#1

Fibrosis, characterized by excessive deposition of extracellular matrix (ECM), is a hallmark of biological aging, associated with reduced tissue function and increased morbidity. Effective modulation or slowing of fibrosis holds significant geroprotective potential.

The causal mechanisms of fibrosis are thought to be:

  • Chronic inflammation and immune dysregulation
  • Cellular senescence and senescence-associated secretory phenotype
  • Impaired extracellular matrix remodeling
  • Oxidative stress and mitochondrial dysfunction
  • Reduced regenerative capacity (e.g., stem cell depletion)

From this list, it is easy to see several geroprotectives that may exert multiple effects.

Following are supplements in my regimen for which there is evidence of direct or secondary beneficial effects on organ fibrosis.

  • Curcumin: NF-κB/TGF-β modulation, anti-inflammatory; liver, cardiac, and renal fibrosis reduction.

  • Quercetin: Senolytic, anti-inflammatory, lung and kidney fibrosis reduction (may be similar for Fisetin but less evidence).

  • Astaxanthin: Strong antioxidant, anti-inflammatory; cardiac, liver, and renal renal fibrosis reduction (mostly pre-clinical evidence).

  • NAC: Reduces oxidative stress, glutathione precursor, clinical evidence of reduction in lung fibrosis.

  • Glycine: Collagen synthesis modulation, anti-inflammatory, renal and liver fibrosis reduction (mostly preclinical).

  • Metformin: AMPK activation, anti-inflammatory, anti-senescence; cardiac, liver, and kidney fibrosis reduction.

  • ARBs (telmisartan being the most potent): Blocks Angiotensin II, TGF-β signaling reduction. Most evidence in cardiac and kidney fibrosis reduction.

I’m sharing this and inviting commentary as a preliminary assessment limited to the supplements already in my daily stack for other but not entirely unrelated reasons. Fibrosis, per se, seems to be under addressed as a geroprotective strategy.

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#2

Interesting topic. I was surprised that nattokinase, serrapeptase and lumbrokinase were not in the anti-fibrotic line up. Any idea as to why/why not?

I take a few of the supplements on the list in rotation, so I may already be hedging my bets on this one.

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