Aging-associated changes in cardiac gene expression

Abstract

Cardiovascular diseases (e.g., vascular diseases, strokes, heart failure) reach epidemic proportions in the elderly and are the primary limits to survival in man. Age-associated changes in heart structure and function represent the major risk factors in heart failure (HF) syndromes and are associated with altered patterns of gene expression that can generally be seen as relative changes in the abundance of gene transcripts. An understanding of the molecular mechanisms underlying these changes should be tantamount to defining a genetic basis for aging; however, the analysis of processes as complicated as aging requires an accounting of biological diversity. Until recently, most of the changes in transcript abundance were identified one at a time, but the advent of gene expression arrays has permitted rapid, large-scale expression profiling. This has provided information about the dynamics of total gene expression, which can be used to identify pathways and elucidate regulatory events that may be affected during senescence or in response to disease. Importantly, very large sample sizes or meta-analyses of studies of smaller sample sizes should be sufficient to account for the diversity of altered gene expression that directs alterations in specific molecular pathways, which underlie changes in cardiac structure and function in senescence and disease.

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…Aging and Ischemic Preconditioning. Several genes are differentially expressed in the aged myocardium (Volkova et al, 2005), among them genes encoding proteins involved in the signal transduction of preconditioning-induced cardioprotection (Taylor and Starnes, 2003). For example, the PKC content, which is central to the signal transduction cascade of ischemic preconditioning in juvenile animal hearts (section II.B.5.…”

Molecular mechanisms of cardiomyocyte aging

“…Numerous transcripts encoding factors associated with signalling pathways are also altered [38]. AT 1 R and AT 2 R [AngII (angiotensin II) receptor subtypes 1 and 2 respectively] [39], COX-2 (cyclooxygenase 2), β -arrestin and the transcription factor NF- κ B (nuclear factor κ B) increase with age, whereas cardiac transcripts/proteins to the M 2 -cholinoreceptor, ET A receptor [ET (endothelin) receptor subtype A] [40], β 1 -adrenergic receptor, the α -subunit of G s proteins, adenylate cyclases and the oestrogen receptor diminish with age [4,41–43]. Transcripts to collagens type I and III decrease, but some changes are chamber-specific [44,45].…”

“…In individuals <65 years of age, ~1 % suffer from HF [3]; however, heart-related disease syndromes reach epidemic proportions in the very old (≥80 years of age). In fact, more than 10% of the very old will be afflicted with some form of heart disease [3,4]. …”

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

“…Factors such as DNA and/or protein damage due to increased oxidative stress or late-acting mutations could account for the adverse effects of aging on myocyte structure and function (4)(5)(6)(7)(8). However, molecular bases underlying the increased propensity to arrhythmogenesis in the elderly remain incompletely understood.…”