Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal Fibroblasts
0301 basic medicine
570
MITOCHONDRIAL DYSFUNCTION
human dermal fibroblasts
HUMAN-CELLS
BMAL1
610
RM1-950
circadian clocks
Article
MECHANISMS
ACTIVATION
03 medical and health sciences
DNA-DAMAGE
KINASE
cellular senescence
CONNECTIONS
RHYTHM
Therapeutics. Pharmacology
OXIDATIVE STRESS
metabolism
mitochondrial homeostasis
DOI:
10.3390/antiox13010109
Publication Date:
2024-01-16T13:12:37Z
AUTHORS (9)
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.
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CITATIONS (2)
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