[1][2] SASP may also consist of exosomes and ectosomes containing enzymes, microRNA, DNA fragments, chemokines, and other bioactive factors.
[3][4] Soluble urokinase plasminogen activator surface receptor is part of SASP, and has been used to identify senescent cells for senolytic therapy.
[23] Aberrant oncogenes, DNA damage, and oxidative stress induce mitogen-activated protein kinases, which are the upstream regulators of NF-κB.
[24][25] Demethylation of DNA packaging protein Histone H3 (H3K27me3) can lead to up-regulation of genes controlling SASP.
[22][26] Interleukin 1 alpha (IL1A) is found on the surface of senescent cells, where it contributes to the production of SASP factors due to a positive feedback loop with NF-κB.
[27] mTOR inhibition of ZFP36L1 prevents this protein from degrading transcripts of numerous components of SASP factors.
[37] Senescent cells release mitochondrial double-stranded RNA (mt-dsRNA) into the cytosol driving the SASP via RIGI/MDA5/MAVS/MFN1.
[42] SASP disrupts normal tissue function by producing chronic inflammation, induction of fibrosis and inhibition of stem cells.
[43] Transforming growth factor beta family members secreted by senescent cells impede differentiation of adipocytes, leading to insulin resistance.
[44] SASP factors IL-6 and TNFα enhance T-cell apoptosis, thereby impairing the capacity of the adaptive immune system.
[53][1] In fact, SASP from senescent cells is associated with many aging-associated diseases, including not only cancer, but atherosclerosis and osteoarthritis.
[66] The ability of SASP to clear senescent cells and regenerate damaged tissue declines with age.
[68][69] Senescent cells have permanently active mTORC1 irrespective of nutrients or growth factors, resulting in the continuous secretion of SASP.
[71] The protein hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) antagonizes cellular senescence and induction of the SASP by stabilizing Oct-4 and sirtuin 1 mRNAs.
[11] Chronic inflammation due to SASP can suppress immune system function,[3] which is one reason elderly persons are more vulnerable to COVID-19.