Science Note: The Drivers of Cellular Senescence

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.

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.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype
Click here for the original article: Mate Maus, et. al., Nature, 2023.

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.  

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
- 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 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
③ NAD/NADH Assay Kit-WST
④ JC-1 MitoMP Detection Kit
⑤ Glycolysis/OXPHOS Assay Kit、Lactate Assay Kit-WST
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

What is Cellular Senescence?

 Cellular senescence was reported by Hayflick in 1981. It was discovered when pulmonary fibroblasts slowed down their proliferation and eventually ended in cell death after cell passaging had been performed for more than 8 months. Subsequent studies have revealed that cellular senescence is caused not only by telomere length reduction, but also by external factors such as oncogene activation, oxidative stress, and DNA damage.
The induction and control mechanisms of cellular senescence – in which genetic and external factors are intricately involved – have yet to be fully elucidated. However, it has been suggested that the process is closely related to cancer and various age-related diseases, inspiring large amounts of active research into the topic. The development of drugs that eliminate senescent cells in the body (senolytic drugs) is also attracting the attention of researchers as a possible strategy to extend healthy life expectancy.

Assessing Cellular Senescence

 Cellular senescence is controlled by various factors such as cell type and physiological conditions, such as oxidative stress. None of the individual biomarkers that have been identified so far have been deemed to be specific to senescent cells. Therefore, it is desirable to determine and confirm cellular senescence using multiple indicators.
 Common detection indicators for assessing cellular senescence include features related to cell cycle progression (DNA synthesis, p16/p21 expression, etc.), features related to morphology (of the cell, nucleus, nucleolus, etc.), SA-ß-Gal activity, DNA damage, oxidative stress (ROS), telomere length, inflammatory cytokines (senescence-associated secretory phenotype (SASP)), and more.

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