Why are they so much less prevalent among longevity-inducing/hormetic compounds than plant-based alkaloids/phytochemicals?
they are MUCH less well-known, so there’s also some opportunity for “unknown unknowns”
====
Marine Alkaloids & Longevity Pathways — Cheat Sheet
| Alkaloid | Source organism | Primary target / pathway | Aging-relevant mechanism | Evidence level |
|---|---|---|---|---|
| Psammaplysene A | Sponge (Psammaplysilla) | Prevents FOXO nuclear export | Maintains FOXO3a in nucleus → stress resistance, longevity axis |
 Cell/animal neuroprotection; no lifespan |
| Meridianins (A–H) | Tunicates (Aplidium, Synoicum) | GSK-3β & CDK inhibitors | Lithium-like effect → NRF2 stabilization, insulin/IGF signaling modulation |
Rodent brain models; no lifespan |
| Manzamine A | Sponges (Haliclona, Acanthostrongylophora) | GSK-3β / CDK5 inhibition | Autophagy modulation, kinase stress responses |
Preclinical (cancer, malaria); aging link speculative |
| Hymenialdisine | Sponges (Axinella, Acanthella) | CDK/GSK-3 inhibition | Same lithium-like pathway; anti-inflammatory |
Cell/animal models, not tested for longevity |
| Aaptamine | Sponge (Aaptos) | Nrf2 / MAO-A modulation | Induces HO-1, NQO1 → antioxidant response |
UV/oxidative stress cell models; no lifespan |
| Anabaseine / DMXB-A (GTS-21) | Nemertean worm alkaloid (synthetic analogs) | α7 nAChR agonist | Cholinergic anti-inflammatory reflex; neuroprotection |
Animal models + human cognitive trials; no lifespan |
| Caulerpin | Green alga (Caulerpa) | PPARα/γ agonist | Metabolic health, NF-κB suppression, anti-inflammatory |
Worm extracts, rodent models; no direct lifespan |
| Crambescin C1 | Sponge (Crambe crambe) | NO & metallothionein induction | Stress response (metal detox, vasodilation) |
Cell + rat vascular models; no lifespan |
What this means
- Most marine alkaloids are cytotoxic WMDs (e.g. ecteinascidins, dolastatins) → not longevity candidates.
- A handful hit hormetic nodes (FOXO, GSK-3/NRF2, AMPK/PPAR, cholinergic signaling).
- Evidence gap: except for lithium (terrestrial ion), no marine alkaloid has been shown to extend lifespan in worms/flies/mice. Right now, they’re mechanistically intriguing, not proven geroprotectors.
Next step could be: I can sketch a “target map” diagram — showing how these compounds sit on the classic longevity pathways (FOXO ↔ GSK-3 ↔ NRF2 ↔ AMPK/PPAR ↔ cholinergic anti-inflam) so you can see overlaps and missing pieces. Want me to?