Are Interleukin Therapies the Future of Anti-Aging?

Previous Science Note

Chronic inflammation drives immune decline and age-related diseases, creating a vicious cycle with senescence. This week, we  introduce a review of the link between senescence and inflammation, along with recent discoveries.

Cellular senescence and inflammation are linked, as senescent cells secrete pro-inflammatory factors that perpetuate chronic inflammation and tissue dysfunction. Chronic inflammation drives immune decline and age-related diseases, creating a vicious cycle with senescence. In this note, we introduce a review article of the link between senescence and inflammation, along with recent findings on anti-IL-17 and anti-IL-11 treatment for anti-senescence. Anti-IL-17 drugs are already approved, and anti-IL-11 therapy is in trials for fibrotic lung disease, suggesting that these treatments may soon help delay aging.

 Review Article   Inflammation and aging: signaling pathways and intervention therapies
Click here for the original article: Xia Li, et. al., Signal Transduct Target Ther., 2023.

Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
Click here for the original article: Anissa A. Widjaja, et. al., Nature, 2024.

Targeting lymphoid-derived IL-17 signaling to delay skin aging
Click here for the original article: Paloma Solá, et. al., Nature Aging, 2024.

Point of Interest
- Chronic inflammation drives aging by promoting cellular senescence, immune dysfunction, and organ damage leading to age-related diseases.

- Inflammaging creates a vicious cycle of inflammation and senescence, suggesting the elimination of inflammation as a potential anti-aging strategy.

- The paper reviews inflammaging, aging models, single-cell technologies, and anti-aging strategies to combat disease and improve quality of life.

Point of Interest
- IL-11 promotes aging by regulating the ERK-AMPK-mTORC1 axis, leading to age-related diseases and reduced lifespan.

- Genetic deletion of IL-11 or use of anti-IL-11 improves metabolism, reduces frailty and extends lifespan by over 20% in mice.

- Anti-IL-11 therapy, currently in clinical trials for fibroinflammatory diseases, may extend health and lifespan in humans with promising safety.
 

Point of Interest
- Skin aging involves structural and functional changes driven by a pro-inflammatory microenvironment and stem cell-intrinsic alterations.

- Single-cell RNA sequencing reveals increased IL-17 signaling in aged skin, which drives inflammation and impairs homeostasis.

- Blocking IL-17 signaling reduces skin inflammation and delays age-related features, suggesting a potential anti-aging skin therapy.

Related Techniques
           Cellular senescence detection SPiDER-βGal for live-cell imaging or flow cytometry / microplate reader / tissue samples
NEW SPiDER-βGal Blue for fixed cell and for multiple staining with immunostaining and other methods
           Oxygen Consumption Rate(OCR) Plate Assay Extracellular OCR Plate Assay Kit
           Total ROS detection Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA
           Glycolysis/Oxidative phosphorylation Assay Glycolysis/OXPHOS Assay Kit
           First-time autophagy research Autophagic Flux Assay Kit
           Lysosomal function Lysosomal Acidic pH Detection Kit-Green/Red and Green/Deep Red
           Apoptosis detection in multiple samples Annexin V Apoptosis Plate Assay Kit
           Cell proliferation/ cytotoxicity assay Cell Counting Kit-8 and Cytotoxicity LDH Assay Kit-WST
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

 

Multiple staining with oxidative stress-related markers using Doxorubicin-induced senescent cells(flow cytometry)

Using A549 cells induced to senescence by doxorubicin (DOX) and normal cells (CTRL), changes in oxidative stress-related markers in senescent cells were analyzed by flow cytometry with multiple staining. SA-βGal as a senescence marker was detected by Cellular Senescence Detection Kit - SPiDER Blue, total ROS as an oxidative stress marker was detected by ROS Assay Kit - Photo-oxidation Resistant DCFH-DA-, and γH2AX as a DNA damage marker was detected by DNA Damage Detection Kit - γH2AX-Red. As a result, total ROS and γH2AX were increased in SA-βGal-positive senescent cells, and the increase in oxidative stress-related markers associated with cellular senescence could be detected by multiple staining.


  Flow cytometry:SONY SA3800
  SPiDER Blue: PacificBlue  
    ROS Assay Kit: FITC
    γH2AX - Red: Cy3

<Experimental Procedure>
 *Cellular senescence was induced in A549 cells by DOX (0.2 μM DOX for 3 days → normal medium for 3 days)
 The detail procedure for this experiment, please refer to the product page: SPiDER Blue.

 


 

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