Learning path8 compounds · ~22 min

Senolytics + longevity foundations

Fisetin, quercetin, spermidine, NMN, urolithin A. mTOR modulators next (rapamycin, metformin). The Attia-Sinclair reading list.

  1. 01Fisetin
    t½ ~2 hours

    Flavonoid polyphenol found in strawberries, apples, and persimmons. Functions as a senolytic by inhibiting the PI3K/AKT/mTOR survival pathway and BCL-2/BCL-XL anti-apoptotic protei…

  2. 02Quercetin
    t½ ~11 hours

    Ubiquitous dietary flavonoid functioning as a senolytic adjunct, anti-inflammatory, and antioxidant. Inhibits BCL-2 family anti-apoptotic proteins in senescent cells, working syner…

  3. 03Spermidine
    t½ Variable (rapidly metabolized and incorporated into polyamine pools)

    Natural polyamine that induces autophagy through inhibition of the acetyltransferase EP300 (p300), leading to deacetylation of core autophagy proteins including ATG5, ATG7, ATG12, …

  4. 04NMN (Nicotinamide Mononucleotide)
    t½ ~3 hours

    Direct precursor to nicotinamide adenine dinucleotide (NAD+) via the salvage pathway enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). Bypasses the rate-limiting NAMP…

  5. 05urolithin-a — entry pending
  6. 06Resveratrol
    t½ 1-3 hours (parent compound), 9.2 hours (metabolites)

    Polyphenolic stilbene that activates SIRT1 deacetylase through an allosteric mechanism, enhancing deacetylation of PGC-1alpha and FOXO transcription factors. Improves mitochondrial…

  7. 07Rapamycin (Sirolimus)
    t½ 62 hours

    Selective inhibitor of mTORC1 at low doses, suppressing the nutrient-sensing pathway that drives cellular growth and proliferation. Periodic inhibition upregulates autophagy, reduc…

  8. 08Metformin
    t½ 6.2 hours

    Activates AMPK via inhibition of mitochondrial complex I, reducing hepatic glucose output and improving peripheral insulin sensitivity. Secondary effects include suppression of mTO…

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