Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes

Goyns, M.H.; Charlton, M.A; Dunford, J E; Lavery, W. Lindsay; Merry, B.J.; Salehi, Mansoor; Simoes, D. De C.M.

doi:10.1016/s0047-6374(97)00166-8

Cited by 48 publications

(31 citation statements)

References 34 publications

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“…For instance, these microarrays have been used to study age-based changes in global gene expression in rodents (29,39,49), monkeys (24), and humans (58,59). These studies have demonstrated that between 1 and 5% of mRNAs are differentially expressed in skeletal muscle with aging (16,29,39,59). In general, these studies have reported changes in gene expression consistent with decreased protein synthesis, impaired oxidative defense, and decreased activity of mitochondrial proteins, differential expression of genes involved in energy metabolism, DNA damage repair, stress response, immune/inflammatory response, RNA binding and splicing, and proteasome degradation.…”

Section: Discussionmentioning

confidence: 99%

“…To begin to identify the molecular basis for the loss of muscle mass with age, investigators have measured changes in expression on a global scale during aging in skeletal muscle using differential display (16), serial analysis of gene expression (57), cDNA arrays (23,43), and oligonucleotide-based microarrays (24,29,38,59). These studies have reported changes in gene expression consistent with decreased protein synthesis, impaired oxidative defense, and decreased activity of mitochondrial proteins.…”

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confidence: 99%

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Identification of a molecular signature of sarcopenia

Giresi

Stevenson

Theilhaber³

et al. 2005

Physiological Genomics

217

152

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Investigating the molecular mechanisms underlying sarcopenia in humans with the use of microarrays has been complicated by low sample size and the variability inherent in human gene expression profiles. We have conducted a study using Affymetrix GeneChips to identify a molecular signature of aged skeletal muscle. The molecular signature was defined as the set of expressed genes that best distinguished the vastus lateralis muscle of young ( n = 10) and older ( n = 12) male subjects, when a k-nearest neighbor supervised classification method was used in conjunction with a signal-to-noise ratio gene selection method and a holdout cross-validation procedure. The age-specific expression signature was comprised of 45 genes; 27 were upregulated and 18 were downregulated. This signature also correctly classified 75% of the muscle samples from young and older subjects published by an independent laboratory, based on their expression profiles. The signature revealed increased expression of several genes involved in mediating cellular responses to inflammation and apoptosis, including complement component C1QA, Galectin-1, C/EBP-β, and FOXO3A, among others. The increased expressions of genes that regulate pre-mRNA splicing, localization, and modification of RNA comprise markers of the aging signature. Downregulated genes in the signature were the glutamine transporter SLC38A1, a TRAF-6 inhibitory zinc finger protein, and membrane-bound transcription factor protease S2P, among others. The sarcopenia signature developed here will be useful as a molecular model to judge the effectiveness of exercise and other therapeutic treatments aimed at ameliorating the effects of muscle loss associated with aging.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Identification of a molecular signature of sarcopenia

Giresi

Stevenson

Theilhaber³

et al. 2005

Physiological Genomics

217

152

View full text Add to dashboard Cite

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“…This difference has been suggested by several authors to be due to a diminished ability of older rats to respond to myocardial ischemia compared to younger rats. 40,41 Stereological techniques using random sampling and a grid micrometer permitted quantification and statistical analysis of atypical cardiac cell populations. Although specific cell types were not differentiated, noncardiac cell type volume fractions indicated significant cardiotoxicity among treatment groups due to pyknotic nuclei and the infiltration of inflammatory cells.…”

Section: Figmentioning

confidence: 99%

Combined Effects of Ephedrine-Containing Dietary Supplements, Caffeine, and Nicotine on Morphology and Ultrastructure of Rat Hearts

Brown

Trauth

Grippo

et al. 2012

Journal of Caffeine Research

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Cigarette smokers have an increased risk for coronary artery disease. Nicotine present in cigarettes can adversely affect the cardiovascular system via stimulation of both sympathetic and parasympathetic neurons. Caffeine, another cardiovascular and central nervous system (CNS) stimulant, is commonly found in Ephedra and Ephedra-free dietary supplements. These caffeine-containing supplements also have been linked to cardiovascular toxicities. Although no longer on the U.S market, Ephedra-containing supplements are another source of cardiovascular and CNS stimulants, namely the ephedrine alkaloids. Together caffeine, nicotine, and ephedrine can individually stress the cardiovascular system, and an overlap of these agents is predicted in smokers and dieters. To understand the collective effects of these stimulants on the heart morphology and ultrastructure, rats were exposed to synthetic combinations of nicotine (0.2 mg/kg/day), ephedrine (0-30 mg/kg/day), and/or caffeine (0-24 mg/kg/day) as well as an extract from a caffeine-containing Ephedra supplement (Metabolife 356). After exposure for 3 days, the hearts were removed and examined for hypersensitivity myocarditis and myocardial necrosis. None of the drugs tested alone affected heart tissue morphology, nor were atypical cardiac cells observed. However, in combination, significant interactions were found between caffeine and ephedrine; the interventricular septum was most susceptible, with a significant increase in atypical cardiac cells observed. Nicotine pretreatment caused greater susceptibility to cardiotoxicity associated with combinations of caffeine + ephedrine or Metabolife, particularly in the left ventricle wall. These results indicate that sympathomimetic combinations present in Ephedra supplements may have produced cardiotoxicity reported in consumers of these products. Moreover, the presence of nicotine exacerbates these toxic effects.

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“…Many changes in gene expression have been observed during aging in many organisms, from unicellular yeast to primates [33,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85]. Differential screening of cDNA libraries isolated from young and old mice identified genes in which protein products are involved in many different cellular processes.…”

Section: Age-related Differential Gene Expressionmentioning

confidence: 99%

“…Differential display techniques were also used to survey gene expression during aging of the rat brain, heart, and liver [77,81]. The results in the brain identified age-related changes in the expression of the gene fos encoding one of the monomers of the dimeric AP1 transcription factor.…”

Section: Age-related Differential Gene Expressionmentioning

confidence: 99%

Differential Gene Expression and Aging

Seroude

2002

The Scientific World JOURNAL

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It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

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Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes

Cited by 48 publications

References 34 publications

Identification of a molecular signature of sarcopenia

Identification of a molecular signature of sarcopenia

Combined Effects of Ephedrine-Containing Dietary Supplements, Caffeine, and Nicotine on Morphology and Ultrastructure of Rat Hearts

Differential Gene Expression and Aging

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