Abstract:
:Aging of somatic cells can be defined as the gradual loss of the information embedded in the global and local properties of complex macromolecular networks. This loss of information may reflect the dynamic interplay between stochastic factors, such as the accumulation of unrepaired somatic damage, and gene-encoded programmatic responses. This would ultimately result in loss of function, impaired response to environmental challenge, and a progressively increased incidence of disease. Here the authors present the case for aging as a continuous battle between maintaining genomic integrity and ensuring sufficient cell functional mass. Focusing on aging of the liver in rodents, evidence is presented that normal aging is associated with a gradual accumulation of random alterations in the DNA of the genome as a consequence of imperfect DNA repair and a decrease in the rate of DNA damage-induced apoptosis. Apoptosis is the cell's genome maintenance mechanism of last resort and an imbalance towards apoptosis can contribute to manifestations of aging-related phenotypes, as exemplified by mouse models of premature aging due to genetic defects in genome maintenance. Prospects to reset the clock in this zero sum game between survival and the maintenance of phenotypic integrity will be discussed.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Suh Y,Vijg Jdoi
10.1089/ars.2006.8.559subject
Has Abstractpub_date
2006-03-01 00:00:00pages
559-71issue
3-4eissn
1523-0864issn
1557-7716journal_volume
8pub_type
杂志文章,评审abstract::The cellular redox state is associated with major cellular processes including differentiation, transformation, and apoptosis. Glutaredoxin 2 (Grx2) is a mitochondrial oxidoreductase suggested to play a critical role in protection against apoptotic stimuli. An alternative Grx2 transcript variant encoding a nonmitochon...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1821
更新日期:2008-03-01 00:00:00
abstract::Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra zona compacta, and in other subcortical nuclei associated with a widespread occurrence of Lewy bodies. The causes of cell death in Parkinson's disease are still poorly understood, but a defect in mitochondrial ox...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308603322110832
更新日期:2003-06-01 00:00:00
abstract::This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3930
更新日期:2011-05-15 00:00:00
abstract:UNLABELLED:In living systems, the mechanisms of inheritance involving gene expression are operated by (i) the traditional model of genetics where the deoxyribonucleic acid (DNA) transcription and messenger ribonucleic acid stability are influenced by the DNA sequences and any aberrations in the primary DNA sequences an...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4600
更新日期:2012-07-15 00:00:00
abstract::The 6(th) COSTAM/SFRR (ASEAN/Malaysia) workshop, "Micronutrients, Oxidative Stress, and the Environment," was held from June 29 to July 2 at Holiday Inn Damai Beach Resort in Kuching, Sarawak. Two hundred twenty participants from 17 countries presented recent advances on natural antioxidants in the area of oxidative s...
journal_title:Antioxidants & redox signaling
pub_type:
doi:10.1089/ars.2006.8.2175
更新日期:2006-11-01 00:00:00
abstract:AIMS:Peripheral artery disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to ischemia is urgently needed to improve therapeutic options. The aim of this study is to investigate hypoxia-induced miR-210 regulation ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5206
更新日期:2014-09-10 00:00:00
abstract::The herbicide paraquat (PQ) has been implicated as a potential risk factor for the development of Parkinson's disease. In this study, PQ (0.5-1 microM) was shown to be selectively toxic to dopaminergic (DA) neurons through the activation of microglial NADPH oxidase and the generation of superoxide. Neuron-glia culture...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.654
更新日期:2005-05-01 00:00:00
abstract:SIGNIFICANCE:A mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow--hypoxic vasodilation--occur in an attempt to restore oxygen supply. Nitric oxide (NO) is a major signaling...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4979
更新日期:2013-11-10 00:00:00
abstract::Hemoglobin is considered a potentially toxic molecule when released from erythrocytes during hemolysis, inflammation, or tissue injury. The mechanisms of toxicity involve reduced nitric oxide bioavailability and oxidative processes both occurring at the heme prosthetic groups. When the endogenous oxidant H(2)O(2) reac...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2009.2826
更新日期:2010-02-01 00:00:00
abstract::The phagocytic NADPH oxidase is recognized as a critical component of innate immunity, responsible for generation of microbicidal reactive oxygen species (ROS). This enzyme is one representative of the Nox family of oxidases (Nox1-Nox5, Duox1, and Duox2) that exhibit diverse expression patterns and appear to serve a v...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1549
更新日期:2006-09-01 00:00:00
abstract::Oxidative stress plays a significant role in the pathogenesis of coronary artery disease (CAD). A p22(phox)-based NAD(P)H oxidase acts as a potent superoxide-generating system in the vasculature. We studied the association of the A640G and the C242T polymorphisms with clinical risk factors, endothelial function, and s...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/15230860260220184
更新日期:2002-08-01 00:00:00
abstract:AIMS:Monothiol glutaredoxins (1-C-Grxs) are small proteins linked to the cellular iron and redox metabolism. Trypanosoma brucei brucei, model organism for human African trypanosomiasis, expresses three 1-C-Grxs. 1-C-Grx1 is a highly abundant mitochondrial protein capable to bind an iron-sulfur cluster (ISC) in vitro us...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4859
更新日期:2013-09-01 00:00:00
abstract::Accumulating evidence suggests that oxidative stress associated with impaired metabolism of the antioxidant glutathione (GSH) plays a key role in the pathophysiology of schizophrenia. Magnetic resonance spectroscopy (MRS) is one of the brain-imaging techniques that can quantitatively measure bioactive substances such ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3453
更新日期:2011-10-01 00:00:00
abstract:SIGNIFICANCE:Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is c...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6802
更新日期:2016-12-01 00:00:00
abstract::NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4987
更新日期:2013-04-20 00:00:00
abstract::Homocysteine is a thiol-containing amino acid that has gained notoriety because its elevation in the plasma is correlated with complex and multifactorial diseases, including cardiovascular diseases, neurodegenerative diseases, and neural tube defects. Homocysteine is redox-active, and its toxic effects have been frequ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.547
更新日期:2005-05-01 00:00:00
abstract:SIGNIFICANCE:Ascorbic acid and sodium-dependent vitamin C transporters (SVCT) have been shown to have important functions in the peripheral nervous system (PNS). Ascorbic acid is known to promote myelination in vitro in Schwann cell/dorsal root ganglion co-cultures by the formation of a collagen- and laminin-containing...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5380
更新日期:2013-12-10 00:00:00
abstract:SIGNIFICANCE:Oxidative (reactive oxygen species [ROS]) and nitrosative (reactive nitrogen species [RNS]) stress affects many physiological processes, including survival and death. Although high levels of ROS/RNS mainly causes cell death, low levels of free radicals directly modulate the activities of transcriptional fa...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5746
更新日期:2014-07-01 00:00:00
abstract:AIMS:Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through protein kinas...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4534
更新日期:2013-03-20 00:00:00
abstract:AIMS:The potential receptor for hydrogen sulfide (H2S) remains unknown. RESULTS:H2S could directly activate vascular endothelial growth factor receptor 2 (VEGFR2) and that a small interfering RNA (siRNA)-mediated knockdown of VEGFR2 inhibited H2S-induced migration of human vascular endothelial cells. H2S promoted angi...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4565
更新日期:2013-08-10 00:00:00
abstract:AIMS:Protein S-glutathionylation, the formation of a mixed disulfide between glutathione and protein thiols, is an oxidative modification that has emerged as a new signaling paradigm, potentially linking oxidative stress to chronic inflammation associated with heart disease, diabetes, cancer, lung disease, and aging. U...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6531
更新日期:2016-11-20 00:00:00
abstract::Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protect...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601750100588
更新日期:2001-02-01 00:00:00
abstract:SIGNIFICANCE:Oxidative stress and damage are well-established components of neurodegenerative diseases, contributing to neuronal death during disease progression. Here, we consider key K(+) channels as target proteins that can undergo oxidative modulation, describe what is understood about how this influences disease p...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6007
更新日期:2015-02-20 00:00:00
abstract:SIGNIFICANCE:Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diab...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2015.6293
更新日期:2015-06-10 00:00:00
abstract::Integrin-mediated phagocytosis in fibroblasts is associated to collagenase 1 induction when the particles are coated with high-affinity binding ligands. This study shows that the high density of ligand coating on the particle elicits RhoA-dependent particle uptake coupled to signal transduction. Integrin clustering in...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.318
更新日期:2005-03-01 00:00:00
abstract:SIGNIFICANCE:Ewan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific comm...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5372
更新日期:2013-12-10 00:00:00
abstract::Proteasome-mediated protein degradation is responsible for a large percentage of bulk protein turnover, particularly the degradation of short-lived and oxidized proteins. Increasing evidence suggests that proteasome inhibition occurs during the aging of the central nervous system (CNS), and in a variety of age-related...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.163
更新日期:2006-01-01 00:00:00
abstract::Although there is an abundance of evidence suggesting that insulin resistance plays a significant role in the vasculature, the precise mechanistic role involved still remains unclear. In this review, we discuss the current background of insulin resistance in the context of insulin signaling and action in the vasculatu...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1053
更新日期:2005-07-01 00:00:00
abstract:SIGNIFICANCE:Chagas disease (CD) affects several million people in Latin America and is spreading beyond its classical boundaries due to the migration of infected host and insect vectors, HIV co-infection, and blood transfusion. The current therapy is not adequate for treatment of the chronic phase of CD, and new drugs...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4618
更新日期:2013-09-01 00:00:00
abstract:SIGNIFICANCE:Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endoth...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2015.6554
更新日期:2016-09-01 00:00:00