Related Experiment Video
Updated: Jul 5, 2025

Induction and Validation of Cellular Senescence in Primary Human Cells
Published on: June 20, 2018
Vutiglabridin Alleviates Cellular Senescence with Metabolic Regulation and Circadian Clock in Human Dermal
Jin-Woong Heo1,2, Hye-Eun Lee3,4, Jimin Lee1
1School of Undergraduate Studies, Daegu Gyeongbuk Institute of Science and Technology, College of Transdisciplinary Studies, Daegu 42988, Republic of Korea.
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.
Insights
Vutiglabridin alleviates cellular senescence and restores circadian rhythm by improving mitochondrial function. This anti-obesity compound shows promise for treating aging-associated diseases by targeting the link between senescence, metabolism, and the circadian clock.
Area of Science:
- Gerontology
- Cell Biology
- Metabolomics
Background:
- Cellular senescence, marked by cell cycle arrest, is linked to metabolic dysfunction and disrupted circadian rhythms.
- Obesity exacerbates aging by increasing oxidative stress and mitochondrial burden, impacting these interconnected processes.
- Vutiglabridin, an anti-obesity molecule, enhances mitochondrial function.
Purpose of the Study:
- To investigate the effects of vutiglabridin on cellular senescence, metabolism, and circadian rhythm.
- To determine if vutiglabridin can alleviate senescence markers and restore circadian clock function.
- To explore the therapeutic potential of vutiglabridin in aging-associated diseases.
Main Methods:
- Chronic treatment of senescent primary human dermal fibroblasts (HDFs) with vutiglabridin.
- Assessment of senescence markers (SA-β-gal, CDKN1A, CDKN2A).
- Evaluation of circadian rhythm markers (BMAL1) and mitochondrial function/structure.
Main Results:
- Vutiglabridin treatment reduced key markers of cellular senescence.
- The compound restored the dysfunctional cellular circadian rhythm (BMAL1).
- Vutiglabridin prevented mitochondrial alterations associated with senescence and improved metabolic regulation.
Conclusions:
- Vutiglabridin demonstrates significant senescence-alleviating effects.
- The drug restores cellular circadian rhythmicity and metabolic regulation.
- These findings support vutiglabridin's potential for aging-associated diseases, highlighting the senescence-metabolism-circadian clock link.
Related Concept Videos
Replicative Cell Senescence
Circadian Rhythms and Gene Regulation
Renewal of Skin Epidermal Stem Cells
Tissue Renewal without Stem Cells
However, failure of such a system...
The Cell Cycle Control System
Mitochondria

