Selegiline (low-dose) — The MAO-B Inhibitor
Selegiline is a selective MAO-B inhibitor traditionally used to treat Parkinson's disease by preserving dopamine levels in the brain. In longevity research, low-dose selegiline is of interest for its neuroprotective effects, ability to reduce oxidative stress, and consistent lifespan extension observed in multiple mammalian models.
Mechanism of Action
Selegiline is an irreversible, selective inhibitor of monoamine oxidase B (MAO-B) at low doses. By inhibiting MAO-B, it prevents the breakdown of dopamine in the brain, reducing oxidative stress and the production of reactive oxygen species (ROS) associated with dopamine metabolism. It also exhibits neuroprotective properties independent of MAO-B inhibition, potentially by upregulating antioxidant enzymes like superoxide dismutase (SOD) and catalase, and by preventing apoptosis through the stabilization of mitochondrial membrane potential.
Human Trial Evidence
No published human longevity trials. Animal/in-vitro evidence only. It has been extensively studied in humans for Parkinson's disease and depression, but lifespan extension data is limited to mammalian models like rats and dogs.
Dosing Protocol
1–5 mg/day is the typical low-dose range used for longevity and cognitive enhancement, often taken in the morning to avoid insomnia. Higher doses (10 mg/day) are used for Parkinson's disease but lose MAO-B selectivity. Prescription required in most countries.
Safety & Contraindications
Generally well-tolerated at low doses (<5 mg/day) where it remains selective for MAO-B. At higher doses, it loses selectivity and inhibits MAO-A, requiring dietary tyramine restrictions to prevent hypertensive crisis (the 'cheese effect'). Contraindicated with SSRIs, SNRIs, tricyclic antidepressants, and certain opioids due to the risk of serotonin syndrome.