Ageing – Oxidative stress, PTMs and disease

Ebert, Thomas; Tran, Ngoc Hieu; Schurgers, Leon J.; Stenvinkel, Peter; Shiels, Paul G.

doi:10.1016/j.mam.2022.101099

Cited by 64 publications

(34 citation statements)

References 105 publications

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“…199 In keeping with this postulate, the derepression of long interspersed nuclear elements with activation via demethylation, drives interferon production in SC and promotes age-associated inflammation. 200 Histone posttranslational modifications have also been reported in CVD, 170 and mirror changes observed with physiological senescence, 201 at or near long interspersed nuclear element arrays.…”

Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning

confidence: 82%

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

Hobson

Arefin

Witasp

et al. 2023

Circulation Research

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The pathophysiology of vascular disease is linked to accelerated biological aging and a combination of genetic, lifestyle, biological, and environmental risk factors. Within the scenario of uncontrolled artery wall aging processes, CKD (chronic kidney disease) stands out as a valid model for detailed structural, functional, and molecular studies of this process. The cardiorenal syndrome relates to the detrimental bidirectional interplay between the kidney and the cardiovascular system. In addition to established risk factors, this group of patients is subjected to a plethora of other emerging vascular risk factors, such as inflammation, oxidative stress, mitochondrial dysfunction, vitamin K deficiency, cellular senescence, somatic mutations, epigenetic modifications, and increased apoptosis. A better understanding of the molecular mechanisms through which the uremic milieu triggers and maintains early vascular aging processes, has provided important new clues on inflammatory pathways and emerging risk factors alike, and to the altered behavior of cells in the arterial wall. Advances in the understanding of the biology of uremic early vascular aging opens avenues to novel pharmacological and nutritional therapeutic interventions. Such strategies hold promise to improve future prevention and treatment of early vascular aging not only in CKD but also in the elderly general population.

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Section: Compendium On Increased Risk Of Cardiovascular Complications...mentioning

confidence: 82%

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

Hobson

Arefin

Witasp

et al. 2023

Circulation Research

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“…However, the high caries prevalence alongside the potential risk of harm for the patients on RRT supports a demand for improved oral care in those individuals. In the context of the interrelation between oral conditions and kidney failure, several different factors appear of relevance: thereby, those patients are a special cohort with different systemic conspicuities, including increased levels of oxidative stress and inflammation [ 56 ], alongside premature ageing of the whole body and vascular system [ 57 , 58 ]. Those issues could be influential for the high oral burden in those individuals, and vice versa.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Dental Caries in Patients on Renal Replacement Therapy—A Systematic Review

Kreher

Ernst

Ziebolz

et al. 2023

JCM

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Patients under renal replacement therapy (RRT) often show oral problems, including dry mouth, periodontal and dental diseases. This systematic review aimed to evaluate the caries burden in patients on RRT. Therefore, a systematic literature search based on the databases PubMed, Web of Science and Scopus was performed by two independent individuals in August 2022. Search terms were: “caries” AND “dialysis”, “caries” AND “renal replacement therapy”, “caries” AND “kidney”. The systematic process was complemented by manual search. Studies on adult patients (age ≥ 18 years), treated by any form of RRT and explicitly reporting caries prevalence or incidence were checked for their eligibility and subsequently analyzed qualitatively. For all included studies, a quality appraisal was applied. From the systematic search, 653 studies were identified, of which 33 clinical investigations were included in the qualitative analysis. The majority (31 studies) of all included patients underwent hemodialysis (HD), with a sample size between 28 and 512 participants. Eleven studies investigated a healthy control group. Oral examinations were heterogeneous across studies; the caries burden was primarily assessed by decayed-(D-T), missing- and filled-teeth index (DMF-T). The number of decayed teeth ranged between 0.7 and 3.87 across studies. Only six out of these 11 studies found significant differences in caries prevalence/incidence between RRT and controls, whereby only four studies confirmed worse caries burden in RRT individuals. No information was provided on caries stadium (initial caries, advanced caries, invasive treatment need), caries activity or location (e.g., root caries) across studies. Most of the included studies were assessed to be of moderate quality. In conclusion, patients on RRT suffer from a high prevalence of dental caries. Alongside a need for further research in the field, improved, multidisciplinary, patient-centered dental care concepts are required to support dental and overall oral health in individuals on RRT.

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“…In case of murzymes like CYPs, however, quests for mechanism based inactivation strategies to influence select CYPs did not give fruitful search outcomes (Ortiz de Montellano, 2015). Several PTM-based strategies (particularly, in the context of the most usual PTMs of phosphorylation and acylation) have been approved by FDA, to address diseases and aging related issues (Ebert et al, 2022). Strategies involving specific PTMs have been proposed as counter-measures, eg.…”

Section: B Lysine-acylationmentioning

confidence: 99%

Murburn modifications of proteins

Manoj¹

2022

Preprint

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Murburn concept constitutes the thesis that diffusible reactive species or (DRS) are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn post-translational modifications (PTMs) result because murburn/murzyme functionalism is integral to cellular existence, which must incorporate the inherently stochastic nature of operations mediated by DRS. Due to the earlier/inertial stigmatic perception that DRS are mere agents of chaos, several such outcomes were either understood as deterministic modulations sponsored by house-keeping enzymes or deemed as unregulated non-enzymatic events resulting out of ‘oxidative stress’. In the current review, I dispel the myths around DRS-functions, and undertake systematic parsing and analyses of murburn modifications of proteins. Although it is impossible to demarcate all PTMs into the classical or murburn modalities, telltale signs of the latter are evident from the relative inaccessibility of the locus, non-specificities and mechanistic details. It is pointed out that while many murburn PTMs may be harmless, some others could have deleterious or beneficial physiological implications. Some details of reversible/irreversible modifications of amino acid residues and cofactors that may be subjected to phosphorylation, halogenation, glycosylation, alkylation/acetylation, hydroxylation/oxidation, etc. are listed, along with citations of select proteins where such modifications have been reported. The contexts of these modifications and their significance in (patho)physiology/aging and therapy are also presented. With more balanced explorations and statistically verified data, a definitive understanding of normal versus pathological contexts of murburn modifications would be obtainable in the future.

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Ageing – Oxidative stress, PTMs and disease

Cited by 64 publications

References 105 publications

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

Accelerated Vascular Aging in Chronic Kidney Disease: The Potential for Novel Therapies

Prevalence of Dental Caries in Patients on Renal Replacement Therapy—A Systematic Review

Murburn modifications of proteins

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