (TG) mice were particularly suited to this examination because they have low plasma glucose levels like FR mice. We investigated altered gene expression by FR and the effect of low plasma glucose levels caused by genetic manipulation by measuring mRNA expression in liver tissues of 4- to 6-mo-old mice with 2.5-4.5 mo of FR using microarrays and 4 groups: GLUT4 TG (C57BL/6 background) consumed food ad libitum (AL), GLUT4 TG FR, wild-type littermates AL, and wild-type littermates FR. The 3 statistical analysis methods commonly indicated that FR altered the expression of 1277 genes; however, none of these genes was altered by additional GLUT4 expression. In fact, the low plasma glucose level in GLUT4 TG mice did not affect gene expression. Some results were confirmed by real-time quantitative RT-PCR. We conclude that a low plasma glucose level does not contribute to or coincide with the effect of FR on gene expression in the liver.

Animals↗

PubMed2004

SAS programs for real-time RT-PCR having multiple independent samples.

Relative real-time reverse transcription PCR (RT-PCR) has become an important tool for quantifying changes in messenger RNA (mRNA) populations following differential development or stimulation of tissues or cells. However, the best methods for conducting such experiments and analyzing the resultant data remain an issue of discussion. In this report we describe an appropriate experimental methodology and the computer programs necessary to generate a meaningful statistical analysis of the combined biological and experimental variability in such experiments. Specifically, logarithmic transformations of raw fluorescence data from the log-linear portion of real-time PCR growth curves for both target and reference genes are analyzed using a SAS/STAT Mixed Procedure program specifically designed to give a point estimate of the relative expression ratio of the target gene with associated 95% confidence interval. The program code is open-source and is printed in the text.

Algorithms↗