Markers of oxidant stress that are clinically relevant in aging and age-related disease

Jacob, Kimberly D.; Hooten, Nicole Noren; Trzeciak, Andrzej; Evans, Michele K.

doi:10.1016/j.mad.2013.02.008

Cited by 197 publications

(181 citation statements)

References 259 publications

(319 reference statements)

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“…Guanine is particularly sensitive to oxidation due to its low redox potential (17), and the product of guanine oxidation, 7,8-dihydro-8-oxoguanine, is routinely determined for monitoring oxidative DNA damage (21). ATP has a significantly higher redox potential compared with GTP (48) and is less sensitive toward oxidation.…”

Section: Discussionmentioning

confidence: 99%

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

Hannemann

Suppanz

et al. 2016

Antioxidants & Redox Signaling

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Aims: YchF/Ola1 are unconventional members of the universally conserved GTPase family because they preferentially hydrolyze ATP rather than GTP. These ATPases have been associated with various cellular processes and pathologies, including DNA repair, tumorigenesis, and apoptosis. In particular, a possible role in regulating the oxidative stress response has been suggested for both bacterial and human YchF/Ola1. In this study, we analyzed how YchF responds to oxidative stress and how it potentially regulates the antioxidant response. Results: Our data identify a redox-regulated monomer-dimer equilibrium of YchF as a key event in the functional cycle of YchF. Upon oxidative stress, the oxidation of a conserved and surface-exposed cysteine residue promotes YchF dimerization, which is accompanied by inhibition of the ATPase activity. No dimers were observed in a YchF mutant lacking this cysteine. In vitro, the YchF dimer is dissociated by thioredoxin 1 (TrxA) and this stimulates the ATPase activity. The physiological significance of the YchF-thioredoxin 1 interaction was demonstrated by in vivo cross-linking, which validated this interaction in living cells. This approach also revealed that both the ATPase domain and the helical domain of YchF are in contact with TrxA. Innovation: YchF/Ola1 are the first redox-regulated members of the universally conserved GTPase family and are inactivated by oxidation of a conserved cysteine residue within the nucleotide-binding motif. Conclusion: Our data provide novel insights into the regulation of the so far ill-defined YchF/Ola1 family of proteins and stipulate their role as negative regulators of the oxidative stress response. Antioxid. Redox Signal. 24, 141-156.

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Section: Discussionmentioning

confidence: 99%

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

Hannemann

Suppanz

et al. 2016

Antioxidants & Redox Signaling

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“…DNA damage also induces the phosphorylation of the histone variant H2AX (then called γH2AX), which forms foci at sites of DNA damage, especially double-strand breaks (69) . γH2AX has recently been put forward as a potential candidate biomarker of ageing with clinical potential (70)(71)(72) . The capacity to repair DNA double-strand breaks is impaired with ageing (73)(74)(75) .…”

Section: Some Recent Biomarker Examplesmentioning

confidence: 99%

“…Cell senescence is now known to be mechanistically integrated with inflammation (66) and with oxidative stress (78) . However, so far a few markers of molecular oxidative damage or inflammation appear useful and consistent as biomarkers of ageing in human cohorts (71,79) . A candidate biomarker of ageing should only be regarded as fully validated if it fulfils the requirements stated earlier.…”

Section: Some Recent Biomarker Examplesmentioning

confidence: 99%

Biomarkers of healthy ageing: expectations and validation

Martin-Ruiz

Zglinicki

2014

Proc. Nutr. Soc.

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The challenge of devising a set of biomarkers capable of measuring the ageing rate in human subjects was articulated long ago. In recent years, progress in the basic biology of ageing suggests the realistic possibility of preventive or restaurative interventions that may extend healthy lifespan in mammals including human subjects. Specifically, frailty is being increasingly recognised as a clinically relevant syndrome that may be therapeutically addressed. This greatly enhances the need for sensitive and specific biomarkers of healthy ageing that are validated in both experimental animals and, importantly, in human subjects over the whole age range. Here, we will discuss the present challenges and requirements for biomarker validation in human subjects. We propose the central requirements for a validated biomarker of healthy ageing as: (i) better predictive power than chronological age for multiple dimensions of ageing; (ii) identification of the age range in which the marker is informative; (iii) establishment of sensitivity/specificity as indicators of its predictive power at the level of the individual; (iv) minimisation of methodological variation between laboratories.

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“…"Oxidative stress theory" holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impact on critical aspects of aging process and contribute to impaired physiological function, increased incidence of disease, and a reduction in life span [30,31,33,34].…”

Section: Oxidative Stress and Its Pathophysiological Implication In Amentioning

confidence: 99%

“…Therefore, stress-induced cellular injury appears to be exaggerated with advancing age [33,34].This failure to effectively respond to cellular challenge has been postulated to contribute to a reduction in stress tolerance and the development of various pathologies and diseases. Factors such as these are likely to contribute to the cellular dysfunction and reductions in stress tolerances that are hallmarks of aging [10,39].…”

Section: Integrative Analysismentioning

confidence: 99%

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

Valle¹

2014

Epidemiol

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Metabolic issues persist in HIV patients who are otherwise stable with and without antiretroviral treatment. Metabolic alterations are associated to chronic inflammation, severe mitochondrial toxicity and oxidative stress as critical factors influencing HIV disease outcomes even during antiretroviral treatment. These aspects could also be involved in comorbidities and premature aging. Both factors should be managed during therapy and they should be focus of intense ongoing investigation.The aim of this mini-review is to describe essential mechanisms of in vivo reactive oxygen species generation, antioxidants pathways, and oxidative stress involved in HIV disease. Potential impact on reactive oxygen species, oxidative damage, cellular function, and how these responses change could mediate aging in pathophysiological situations are discussed. Accrual experimental and clinical reports analyses allow us a better understanding of various inter-related contributing factors. In addition, oxidative stress as an often-overlooked link between HIVinfection and the progression of aids, during antiretroviral treatment, is analyzed. Potential long-term consequences of antioxidant treatment require on-going investigation in order to obtain important clinical issues that have recently been reported. Currently, the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors of non-aids-related conditions.

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Markers of oxidant stress that are clinically relevant in aging and age-related disease

Cited by 197 publications

References 259 publications

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

Redox Activation of the Universally Conserved ATPase YchF by Thioredoxin 1

Biomarkers of healthy ageing: expectations and validation

Altered Redox Regulation as Cofactor in Comorbidities and Accelerated Aging in HIV Infection Evolution and Antiretroviral Treatment

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