Dataset Information

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

ABSTRACT: The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial burden of fatty acid oxidation. As a result, if senescence, metabolism, and circadian rhythm are all linked, anti-obesity treatments may improve metabolic regulation while also alleviating senescence and circadian rhythm. Vutiglabridin is a small molecule in clinical trials that improves obesity by enhancing mitochondrial function. We found that chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin alleviates all investigated markers of cellular senescence (SA-β-gal, CDKN1A, CDKN2A) and dysfunctional cellular circadian rhythm (BMAL1) while remarkably preventing the alterations of mitochondrial function and structure that occur during the process of cellular senescence. Our results demonstrate the significant senescence-alleviating effects of vutiglabridin, specifically with the restoration of cellular circadian rhythmicity and metabolic regulation. These data support the potential development of vutiglabridin against aging-associated diseases and corroborate the intricate link between cellular senescence, metabolism, and the circadian clock.

SUBMITTER: Heo JW

PROVIDER: S-EPMC10812742 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

Heo Jin-Woong JW Lee Hye-Eun HE Lee Jimin J Choi Leo Sungwong LS Shin Jaejin J Mun Ji-Young JY Park Hyung-Soon HS Park Sang-Chul SC Nam Chang-Hoon CH

Antioxidants (Basel, Switzerland) 20240116 1

The process of cellular senescence, which is characterized by stable cell cycle arrest, is strongly associated with dysfunctional cellular metabolism and circadian rhythmicity, both of which are reported to result from and also be causal to cellular senescence. As a result, modifying any of them-senescence, metabolism, or the circadian clock-may affect all three simultaneously. Obesity accelerates aging by disrupting the homeostasis of reactive oxygen species (ROS) via an increased mitochondrial ...[more]

PMID: 38247533

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Project description:BackgroundPlant senescence is the process of physiological maturation of plants and is important for crop yield and quality. Senescence is controlled by several factors, such as temperature and photoperiod. However, the molecular basis by which these genes promote senescence in soybeans is not well understood. We identified senescence-related genes via transcriptome analysis of early-senescence (ES)- and late-senescence (LS)-type plants to elucidate the molecular mechanisms of senescence in soybeans.ResultsWe obtained early-senescence (ES)- and late-senescence (LS)-type F7 plants from a cross between a hybrid (Glycine max × Glycine soja) and the Glycine max cultivar. The ES-type plants presented the reproductive (R2) growth stage at 50 days after sowing (DAS) and the R7 growth stage at 95 DAS, whereas the LS-type plants presented the beginning of the R1 and R6 growth stages at 50 and 95 DAS, respectively. To understand the molecular mechanisms underlying this senescence, we performed transcriptome analysis of leaves from 50 to 95 DAS of ES- and LS-type plants. A total of 2,414 and 2,471 genes at 50 and 95 DAS, respectively, were differentially expressed between ES-type and LS-type plants. Twenty-three candidate genes associated with the circadian clock, chlorophyll biosynthesis, phytohormones, and senescence-associated protein kinases were identified, and their expression levels were analyzed. In addition, to understand interaction between circadian clock and senescence, we analyzed expression patterns of seven circadian clock-related genes during the time period (light and dark condition): CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), CONSTANS-LIKE 9 (COL9), LUX ARRHYTHMO (LUX) EARLY FLOWERING 3 (ELF3), PSEUDO-RESPONSE REGULATOR5 (PRR5) and GIGANTEA (GI). The expression patterns of circadian clock-related genes were similar in the ES- and LS-type plants. However, the transcription levels of these genes were compared between ES- and LS-type plants, and the expression of these genes was greater than that in LS-type plants during the period when expression increased. Therefore, each set of candidate genes regulated senescence in each plant by regulating their expression level.ConclusionsThese findings provide novel insights into the regulation of senescence in soybean plants, which could lead to the development of new strategies to improve agriculture.

Dataset Information

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

Publications

Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts.

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