Urolithin A, Spermidine and Fisetin: Comparing the Longevity Compounds

With the supplement aisle now full of longevity compounds marketed almost interchangeably, this review does the useful work of comparing four of the best-studied by mechanism rather than by marketing claim: spermidine, fisetin, berberine and urolithin A. The authors' central point is that these compounds are not competing for the same job. Spermidine induces broad autophagy, the cell's general clean-up process; fisetin selectively clears senescent 'zombie' cells; berberine acts on metabolic regulation and gut bacteria, with the largest existing clinical dataset of the four; and urolithin A is the most targeted of the group, acting specifically on mitophagy, the clean-up of damaged mitochondria. As a narrative review, it doesn't run new trials of its own, and clinical evidence quality still varies considerably between the four compounds, strongest for berberine, thinnest for fisetin. A brief honest note: this review examines four complementary longevity compounds rather than the narrower urolithin A/NAD+/spermidine comparison sometimes cited elsewhere, but it covers the same underlying question thoroughly and transparently.