Related Experiment Video

Updated: Nov 29, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

8.4K

Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression

Chae Young Hwang1, Ying-Hao Han1, Seung-Min Lee1

  • 1Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

Annals of Geriatric Medicine and Research
|November 23, 2020
PubMed
Abstract

Insights

Sestrin2 (Sesn2) protein protects against cellular senescence by reducing reactive oxygen species via the TGF-β and NOX4 pathways, thereby maintaining metabolic homeostasis.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Aging research

Background:

  • Sestrin2 (Sesn2) plays a role in metabolic homeostasis and aging.
  • It modulates the 5' AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) pathway.

Purpose of the Study:

  • To investigate the role of Sestrin2 in cellular senescence.
  • To elucidate the molecular mechanisms underlying Sesn2's function in preventing senescence.

Main Methods:

  • Utilized wild-type and Sesn2 knockout (KO) mice and their derived mouse embryonic fibroblasts (MEFs).
  • Assessed cellular morphology, senescence-associated β-galactosidase activity, and reactive oxygen species (ROS) levels.
  • Investigated the expression of NADPH oxidase 4 (NOX4) and transforming growth factor-β (TGF-β).
  • Examined the effects of NOX and TGF-β inhibitors on Sesn2-KO MEFs.

Main Results:

  • Sesn2-KO MEFs exhibited enlarged, flattened morphology and increased senescence markers.
  • Elevated reactive oxygen species (ROS) levels were observed in Sesn2-KO MEFs, which were reversed by N-acetyl-cysteine.
  • Increased mRNA levels of NOX4 and TGF-β were detected in Sesn2-KO MEFs.
  • Inhibitors of NOX4 and TGF-β restored cell growth in Sesn2-KO MEFs.

Conclusions:

  • Sestrin2 (Sesn2) attenuates cellular senescence.
  • Sesn2 functions by suppressing TGF-β- and NOX4-induced ROS generation.
  • This suppression subsequently inhibits AMPK, contributing to the prevention of senescence.
Keywords:
Reactive oxygen speciesSenescenceSestrin2NOX4

More Related Videos

Techniques to Induce and Quantify Cellular Senescence06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

34.5K
Induction and Validation of Cellular Senescence in Primary Human Cells08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

17.6K

Related Concept Videos

Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.1K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
17.3K
Meiosis II02:02

Meiosis II

Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
48.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.6K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.7K