The Drivers of Cellular Senescence

Previous Science Note

Cellular senescence is a complex biological process that is influenced by several key factors: DNA damage, telomere shortening, oxidative stress, oncogene activation, and so on. These factors collectively contribute to the complex process of cellular senescence, which acts as a double-edged sword - protective in preventing cancer growth, but also contributing to aging and age-related diseases.

Apoptotic stress causes mtDNA release during senescence and drives the SASP
Click here for the original article: Stella Victorelli, et. al., Nature, 2023.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype
Click here for the original article: Mate Maus, et. al., Nature, 2023.
Genome-wide CRISPR activation screening in senescent cells reveals SOX5 as a driver and therapeutic target of rejuvenation
Click here for the original article: Yaobin Jing, et. al., Cell Stem Cell, 2023.

Point of Interest
- Some mitochondrial outer membrane permeabilization (MOMP) requires BAX and BAK macropores.
- These macropores allow the release of mitochondrial DNA (mtDNA) into the cytosol.
- Cytosolic mtDNA in turn activates the cGAS-STING pathway, a key regulator of the SASP.  
- Inhibition of MOMP in vivo reduces inflammatory markers and improves healthspan in aged mice.
 

Point of Interest
- Vascular and hemolytic injury trigger iron accumulation, which causes senescence and promotes fibrosis.
- Senescent cells persistently accumulate iron, even after the increase in extracellular iron has subsided.
- Cells exposed to various types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes.
- The high levels of labile iron fuel the generation of reactive oxygen species and the SASP.  
Point of Interest
- CRISPRa screening identifies a comprehensive set of rejuvenators against senescence.
- Activation of SOX5 initiates a rejuvenation program via epigenetic remodeling.
- SOX5 activation leads to the stimulation of the HMGB2 enhancer, resulting in subsequent geroprotective effects. 
- Gene therapy using only SOX5 has the potential to promote the regeneration of aged knee joints.
Related Techniques
           Cellular senescence detection SPiDER-βGal for live-cell imaging or flow cytometry / microplate reader / tissue samples.
           Ferrous ion (Fe2+) detection FerroOrange and Mito-FerroGreen
           Total ROS detection Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA
           Lysosomal function Lysosomal Acidic pH Detection Kit-Green/Red and Green/Deep Red
           Mitochondrial superoxide detection MitoBright ROS Deep Red - Mitochondrial Superoxide Detection
           Mitochondrial membrane potential detection JC-1 MitoMP Detection Kit / MT-1 MitoMP Detection Kit
           Oxygen consumption rate assay Extracellular OCR Plate Assay Kit
           Antibody/Protein labeling: quick and high recovery Fluorescein, Biotin, and Peroxidase Labeling Kit - NH2
Related Applications

Metabolic shift to glycolysis in senescenct cells

       

 

NAD(+) levels decline during the aging process, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies*. Here, we try to redemonstrate this phenomenon in the doxorubicin (DOX)-induced cellular senescence model with a comprehensive analysis of our products.

*S. Imai, et al., Trends Cell Biol, 2014, 24, 464-471


Products in Use
① DNA Damage Detection Kit - γH2AX
② Cellular Senescence Detection Kit - SPiDER-βGal
 NAD/NADH Assay Kit-WST
④ JC-1 MitoMP Detection Kit
⑤ Glycolysis/OXPHOS Assay KitLactate Assay Kit-WST

 

 


 

Product Classification

Product Classification