Bicep
#2
The study showed that existing drugs targeting the JAK pathway, already approved to treat certain autoimmune diseases, can prevent HMGB1-induced aging in cells.
Anybody know what drugs they’re talking about. Does Rapa do this?
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Well, that certainly opens a FOMO can of worms. 
It appears that HMGB-1 is like mTORC1 in that it is necessary, but we might want to put the brakes on a little bit.
We might start with something relatively benign like: “Glycyrrhizin (licorice-root triterpenoid) – canonical small-molecule binder; reduces HMGB-1-induced cytokines in many rodent models and is already used IV in Asia for hepatitis.”
Maybe we could self-test using CRP to monitor the results?
“Most clinicians reach first for a C-reactive protein (CRP) blood test when they need a quick, inexpensive screen for systemic inflammation. It has largely replaced the older erythrocyte-sedimentation rate (ESR) because CRP rises and falls faster, is more sensitive, and is less affected by age and sex.”
Researchers have designed specific peptides (e.g., a nonapeptide called HBP08) and antibodies that bind to HMGB1 with high affinity, neutralizing it before it can activate receptors.
Status: These are primarily investigational compounds in preclinical research and have not been approved for clinical use. A 2025 study in mice showed that blocking HMGB1 with antibodies could reduce senescent cells and improve muscle regeneration, highlighting its potential in anti-aging.
"HBP08 is a peptide inhibitor of the protein-protein interaction between chemokine (C-X-C motif) ligand 12 (CXCL12) and high mobility group protein B1 (HMGB1).
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It is available, but I am not ready to stick myself with it just yet.
Oddly, maybe we are already modifying it. “Clinically available today: glycyrrhizin (oral or IV); statins; metformin. All have human data showing lowered circulating HMGB-1 in inflammatory conditions.”
Unlocking HMGB1's Role in Aging.
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Lost
#4
Careful. Glycirrhizin mimics mineralcorticoids. Toxicity along these lines is pretty common.
You’re right. "Glycyrrhizin, the active compound in licorice root, can have serious side effects, particularly when consumed in large amounts or over a long period. "
I am not planning to take any of this.
Hey Phred,
Yes rapamycin does this… can be seen in reduction of inflammation from rapamycin use, looking at glycans.
Tamping down senescent cells, prevents spread of this action.
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