Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress

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Title Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress
Author Ashton, Kevin John; Willems, Laura; Holmgren, Kirsty; Ferreira, Linda Anne; Headrick, John Patrick
Journal Name Experimental Gerontology
Editor Georg Wick and Beatrix Grubeck-Loebenstein
Year Published 2006
Place of publication New York, NY
Publisher Elsevier Inc
Abstract Aged hearts exhibit reduced tolerance to ischemia-reperfusion, together with altered structure and post-ischemic remodelling. The molecular bases of such changes are unclear. Using cDNA microarrays and quantitative RT-PCR we characterized shifts in gene expression patterns with aging in normoxic and post-ischemic (20 min global ischemia, 60 min reperfusion) murine hearts (young: 2-4 months; aged: 16-18 months). We identified an age-associated up-regulation of transcripts involved in cell death, oxygen transport and metabolism in normoxic hearts. Down-regulated transcripts were involved in transporter activity, protein binding and hydrolase activity, changes in MAPK, WNT and TGF-beta signalling with aging were also observed. Ischemic stress generated a much greater degree of contractile impairment and cellular damage in aged vs. young hearts. This was associated with a substantially modified transcriptional response, with selective changes in Ca2+, WNT, NOTCH and G-protein coupled receptor signalling paths in aged vs. young hearts. Despite some common responses to ischemia in young and aged hearts (induction of heat shock protein transcripts), aging selectively modified ischemic responses of immediate early genes, and genes involved in modulating apoptosis and remodelling/angiogenesis. In summary, aging is associated with shifts in cardiovascular gene expression consistent with the phenotypic features of older hearts. Reduced tolerance with age may be related to modification of signalling (particularly WNT and TGF-beta), and shifts in expression of immediate early genes, and genes important in control of cell death/survival, angiogenesis, and cardiac remodelling.
Peer Reviewed Yes
Published Yes
Volume 41
Issue Number 2
Edition 2006
Page from 189
Page to 204
ISSN 0531-5565
Date Accessioned 2006-07-02
Language en_AU
Research Centre Heart Foundation Research Centre; Menzies Health Institute Qld
Faculty Griffith Health Faculty
Subject Gene Expression; Medical and Health Sciences
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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