Abstract:
:To facilitate the development of assays for the discovery of pharmaceuticals capable of mimicking the effects of caloric restriction (CR) on life- and healthspan (CR mimetics), we evaluated the effectiveness of glucoregulatory and putative cancer chemopreventatives in reproducing the hepatic gene expression profile produced by long-term CR (LTCR), using Affymetrix microarrays. We have shown that CR initiated late in life begins to extend lifespan, reduce cancer as a cause of death, and reproduce approximately three-quarters of the genomic effects of LTCR in 8 wk (CR8). Eight weeks of metformin treatment was superior to CR8 at reproducing LTCR-like gene expression changes, maintaining a superior number of such changes over a broad range of statistical stringencies, and producing more Gene Ontology terms overlapping those produced by LTCR. Consistent with these results, metformin has been shown to reduce cancer incidence in mice and humans. Phenformin, a chemical cousin of metformin, extends lifespan and reduces tumor incidence in mice. Taken together, these results indicate that gene expression biomarkers can be used to identify promising candidate CR mimetics.
journal_name
Physiol Genomicsjournal_title
Physiological genomicsauthors
Dhahbi JM,Mote PL,Fahy GM,Spindler SRdoi
10.1152/physiolgenomics.00069.2005subject
Has Abstractpub_date
2005-11-17 00:00:00pages
343-50issue
3eissn
1094-8341issn
1531-2267pii
00069.2005journal_volume
23pub_type
杂志文章abstract::Current models in skeletal muscle biology do not fully account for the breadth, causes, and consequences of phenotypic variation among skeletal muscle groups. The muscle allotype concept arose to explain frank differences between limb, masticatory, and extraocular (EOM) muscles, but there is little understanding of th...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00222.2003
更新日期:2004-07-08 00:00:00
abstract::In functional genomics, the high-throughput methods such as microarrays 1) allow analysis of the relationships between genes considering them as elements of a network and 2) lead to biological interpretations thanks to Gene Ontology. But up to now it has not been possible to find relationships between the functions an...
journal_title:Physiological genomics
pub_type: 杂志文章,meta分析
doi:10.1152/physiolgenomics.00008.2008
更新日期:2008-06-12 00:00:00
abstract::Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. Under normal conditions, D(1)-like receptors (D(1) and D(5)) inhibit sodium transport in the kidney and intestine. However, in the Dahl salt-sensitive and spontaneou...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00127.2004
更新日期:2004-11-17 00:00:00
abstract::Leptin is known as a cytokine mostly produced by fat cells and implicated in regulation of energy metabolism and food intake but has also been shown to be involved in many physiological mechanisms such as tissue metabolism and cell differentiation and proliferation. In particular, leptin influences the development of ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00020.2013
更新日期:2013-08-01 00:00:00
abstract::Growth hormone is one of few pharmacologic agents known to augment milk production in humans. We hypothesized that recombinant human GH (rhGH) increases the expression of cell proliferation and milk protein synthesis genes. Sequential milk and blood samples collected over four days were obtained from five normal lacta...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00079.2010
更新日期:2011-04-27 00:00:00
abstract::We previously mapped several gene loci influencing cancer risk of inbred BDIV and BDIX rats, resistant and susceptible, respectively, to N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNSTs). On the basis of a genomewide association analysis using a (BDIV × BDIX) F(2) generation the Mss...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00246.2010
更新日期:2011-05-01 00:00:00
abstract::Metazoan akirin genes regulate innate immunity, myogenesis, and carcinogenesis. Invertebrates typically have one family member, while most tetrapod and teleost vertebrates have one to three. We demonstrate an expanded repertoire of eight family members in genomes of four salmonid fishes, owing to paralog preservation ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00045.2010
更新日期:2010-06-01 00:00:00
abstract::The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. miR-29s are encoded by two gene clusters. Binding sites for several transcriptional factors have been identified in the promoter regions of miR-29 genes. The miR-29 family members share a common seed region sequence and are p...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00141.2011
更新日期:2012-02-27 00:00:00
abstract::An increased phospholamban (PLB)-to-sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) ratio has been suggested to contribute to the slowing of relaxation in failing human ventricle. We have used an adenoviral vector carrying the sequence for PLB to increase this ratio in isolated adult rat ventricular myocytes, and w...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.1999.1.2.41
更新日期:1999-08-31 00:00:00
abstract::Megakaryocyte (MK) development is critically informed by plasma membrane-localized receptors that integrate a multiplicity of environmental cues. Given that the current understanding about receptors and ligands involved in megakaryocytopoiesis is based on single targets, we performed a genome-wide search to identify a...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00056.2012
更新日期:2013-03-18 00:00:00
abstract::The nucleus tractus solitarii (NTS) controls the cardiovascular system during exercise, and alteration of its function may underlie exercise-induced cardiovascular adaptation. To understand the molecular basis of the NTS's plasticity in regulating blood pressure (BP) and its potential contribution to the antihypertens...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00074.2012
更新日期:2013-01-07 00:00:00
abstract::The purpose of this study was to identify novel transcriptional events occurring in the aortic wall before angiogenesis. We used a defined tissue culture system that takes advantage of the capacity of rat aortic rings to generate neovessels ex vivo in response to angiogenic factor stimulation. Total RNA isolated from ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00048.2006
更新日期:2006-10-03 00:00:00
abstract::The genetic basis of susceptibility to pulmonary fibrosis is largely unknown. Initially, in this study, loci regulating the response of bleomycin-induced pulmonary fibrosis were mapped using a set of recombinant congenic strains bred from pulmonary fibrosis-resistant A/J and susceptible C57BL/6J (B6) mice. Linkage was...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00095.2005
更新日期:2005-09-21 00:00:00
abstract::Studies were performed to examine the extent to which mechanical stimuli mediate control of angiogenesis in bladder cells both in vitro and in vivo. Differential gene expression between control nonstretched and cyclically stretched bladder smooth muscle cells was assessed using oligonucleotide microarrays and pathway ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.90291.2008
更新日期:2008-12-12 00:00:00
abstract::In recent years, it has become evident that the adult mammalian CNS contains a population of neural stem cells (NSCs) described as immature, undifferentiated, multipotent cells, that may be called upon for repair in neurodegenerative and demyelinating diseases. NSCs may give rise to oligodendrocyte progenitor cells (O...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00021.2002
更新日期:2003-08-15 00:00:00
abstract::Peroxisome proliferator-activated receptor type gamma (PPARgamma) is a subgroup of the PPAR transcription factor family. Recent studies indicate that loss of PPARgamma is associated with the development of pulmonary hypertension (PH). We hypothesized that the endothelial dysfunction associated with PPARgamma inhibitio...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00094.2009
更新日期:2009-12-30 00:00:00
abstract::Essential hypertension is highly prevalent in the elderly population, exceeding 70% in people older than 60 yr of age, and remains a leading risk factor for heart disease, stroke, and chronic renal disease. Elucidation of genetic determinants is critical but remains a challenge due to its complex, multifactorial patho...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00012.2011
更新日期:2011-11-07 00:00:00
abstract::Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain amino...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00055.2015
更新日期:2015-11-01 00:00:00
abstract::Previously we demonstrated that aging in coronary arteries is associated with proinflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by enhancing endothelial apoptosis. To test this hypothesis we characterized proapoptotic alterations in the phenotype of ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00136.2003
更新日期:2004-03-12 00:00:00
abstract::Dahl salt-sensitive SS and consomic, salt-resistant SS-13(BN)/Mcw rats possess a highly similar genetic background but exhibit substantial differences in blood pressure salt sensitivity. We used cDNA microarrays to examine sequential changes of mRNA expression of approximately 2,000 currently known rat genes in the re...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00089.2002
更新日期:2003-02-06 00:00:00
abstract::C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30-40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unkn...
journal_title:Physiological genomics
pub_type: 杂志文章,多中心研究
doi:10.1152/physiolgenomics.00054.2005
更新日期:2006-10-11 00:00:00
abstract::The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00015.2015
更新日期:2015-10-01 00:00:00
abstract::In type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, the pathogenic destruction of the insulin-producing pancreatic beta-cells is under the control of and influenced by distinct subsets of T lymphocytes. To identify the critical genes expressed by autoimmune T cells, antigen presenting cells, and pan...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00173.2004
更新日期:2005-04-14 00:00:00
abstract::As the amount of information available to biologists increases exponentially, data analysis becomes progressively more challenging. Sequence homology has been a traditional tool in the researchers' armamentarium; it is a very versatile instrument and can be employed to assist in numerous tasks, from establishing the f...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00112.2002
更新日期:2002-12-03 00:00:00
abstract::A microarray study of the effect of senescence in mice on gene expression in muscle has been published recently. The present analysis was done to evaluate the extent to which the age-related differences in gene expression in murine muscle are also evident in human muscle. RNA extracted from muscle of young (21-24 yr) ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.2001.5.2.67
更新日期:2001-03-08 00:00:00
abstract::Cardiac microvascular endothelial cells (CMVECs) are the most numerous cells in the myocardium and orchestrate cardiogenesis during development, regulate adult cardiac function, and modulate pathophysiology of heart failure. It has been shown that the transcriptome of CMVECs differs from other endothelial cell types, ...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00002.2019
更新日期:2019-06-01 00:00:00
abstract::Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of the osterix promoter. To test the role of NFE2L1 in regulating bone formation in v...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00105.2009
更新日期:2010-01-08 00:00:00
abstract::We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the freq...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00048.2002
更新日期:2002-10-29 00:00:00
abstract::Preeclampsia (PE) is a devastating adverse outcome of pregnancy. Characterized by maternal hypertension, PE, when left untreated, can result in death of both mother and baby. The cause of PE remains unknown, and there is no way to predict which women will develop PE during pregnancy. The only known treatment is delive...
journal_title:Physiological genomics
pub_type: 杂志文章,评审
doi:10.1152/physiolgenomics.00102.2018
更新日期:2019-03-01 00:00:00
abstract::A high-resolution time series of transcript abundance was generated to describe global expression dynamics in response to nutrition in Drosophila. Nonparametric change-point statistics revealed that within 7 h of feeding upon yeast, transcript levels changed significantly for approximately 3,500 genes or 20% of the Dr...
journal_title:Physiological genomics
pub_type: 杂志文章
doi:10.1152/physiolgenomics.00061.2006
更新日期:2007-03-14 00:00:00