Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies

Chak, Choiwai Maggie; Lacruz, María Elena; Adam, Jonathan; Brandmaier, Stefan; Covic, M; Huang, Jialing; Meisinger, Christa; Tiller, Daniel; Prehn, Cornelia; Adamski, Jerzy; Berger, Ursula; Gieger, Christian; Peters, Annette; Kluttig, Alexander; Wang-Sattler, Rui

doi:10.3390/metabo9030044

Cited by 42 publications

(46 citation statements)

References 48 publications

(85 reference statements)

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“…Second, our study is cross‐sectional by design which limits its statistical power due to inter‐individual variability of metabolic profiles. To circumvent this issue, two recent studies profiled metabolites in a longitudinal fashion (Chak et al, ; Darst et al, ). Even though these studies improve the robustness of the findings, they do not give insights into mechanisms resulting in the observed metabolic changes.…”

Section: Discussionmentioning

confidence: 99%

Global metabolic profiling to model biological processes of aging in twins

et al. 2019

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Aging is intimately linked to system‐wide metabolic changes that can be captured in blood. Understanding biological processes of aging in humans could help maintain a healthy aging trajectory and promote longevity. We performed untargeted plasma metabolomics quantifying 770 metabolites on a cross‐sectional cohort of 268 healthy individuals including 125 twin pairs covering human lifespan (from 6 months to 82 years). Unsupervised clustering of metabolic profiles revealed 6 main aging trajectories throughout life that were associated with key metabolic pathways such as progestin steroids, xanthine metabolism, and long‐chain fatty acids. A random forest (RF) model was successful to predict age in adult subjects (≥16 years) using 52 metabolites (R2 = .97). Another RF model selected 54 metabolites to classify pediatric and adult participants (out‐of‐bag error = 8.58%). These RF models in combination with correlation network analysis were used to explore biological processes of healthy aging. The models highlighted established metabolites, like steroids, amino acids, and free fatty acids as well as novel metabolites and pathways. Finally, we show that metabolic profiles of twins become more dissimilar with age which provides insights into nongenetic age‐related variability in metabolic profiles in response to environmental exposure.

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Section: Discussionmentioning

confidence: 99%

Global metabolic profiling to model biological processes of aging in twins

et al. 2019

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“…Neopterin, a marker of cellular immune Age related changes in urinary protein excretion. Several metabolites are linked to the ageing process (71) Age group eligibility criteria Balance in age distribution between cases and controls Co-variant analysis (42)…”

Section: Urinary Proteins and Peptidesmentioning

confidence: 99%

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

et al. 2020

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Endometrial cancer is the most common malignancy of the female genital tract and its incidence is rising in parallel with the mounting prevalence of obesity. Early diagnosis has great potential to improve outcomes as treatment can be curative, especially for early stage disease. Current tests and procedures for diagnosis are limited by insufficient accuracy in some and unacceptable levels of invasiveness and discomfort in others. There has, therefore, been a growing interest in the search for sensitive and specific biomarkers for endometrial cancer detection based on non-invasive sampling methodologies. Urine, the prototype non-invasive sample, is attractive for biomarker discovery as it is easily accessible and can be collected repeatedly and in quantity. Identification of urinary biomarkers for endometrial cancer detection relies on the excretion of systemic biomarkers by the kidneys or urinary contamination by biomarkers shed from the uterus. In this review, we present the current standing of the search for endometrial cancer urinary biomarkers based on cytology, genomic, transcriptomic, proteomic, and metabolomic platforms. We summarize the biomarker candidates and highlight the challenges inherent in urinary biomarker discovery. We review the various technologies with promise for biomarker detection and assess these novel approaches for endometrial cancer biomarker research.

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“…The most recent human metabolomic analysis demonstrated that serum L-tyrosine level is upregulated during aging [400,401], and its downregulation is an indicator of CR in humans [402,403]. However, the potential mechanisms for an association between reduced serum levels of L-tyrosine and improvement in metabolic dysfunctions during CR remain unclear.…”

Section: Cisand Trans-rsv Have Opposite Effects On Tyrrs-regulated Pamentioning

confidence: 99%

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

2020

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Unlike widely perceived, resveratrol (RSV) decreased the average lifespan and extended only the replicative lifespan in yeast. Similarly, although not widely discussed, RSV is also known to evoke neurite degeneration, kidney toxicity, atherosclerosis, premature senescence, and genotoxicity through yet unknown mechanisms. Nevertheless, in vivo animal models of diseases and human clinical trials demonstrate inconsistent protective and beneficial effects. Therefore, the mechanism of action of RSV that elicits beneficial effects remains an enigma. In a previously published work, we demonstrated structural similarities between RSV and tyrosine amino acid. RSV acts as a tyrosine antagonist and competes with it to bind to human tyrosyl-tRNA synthetase (TyrRS). Interestingly, although both isomers of RSV bind to TyrRS, only the cis-isomer evokes a unique structural change at the active site to promote its interaction with poly-ADPribose polymerase 1 (PARP1), a major determinant of cellular NAD +-dependent stress response. However, retention of trans-RSV in the active site of TyrRS mimics its tyrosine-bound conformation that inhibits the autopoly-ADP-ribos(PAR)ylation of PARP1. Therefore, we proposed that cis-RSV-induced TyrRS-regulated auto-PARylation of PARP1 would contribute, at least in part, to the reported health benefits of RSV through the induction of protective stress response. This observation suggested that trans-RSV would inhibit TyrRS/PARP1mediated protective stress response and would instead elicit an opposite effect compared to cis-RSV. Interestingly, most recent studies also confirmed the conversion of trans-RSV and its metabolites to cis-RSV in the physiological context. Therefore, the finding that cis-RSV and trans-RSV induce two distinct conformations of TyrRS with opposite effects on the auto-PARylation of PARP1 provides a potential molecular basis for the observed dichotomic effects of RSV under different experimental paradigms. However, the fact that natural RSV exists as a diastereomeric mixture of its cis and trans isomers and cis-RSV is also a physiologically relevant isoform has not yet gained much scientific attention. Keywords Resveratrol (RSV). Aminoacyl-tRNA synthetases (aaRSs). Tyrosyl-tRNA synthetase (YARS. TyrRS). Nicotinamide adenine nucleotide (NAD +). Poly-ADP-ribose polymerase (PARP). Sirtuins (SIRT). AMP-activated protein kinase (AMPK). Nicotinamide (NAM) GeroScience

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Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies

Cited by 42 publications

References 48 publications

Global metabolic profiling to model biological processes of aging in twins

Global metabolic profiling to model biological processes of aging in twins

Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

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