Slowing Fibrosis as Geroprotective Strategy

#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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#3

There are many older, and newer, drugs that seem to have anti-fibrotic effects…

and supplements as you’ve suggested, though I suspect the impact of the drugs is probably much greater…

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#4

One good start is to consider the different Root Causes of Fibrosis in Human Organs. And then see what we can learn about the different triggers and mechanisms that are in action.

Ex. Heart: Where pressure overload → fibroblast proliferation → stiffened myocardium.

As I see it slowing fibrosis is fruitful Since fibrosis is the excessive deposition of extracellular matrix (ECM) components, primarily collagen, leading to scarring and loss of organ function. The exact mechanisms vary by organ, the root causes generally involve chronic inflammation, repetitive injury, and dysregulated tissue repair. (like @RobTuck said above). I agree with the supplements that arementioned.

That being said, it is hard to find effective general interventions that targets the general slowdown of agerelated fibrosis.

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#5

There are also a number of pharmaceuticals designed to treat pulmonary fibrosis, including the newer nerandomilast which reduces fibrosis primarily by modulating inflammation and fibroblast activity but my discussion was limited to supplements I am taking for other purposes. I agree that it is reasonable to examine supplements like nattokinase to see if the enzyme could survive and persist in action at a level necessary to reduce the rate of organ fibrosis. So far, I have not seen such evidence. My take is that the difference between dissolving fibrin in a blood clot or atherosclerotic plaque, on the one hand, and remodeling dense, collagen-rich fibrotic tissue in an organ, on the other, is substantial.

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#6

I take ezetimibe and therefore it should have been on my list as a mostly pathology-targeted approach. Its effects on fibrosis are most well supported in the liver where it counters the fibrosis driven by the specific metabolic derangement of lipotoxicity. Its value is well-supported for conditions like NASH. Much of the data is based on clinical observations though.

I’m not taking spermidine at the moment but it represents a hallmark-of-aging-targeted approach to fibrosis. Reviewing the research makes me think I should resume taking it since it is restorative to a fundamental cellular process critical for health across all organs, giving it broader support in combating age-related fibrosis. One LLM summary noted: Strong preclinical evidence supports significant antifibrotic potential across multiple organs through autophagy and senescence modulation. Early clinical data demonstrate beneficial effects on human cardiovascular health and improved markers of aging, though specific antifibrotic human trials are ongoing or limited. Considered promising for broad geroprotection, particularly for age-related cardiovascular and hepatic fibrosis. Before stopping, I had been taking 10 mg/day spermidine. Looking more closely at the research, I think 5 mg or less is prudent.

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#7

I’ve been taking the Blueprint essentials capsule, and while it’s not inexpensive at $46, I keep choosing this option because it contains 10mg of spermidine.

My thought is once you buy spermidine separately, that daily multi seems, to me, to be a bargain. I’m always stumped why I’m the only one taking it :slight_smile:

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#8

I don’t understand the desire to produce more collagen if this is the root cause of excess fibrosis. I’ve tried to amend discussion on elastin to counteract the excess collagen deposition, and the interplay of LoxL for cross linking in the ECM. So glycine, proline, and vitamin c supplementation to increase collagen but if this isn’t balanced with elastin production, I’d be worried about fibrosis.