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Oxidative injury and inflammation are intimately involved in the aging process and the development of age-related diseases. To date, most nutritional antiaging strategies have focused solely on the delivery of exogenous antioxidants to combat the negative effects of aging. A promising new strategy is to identify nutrients and phytochemicals that can directly target intrinsic cytoprotective mechanisms, including modulation of the expression of (1) genes involved in the detoxification of xenobiotics, (2) genes involved in the synthesis and regulation of intrinsic antioxidants and antioxidant enzymes, (3) genes involved in the regulation of inflammation, and (4) vitagenes. The purpose of this review is to provide an overview of the age-related changes in gene expression related to oxidative stress, detoxification, and inflammatory processes, and to discuss natural compounds with the potential to oppose age-related changes in gene expression related to these processes, which therefore may be suitable for use in human antiaging research. [ABSTRACT FROM AUTHOR]

Advanced glycation endproducts (AGEs) and their precursor dicarbonyls are generally perceived as having adverse health effects. They are also considered to be initiators and promoters of disease and aging. However, proof for a causal relationship is lacking. On the other hand, it is known that AGEs and melanoidins possess beneficial properties, such as antioxidant and metal-chelating activities. Furthermore, some AGEs may stimulate the cellular detoxification system, generally known as the phase II drug metabolizing system. We show here that several reactive dicarbonyl intermediates have the capability to stimulate the cellular phase II detoxification systems in both a reporter cell line and primary rat hepatocytes. In addition, we demonstrate that dicarbonyls can attenuate the inflammatory signaling induced by tumor necrosis factor-α in a reporter cell system. [ABSTRACT FROM AUTHOR]

Cancer is potentially preventable disease. A surprising variety of intracellular pathways can be a target for chemoprevention. Earlier it was discovered that cAMP-mediated system can play important role in prevention of DMBA-mammary carcinogenesis. There are two types of cAMP-dependent protein kinases (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunits, but contain distinct regulatory (R) ones, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIα) correlates with tumorogenesis and tumor growth. It was found that downregulation of RIα by 21-mer antisense oligonucleotide led to growth arrest of cancer cells. The effect of RIα antisense oligonucleotide correlated with a decrease in RIα protein and a concomitant increase in RII protein level. It was shown that antisense RIα can protect in a sequence-specific manner from 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. At 90 days after DMBA intubation, RIα-antisense-treated rats exhibited significantly lower number of tumors per rat, than untreated control animals. The antisense also delayed the first tumor appearance. An increase in RIα and PKA-I levels in the mammary gland and liver preceded tumor production, and antisense downregulation of RI restored normal levels of PKA-I and PKA-II in these tissues. Antisense RI in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein-1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary gland, antisense RIα promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIα. The results demonstrate that RIα antisense produces dual anticarcinogenic effects : (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and AP1 directed transcription; and (b) activating DNA repair processes in the mammary gland by downregulating of PKA-1. [ABSTRACT FROM AUTHOR]