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Cellular Senescence is a state of cells where they stop taking an active dividing role in the tissue but at the same time refuse to react to the natural signals to “commit cell suicide”. This leaves them in a state where they are useless and inactive but more so secrete substances (cytokines and extracellular vesicles) with clearly negative effects. This secretion became infamous under the “Senescence Associated Secretory Phenotype (SASPs)”. More than just a negative stimuli for all surrounding cells and the immune system, the state of Senescence and SASPs are now regarded as one of the pillars of aging itself, possibly even the single most important one. Enough senescent cells will kill you but the usual mechanism is that they induce age-related fatal diseases which then end life (assuming no other cause of death ends life before that obviously).

Osteoarthritis effects large parts of the population being one of the main causes of pain and disability in an aging population. Classified as a chronic inflammatory disease, the mystery in OA was where the inflammatory molecules were coming from. New work published in Nature Medicine brings at least in part an answer to this question. The main driving factors for OA appear to be Senescent Cells and their SASPs. Clearance of these cells with a compound that is already medically approved (though for a different application with different dosing) they could show significant and life long lasting improvement in a mouse model even after a single injection.

There are other new drug candidates to induce senescent cell clearing. They range from nutrition supplements (Quercitin), available chemotherapeutic agents (Dasatnib, Navitoclax) (due to a related suicide suppression mechanism of cancer cells with senescent cells) over experimental small molecules (ABT263). But also gene therapeutic approaches and designed specific peptides are among the candidates for started race for the best (most specific and least toxic) senescent cell clearing substance.

In another Nature Paper, the regenerative factors for the Stem Cell Secretome, namely extracellular vesicles, is described. In combination, Senescent Cell Clearing followed by the proliferation inducing paracrine effects of the Stem Cell Secretome are likely to fundamentally change the way medicine think about and Treat OA.

 

Links:

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment

https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4324.html

 

Extracellular vesicles — new tool for joint repair and regeneration

http://www.nature.com/nrrheum/journal/v12/n4/full/nrrheum.2015.170.html

 

 

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