Proteome Oxidative Modifications and Impairment of Specific Metabolic Pathways During Cellular Senescence and Aging

Hamon, Marie-Paule; Ahmed, Emad K.; Baraibar, Martín A.; Friguet, Bertrand

doi:10.1002/pmic.201800421

Cited by 16 publications

(11 citation statements)

References 45 publications

(77 reference statements)

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“…After years of research, researchers have put forward many hypotheses about aging mechanism, such as oxidative stress, genetic determination theory, free radical theory, neuroendocrine theory, mitochondrial damage theory, etc. [4,6,7]. Most importantly, increasing oxidative stress, a major characteristic of aging, has been implicated in various age-related diseases [8].…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

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Background Aging represents the main risk factor for a number of debilitating diseases and contributes to increase in mortality. Previous studies have shown that ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. In this study, we proposed a network pharmacology-based method to identify the therapeutic pathways of EGb for aging.Methods The active components of EGb and targets of sample chemicals were obtained from TCMSP database. Aging-related genes were obtained by retrieving the Human Ageing Genomic Resources database and the JenAge Ageing Factor Database. Then, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was built, which was used to investigate pharmacological mechanisms of EGb for Aging.Results 24 active components, 154 targets of active components of EGb and 308 targets of aging were obtained. Network construction and pathway enrichment were carried out after data integration. The research found that flavonoids (quercetin, luteolin, kaempferol) and beta-sitosterol might be the main active component of EGb. The top eight candidate targets, including PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, ESR1, were chosen as EGb’s main therapeutic targets. The results of pathway enrichment participated in various pathways associated with inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance and regulating cellular biological processes, etc. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol and PTGS2 had better binding capacity with kaempferol and quercetin.Conclusions The main components of EGb might act on multiple targets, such as PTGS2, PPARG, DPP4, GSK3B, etc., to regulate multiple pathways and played an anti- aging role by inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Liu

Zhang

et al. 2020

Preprint

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“…Among them, the irreversible oxidative modifications of proteins are becoming more and more prominent in key cellular pathways and the pathogenesis of age-related diseases [151,152].…”

Section: Discussionmentioning

confidence: 99%

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

Liu

Pan

Hua

et al. 2020

Preprint

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Aging is an inevitable course of life. Additionally, the risk of chronic diseases or cancer increases with age. The comprehensive identification of signs related to aging can be beneficial for the prevention and early diagnosis of geriatric diseases. The comparison of global modifications in the urine proteome is a means of multidimensional information mining. This approach is based on urine, in which changes from whole-body metabolism can accumulate. This study used the urine of healthy people at different ages (22 children, 10 young people, 6 senior people) as the research object and using high-resolution tandem mass spectrometry, label-free quantitation combined with non-limiting modification identification algorithms and random group test, compared the differences in protein chemical modifications among three groups. The results show that multi-sites oxidative modifications and amino acid substitutions are noticeable features that distinguish these three age groups of people. The proportion of multi-site oxidations in urine proteins of senior (29.76%) is significantly higher than the young group (13.71% and 12.97%), which affect the biological processes of various proteins. This study could provide a reference for studies of aging mechanisms and biomarkers of age-related disease.

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“…In view of the complexity in redox‐mediated signaling pathways involved in senescence, redox proteomics would be the ideal approach to identify redox modified proteins. Interestingly supporting the role for oxidants in the regulation of signaling pathways during the establishment of senescence, it was shown that proteins targeted for oxidative modification in human fibroblasts undergoing replicative senescence fall into three main categories: energy metabolism, quality control‐stress response, and cytoskeleton organization . Similarly, data obtained through comparison of brain regions from senescent rats (28 months) with adult rats (12 months) by redox proteomics have identified oxidatively modified proteins that are involved in energy metabolism, cell structure, signal transduction, and the cellular stress response .…”

Section: Proteomic and Oxidants And Senescencementioning

confidence: 93%

“…Interestingly supporting the role for oxidants in the regulation of signaling pathways during the establishment of senescence, it was shown that proteins targeted for oxidative modification in human fibroblasts undergoing replicative senescence fall into three main categories: energy metabolism, quality control-stress response, and cytoskeleton organization. [142] Similarly, data obtained through comparison of brain regions from senescent rats (28 months) with adult rats (12 months) by redox proteomics have identified oxidatively modified proteins that are involved in energy metabolism, cell structure, signal transduction, and the cellular stress response. [143] More recently, a study on adipocyte mitochondrial proteome has unveiled increased Cysteine oxidation and decreased protein abundance in aging and Type II diabetes conditions.…”

Section: Proteomic and Oxidants And Senescencementioning

confidence: 99%

Organismal Aging and Oxidants beyond Macromolecules Damage

Clément

Luo

2020

Proteomics

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The relationship between oxidants and organismal aging was first articulated through the free radical theory of aging. One of the major predictions of the free radical theory of aging is that oxidative stress shortens organisms’ lifespan because of an increased level of oxidants, which are damaging to macromolecules. However, challenging the role of oxidants in age‐related diseases, there is now sufficient evidence that antioxidant supplements do not provide significant health benefits. Interestingly, in addition to an increase in oxidant‐mediated macromolecules damage, there is convincing experimental data to support the role of senescent cells in the process of aging. Here, the current knowledge regarding the role of oxidants and cellular senescence in organismal aging is reviewed and it is proposed that, in addition to the role of oxidants as inducers of macromolecular damage, oxidants may also function as regulators of signaling pathways involved in the establishment of cellular senescence. If this role for oxidants is established, it may be necessary to modify the free radical theory of aging from “Organisms age because cells accumulate reactive oxygen species‐dependent damage over time” to: “Organisms age because cells accumulate oxidants’‐dependent damage and oxidants’‐dependent senescent characteristics over time.”

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Proteome Oxidative Modifications and Impairment of Specific Metabolic Pathways During Cellular Senescence and Aging

Cited by 16 publications

References 45 publications

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Oxidations and amino acid substitutions in urinary proteins are the distinguishing characteristics of aging

Organismal Aging and Oxidants beyond Macromolecules Damage

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