Comparative Blood and Urine Metabolomics Analysis of Healthy Elderly and Young Male Singaporeans

Chen, Liwei; Zhang, Jingtao; Teh, Jean Pui Yi; Cheon, Bobby K.; Yang, Yifan; Schlundt, Jørgen; Wang, Yulan; Conway, Patricia L.

doi:10.1021/acs.jproteome.0c00215

Cited by 18 publications

(15 citation statements)

References 58 publications

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“…3 B, was primarily detected in urine samples of humans 23 , 24 and was not detected robustly (raw count > 1,000; see “ Materials and methods ”) in our previously analyzed metabolomic datasets 22 . Furthermore, Chen et al 25 demonstrated that serum deoxythreonate levels correlate with age of blood donors. We are not aware of the ages of the donors for the independent experiments performed under untreated and drug-treated conditions, but historically the age of the donors for our blood-collection protocol has been between 18 and 60 years.…”

Section: Resultsmentioning

confidence: 99%

Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure

Tewari

Kwan

Elahi

et al. 2022

Sci Rep

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Due to the recurring loss of antimalarial drugs to resistance, there is a need for novel targets, drugs, and combination therapies to ensure the availability of current and future countermeasures. Pyrazoleamides belong to a novel class of antimalarial drugs that disrupt sodium ion homeostasis, although the exact consequences of this disruption in Plasmodium falciparum remain under investigation. In vitro experiments demonstrated that parasites carrying mutations in the metabolic enzyme PfATP4 develop resistance to pyrazoleamide compounds. However, the underlying mechanisms that allow mutant parasites to evade pyrazoleamide treatment are unclear. Here, we first performed experiments to identify the sublethal dose of a pyrazoleamide compound (PA21A092) that caused a significant reduction in growth over one intraerythrocytic developmental cycle (IDC). At this drug concentration, we collected transcriptomic and metabolomic data at multiple time points during the IDC to quantify gene- and metabolite-level alterations in the treated parasites. To probe the effects of pyrazoleamide treatment on parasite metabolism, we coupled the time-resolved omics data with a metabolic network model of P. falciparum. We found that the drug-treated parasites adjusted carbohydrate metabolism to enhance synthesis of myoinositol—a precursor for phosphatidylinositol biosynthesis. This metabolic adaptation caused a decrease in metabolite flux through the pentose phosphate pathway, causing a decreased rate of RNA synthesis and an increase in oxidative stress. Our model analyses suggest that downstream consequences of enhanced myoinositol synthesis may underlie adjustments that could lead to resistance emergence in P. falciparum exposed to a sublethal dose of a pyrazoleamide drug.

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Section: Resultsmentioning

confidence: 99%

Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure

Tewari

Kwan

Elahi

et al. 2022

Sci Rep

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“…Additionally, we related our findings with previously identified metabolites in serum and urine metabolome profiles from the same subjects. 74 Herein, we examined the common key metabolites with significant differences in concentration between the two age groups in the serum (or urine) and intestinal tract. One major finding is the consistent decrease in branched-chain amino acids (BCAAs: valine, leucine, isoleucine) in the gut and serum metabolome of elderly individuals, in accordance with some previous studies showing that BCAAs have a beneficial effect on aging.…”

Section: Discussionmentioning

confidence: 99%

“…The study participants and methods of sample collection have been reported previously. 80 Briefly, 32 healthy young (age, 23.1 ± 1.4 years) and 30 generally healthy elderly (age, 69.0 ± 3.5 years) Chinese male Singaporeans were recruited. Dietary records (2 weekdays and 1 weekend) were analyzed using a curated in-house database that was compiled from various online sources and nutrition labels (See Supplementary Table S13).…”

Section: Methodsmentioning

confidence: 99%

Integrative multiomics analysis reveals host-microbe-metabolite interplays associated with the aging process in Singaporeans

et al. 2022

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The age-associated alterations in microbiomes vary across populations due to the influence of genetics and lifestyles. To the best of our knowledge, the microbial changes associated with aging have not yet been investigated in Singapore adults. We conducted shotgun metagenomic sequencing of fecal and saliva samples, as well as fecal metabolomics to characterize the gut and oral microbial communities of 62 healthy adult male Singaporeans, including 32 young subjects (age, 23.1 ± 1.4 years) and 30 elderly subjects (age, 69.0 ± 3.5 years). We identified 8 gut and 13 oral species that were differentially abundant in elderly compared to young subjects. By combining the gut and oral microbiomes, 25 age-associated oral-gut species connections were identified. Moreover, oral bacteria Acidaminococcus intestine and Flavonifractor plautii were less prevalent/abundant in elderly gut samples than in young gut samples, whereas Collinsella aerofaciens and Roseburia hominis showed the opposite trends. These results indicate the varied gut-oral communications with aging. Subsequently, we expanded the association studies on microbiome, metabolome and host phenotypic parameters. In particular, Eubacterium eligens increased in elderly compared to young subjects, and was positively correlated with triglycerides, which implies that the potential role of E. eligens in lipid metabolism is altered during the aging process. Our results demonstrated aging-associated changes in the gut and oral microbiomes, as well as the connections between metabolites and host-microbe interactions, thereby deepening the understanding of alterations in the human microbiome during the aging process in a Singapore population.

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“…Shen et al. further extended the use of the DFFP‐containing design by introducing a small peptide substrate sequence for PTP1B as well as the nonhydrolyzable pTyr mimic known as F 2 PmP ( 32 , Figure ) . The resulting ABP was shown to be more selective for PTP1B compared to PTP4A3.…”

Section: Global Analysis Of Pp Activitymentioning

confidence: 99%

Interrogating Protein Phosphatases with Chemical Activity Probes

Casey

Stains

2018

Chemistry A European J

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Protein phosphatases, while long overlooked, have recently become appreciated as drivers of both normal- and disease-associated signaling events. As a result, the spotlight is now turning torwards this enzyme family and efforts geared towards the development of modern chemical tools for studying these enzymes are well underway. This Minireview focuses on the evolution of chemical activity probes, both optical and covalent, for the study of protein phosphatases. Small-molecule probes, global monitoring of phosphatase activity through the use of covalent modifiers, and targeted fluorescence-based activity probes are discussed. We conclude with an overview of open questions in the field and highlight the potential impact of chemical tools for studying protein phosphatases.

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Comparative Blood and Urine Metabolomics Analysis of Healthy Elderly and Young Male Singaporeans

Abstract: Comparative blood and urine metabolomics analysis of healthy elderly and young male Singaporeans

Cited by 18 publications

References 58 publications

Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure

Metabolic adjustments of blood-stage Plasmodium falciparum in response to sublethal pyrazoleamide exposure

Integrative multiomics analysis reveals host-microbe-metabolite interplays associated with the aging process in Singaporeans

Interrogating Protein Phosphatases with Chemical Activity Probes

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