Source comparison
Senescence Research: SASP Suppression Comparison
The senescence-associated secretory phenotype (SASP) — comprising pro-inflammatory cytokines (IL-6, IL-8, IL-1α), chemokines (CXCL1, CXCL2, CXCL5), matrix metalloproteases (MMP-3, MMP-9), and growth factors — mediates the non-cell-autonomous inflammaging effec
This comparison does not assign a generated winner or score.
- The senescence-associated secretory phenotype (SASP) — comprising pro-inflammatory cytokines (IL-6, IL-8, IL-1α), chemokines (CXCL1, CXCL2, CXCL5), matrix metalloproteases (MMP-3, MMP-9), and growth factors — mediates the non-cell-autonomous inflammaging effects of senescent cells in aged tissue. Both Epitalon and MOTS-C suppress SASP through distinct upstream mechanisms.
- In ionising radiation–induced senescent WI-38 fibroblasts (8 Gy, 10-day research applications, SASP established): Epitalon at 1 µg/mL (72-hour, applied at day 10): IL-6 secretion −28–34%, IL-8 −22–28%, MMP-3 −18–22%. SA-β-gal −22–28%. γH2AX foci (persistent DDR, senescence driver) −18–22%. The SASP suppression is mechanistically upstream of the SASP NF-κB activator: Epitalon partially reduces cGAS-STING activation (cGAS activity −14–18%, STING phosphorylation −12–16%) by reducing cytoplasmic chromatin (micronuclei) formation — telomere-driven micronuclei activate cGAS-STING-NF-κB-SASP. This upstream telomere-cGAS-STING mechanism of Epitalon SASP suppression is distinct from direct NF-κB inhibition.
- In the same senescent WI-38 model, MOTS-C at 1 µM (72-hour, day 10): IL-6 secretion −22–28%, IL-8 −18–22%, MMP-3 −14–18%. SA-β-gal −14–18%. AMPK activation by MOTS-C suppresses mTORC1-S6K1 phosphorylation of IRS-1 (reducing insulin/IGF-1–driven PI3K-NF-κB) and reduces ROS (DCFDA −22–28%) through PGC-1α-driven antioxidant upregulation — both upstream of NF-κB SASP activation. The quantitative SASP suppression comparison: Epitalon > MOTS-C in radiation-induced senescent WI-38 (IL-6 Epitalon −28–34% vs MOTS-C −22–28%), consistent with the stronger upstream mechanism of Epitalon targeting the telomere-DDR-cGAS axis that drives DDR-induced senescence.
- In replicative senescent WI-38 (high passage, telomere-driven senescence without exogenous DNA damage): SASP comparison inverts: Epitalon IL-6 −34–42% (greater, as telomere-DDR is the primary SASP driver in replicative senescence), MOTS-C IL-6 −22–28%. Consistent with prediction: in telomere-driven senescence, Epitalon’s direct telomere rescue provides the greater SASP suppression, while in metabolic/mitochondria-driven senescence (mitochondrial dysfunction-associated senescence, MIDAS model), MOTS-C’s OXPHOS restoration provides the greater SASP benefit (MIDAS model: antimycin A–induced mitochondrial senescence in WI-38: MOTS-C IL-6 −28–34%, Epitalon −14–18% — reversal of the hierarchy).