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Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts(More)
Increased activation of the renin-angiotensin-aldosterone system (RAAS) and an increase in oxidative stress are both implicated in age-related cardiac remodeling but their precise interrelationship and linkage to underlying molecular and cellular abnormalities remain to be defined. Recent studies indicate that NADPH oxidases are major sources of oxidative(More)
PURPOSE OF REVIEW Age-associated arterial alterations in cells, matrix, and biomolecules are the foundation for the initiation and progression of cardiovascular diseases in older persons. This review focuses on the latest advances on the intertwining of aging and disease within the arterial wall at the cell and molecular levels. RECENT FINDINGS(More)
To elucidate potential mechanisms of enhanced type 2 matrix metalloprotease levels and activity within the thickened aged rat aorta, the present study measured its mRNA and protein levels and those of its membrane bound activator, MT1-MMP, its endogenous tissue inhibitor, TIMP-2, tissue type, and urokinase plasminogen activators and their receptors, and an(More)
OBJECTIVE To study matrix metalloproteinase 2 (MMP-2) effects on transforming growth factor-beta1 (TGF-beta1) activation status and downstream signaling during arterial aging. METHODS AND RESULTS Western blotting and immunostaining showed that latent and activated TGF-beta1 are markedly increased within the aorta of aged Fisher 344 cross-bred Brown Norway(More)
Arterial aging is a predominant risk factor for the onset of cardiovascular diseases, such as hypertension, myocardial infarction, or stroke. Aging is associated with intravascular renin-angiotensin system activation, increased vascular stiffness, intima-media thickening, and a proinflammatory phenotype. Little is known about the influence of aldosterone on(More)
The poly(A) binding protein (PABP), a conserved protein that binds to the 3' poly(A) tail on mRNAs in eukaryotic cells, has been implicated in the regulation of mRNA stability and translation. Two PABP cDNAs with different sequences were isolated from mouse testis cDNA libraries. The predicted amino acid sequence of one, PABP1, is nearly identical (98.9%)(More)
Aging promotes oxidative stress in vascular endothelial and smooth muscle cells, which contribute to the development of cardiovascular diseases. NF-E2-related factor 2 (Nrf2) is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals, leading to adaptive upregulation of numerous reactive oxygen species(More)
The aging population is increasing dramatically. Aging-associated stress simultaneously drives proinflammatory remodeling, involving angiotensin II and other factors, in both the heart and large arteries. The structural remodeling and functional changes that occur with aging include cardiac and vascular wall stiffening, systolic hypertension and suboptimal(More)
One of the major conceptual advances in our understanding of the pathogenesis of age-associated cardiovascular diseases has been the insight that age-related oxidative stress may promote vascular inflammation even in the absence of traditional risk factors associated with atherogenesis (e.g., hypertension or metabolic diseases). In the present review we(More)