The Culprit of Aging - Helen Blau's work at Stanford / PGE2, 15-PDGH

#61

Helen blau 's recent presentation on her work Longevity Summit 2025 Reporting

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#62

On the trail of natural inhibitors of 15-pgdh I ended up ordering some dried leaves that are normally put into fish tanks. Im currently wondering how to consume them…

#63

Wondering where the big money biohackers are relative to this topic. Certainly not liking the wait to 2033 for anything available for us bottom feeders.

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#64

What plant?

#65

See this other paper: Licorice Extract Mimics Fasting to Reverse Brain Aging in Mice

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#66

Jackfruit leaves

#67

Brilliant! So putting aside the sodium/ toxicity etc risks we have the increased cancer risks of suppressing 15-pgdh but then again if OA is inhibiting you exercising thats also increasing your cancer risk presumably…

#68

Based on the scientific literature, there is direct preclinical evidence identifying Artocarpus heterophyllus (Jackfruit) extracts as potent inhibitors of 15-hydroxyprostaglandin dehydrogenase (15-PGDH).

While there are no Phase I-III clinical trials specifically testing Jackfruit leaves for 15-PGDH inhibition in humans to date, in vitro and animal data strongly support this mechanism.

1. The Core Scientific Evidence

The “smoking gun” evidence comes from a screening study that identified Artocarpus heterophyllus as a top candidate among 98 medicinal plants for this specific enzymatic activity.

  • Study: In-vitro Wound Healing Effect of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor from Plant (PubMed ID: 28479736).
  • Findings: The ethanol extract of Artocarpus heterophyllus (EEAH) was identified as a potent 15-PGDH inhibitor.
  • Potency: It demonstrated an IC50 of 0.62 µg/mL, which is considered highly potent for a crude natural extract.
  • Mechanism Observed: The extract inhibited 15-PGDH activity, leading to a concentration-dependent elevation of Prostaglandin E2 (PGE2) levels in HaCaT (keratinocyte) cells.
  • Result: This elevation in PGE2 accelerated wound closure in scratch assays, validating the regenerative mechanism.

2. Mechanism of Action: The “Gerozyme” Connection

For a longevity specialist, the context of this inhibition is critical. 15-PGDH is currently characterized as a “gerozyme” (an aging-associated enzyme) by researchers like Helen Blau at Stanford.

  • The Pathway: 15-PGDH degrades PGE2.
  • The Logic: PGE2 is essential for tissue regeneration (muscle stem cell proliferation, mitochondrial function, cartilage repair). As mammals age, 15-PGDH levels rise, PGE2 levels fall, and regenerative capacity declines.
  • Jackfruit’s Role: By inhibiting 15-PGDH, the active compounds in Jackfruit leaves/bark “spare” PGE2, effectively mimicking the regenerative environment of younger tissue. This is the same mechanism of action as the synthetic drug SW033291, which has been shown to regenerate muscle mass and liver tissue in aged mice.

3. Source Material & Extraction

The evidence points specifically to ethanolic extracts, not aqueous (water) teas.

  • Leaves vs. Bark: While the primary 15-PGDH study utilized a general extract (likely aerial parts), related studies confirm that Jackfruit leaves specifically contain the bioactive prenylated flavonoids (such as artocarpin, artocarpesin, and norartocarpetin) responsible for this activity.
  • Solubility: These bioactive flavonoids are poorly soluble in water. Scientific data suggests that to achieve the 15-PGDH inhibitory effect, an alcohol-based extraction (ethanol) is required to pull the necessary prenylflavonoids from the leaf matrix.

4. Clinical Evidence & Gaps

  • Clinical Evidence: None. There are no registered clinical trials validating Jackfruit leaf extract specifically for 15-PGDH inhibition in humans. Current human evidence is limited to traditional use for wound healing and diabetes (which involves different pathways).
  • Animal Evidence: Strong. Studies on diabetic rats and wound models show that Jackfruit leaf extracts accelerate tissue repair, a phenotype consistent with elevated PGE2 levels via 15-PGDH inhibition.

Summary of Data

Parameter Evidence Status Notes
Target Confirmed Inhibits 15-PGDH enzyme in vitro.
Potency High IC50 = 0.62 µg/mL (Ethanol extract).
Bioactives Identified Likely prenylated flavonoids (Artocarpin, Artocarpesin).
Human Data Missing No clinical trials confirm this specific pathway in humans yet.
Extraction Critical Must be Ethanolic; water extracts likely inactive for this target.

Conclusion

The scientific evidence validates that ethanol extracts of Jackfruit leaves/biomass are potent 15-PGDH inhibitors in vitro, capable of elevating PGE2 and driving regeneration. This offers a natural analogue to synthetic 15-PGDH inhibitors currently under investigation for sarcopenia and tissue rejuvenation.

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#69

I havent been able to find any source of extract here in the UK so ended with a bunch of fishtank leaves from India on ebay. I can find fruit extract but not leaf extract and presumably I would need the latter. Does the above mean that if I blend the leaves up with water and drink them its not going to have the same impact as extracting the active elements using ethanol? Or is ethanol extraction just a way of avoiding eating a lot of leaves? I guess this is a little academic as ive now ordered some liquorice root extract…

#70

How do you to measure effectiveness?