The Chemical Exposome of Human Aging

Misra, Biswapriya B.

doi:10.3389/fgene.2020.574936

Cited by 21 publications

(10 citation statements)

References 120 publications

(135 reference statements)

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“…transcription) exhibit inconsistencies in age-related signatures dependent on individual, tissue and cell type. Gene expression signatures in natural aged samples are influenced by numerous factors, including historic exposures to radiation, infectious agents, disease and (bio)chemicals [ 14 , 15 ]. Controlled laboratory studies using representative cell lines and model organisms are commonly used to alleviate historic variability, but carry limitations of the in vitro culture and evolutionary or longevity differences across the typical model species (e.g.…”

Section: Introductionmentioning

confidence: 99%

Translational control in cell ageing: an update

Woodward

Shirokikh

2021

Biochemical Society Transactions

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Cellular ageing is one of the main drivers of organismal ageing and holds keys towards improving the longevity and quality of the extended life. Elucidating mechanisms underlying the emergence of the aged cells as well as their altered responses to the environment will help understanding the evolutionarily defined longevity preferences across species with different strategies of survival. Much is understood about the role of alterations in the DNA, including many epigenetic modifications such as methylation, in relation to the aged cell phenotype. While transcriptomes of the aged cells are beginning to be better-characterised, their translational responses remain under active investigation. Many of the translationally controlled homeostatic pathways are centred around mitigation of DNA damage, cell stress response and regulation of the proliferative potential of the cells, and thus are critical for the aged cell function. Translation profiling-type studies have boosted the opportunities in discovering the function of protein biosynthesis control and are starting to be applied to the aged cells. Here, we provide a summary of the current knowledge about translational mechanisms considered to be commonly altered in the aged cells, including the integrated stress response-, mechanistic target of Rapamycin- and elongation factor 2 kinase-mediated pathways. We enlist and discuss findings of the recent works that use broad profiling-type approaches to investigate the age-related translational pathways. We outline the limitations of the methods and the remaining unknowns in the established ageing-associated translation mechanisms, and flag translational mechanisms with high prospective importance in ageing, for future studies.

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Section: Introductionmentioning

confidence: 99%

Translational control in cell ageing: an update

Woodward

Shirokikh

2021

Biochemical Society Transactions

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“…Skin aging is divided into two types: intrinsic and extrinsic aging. Intrinsic aging is dependent on time; however, extrinsic aging is developed by some external factors such as environmental pollution, severe physical stress, and exposure to UV radiation [ 36 , 37 ]. UV radiation plays a significant role in extrinsic aging, called photoaging.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation

et al. 2022

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Human skin is constructed with many proteins such as collagen and elastin. Collagen and elastin play a key role in providing strength and elasticity to the human skin and body. However, damage to collagen causes various symptoms such as wrinkles and freckles, which suggests that they are important to maintain skin condition. Extrinsic or intrinsic skin aging produces an excess of skin destructive factors such as tumor necrosis factor (TNF)-α, which is a major mediator of the aging process. In aged skin, TNF-α provokes the generation of intracellular ROS (reactive oxygen species). It triggers the excessive secretion of MMP-1, which is a collagen-degrading enzyme that causes the collapse of skin collagen. Therefore, we aimed to search for a natural-product-derived candidate that inhibits the skin damage caused by TNF-α in human dermal fibroblasts. In this study, the protective effect of withagenin A diglucoside (WAD) identified from Withania somnifera against TNF-α-stimulated human dermal fibroblasts is investigated. W. somnifera (Solanaceae), well-known as ‘ashwagandha’, is an Ayurvedic medicinal plant useful for promoting health and longevity. Our experimental results reveal that WAD from W. somnifera suppresses the generation of intercellular ROS. Suppressing intracellular ROS generation inhibits MMP-1 secretion and the collapse of type 1 collagen. The effect of WAD is shown to depend on the inhibition of MAPK phosphorylation, Akt phosphorylation, c-Jun phosphorylation, COX-2 expression, and NF-κB phosphorylation. Further, WAD-depressed expression of the pro-inflammatory cytokines IL-6 and IL-8 triggers various inflammatory reactions in human skin. These findings suggest that WAD has protective effects against skin damage. Accordingly, our study provides experimental evidence that WAD can be a potential agent that can be applied in various industrial fields, such as cosmetics and pharmaceuticals related to skin aging.

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“…The exposome includes both organic and inorganic chemicals (i.e., elements). The exposome refers to chemicals with no known metabolic function in the human body or that are not natural components of human body (pollutants and nonnutritive plant chemicals) ( Misra 2020 ). Analysis of the organic exposome was conducted with ultra-high performance liquid chromatography Ultimate 3000 system (Dionex, Germering, Germany)–Q Exactive hybrid quadrupole-orbitrap high resolution mass spectrometry (UHPLC-QE-HRMS) (Thermo Fisher Scientific), which covered major kinds of bioactive environmental chemicals, including pesticides, antimicrobial agents, phthalates, phenols, phytoestrogens, parabens, food metabolites, smoking metabolites, fire retardants, personal care products, and perfluorochemicals ( CDC 2015 , 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Associations between the Maternal Exposome and Metabolome during Pregnancy

Chen

Guan

Huang

et al. 2022

Environ Health Perspect

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Background: Maternal exposure to environmental chemicals during pregnancy can influence various maternal and offspring health parameters. Modification of maternal metabolism by environmental exposure may be an important pathway for these impacts. However, there is limited evidence regarding exposure to a wide array of chemicals and the metabolome during pregnancy. Objectives: We investigated the relationship between the urinary exposome and metabolome during pregnancy. Methods: Urine samples were collected in the first and third trimesters from 1,024 pregnant women recruited in prenatal clinics in Jiangsu Province, China. The exposome was analyzed using the first trimester sample with ultra-high performance liquid chromatography–high resolution accurate mass spectrometry (UHPLC-HRMS) and inductively coupled plasma mass spectrometry. The metabolome was analyzed using the third trimester sample with UHPLC-HRMS. We evaluated associations between each of 106 exposures in the first trimester with 139 metabolites in the third trimester. Results: We identified 1,245 significant associations ( , Bonferroni correction) between chemical exposures and maternal metabolism during pregnancy. Among elements, the largest number of the significant metabolic associations were observed for magnesium, and among organic compounds, for 4- -octylphenol. We used exposome–metabolome associations to explore mechanisms underlying published associations between prenatal chemical exposures and offspring health outcomes. This integration of the literature with our results suggests that reported associations between 10 analytes and birth weight, gestational age, fat deposition, neurobehavioral development, immunological disorders, and hypertension may be partially mediated by metabolites associated with these exposures. Discussion: This high-dimensional analysis of the urinary exposome and metabolome identified many associations between chemical exposures and maternal metabolism during pregnancy. Integration of these associations with the literature on health outcomes of exposure suggests that environmental modulation of the maternal metabolome may play a role in the association between prenatal exposure on pregnancy and child health outcomes. https://doi.org/10.1289/EHP9745

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The Chemical Exposome of Human Aging

Cited by 21 publications

References 120 publications

Translational control in cell ageing: an update

Translational control in cell ageing: an update

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation

Associations between the Maternal Exposome and Metabolome during Pregnancy

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