Chloroquine — The Lysosomal Inhibitor
Chloroquine is a well-known antimalarial and immunosuppressive drug that functions as a lysosomal inhibitor. In the context of longevity and aging research, it is primarily utilized as an experimental tool to block late-stage autophagy, enabling the measurement of autophagic flux.
Mechanism of Action
Chloroquine diffuses into lysosomes where it becomes protonated, effectively neutralizing the acidic pH of the lysosomal lumen. This alkalinization impairs the function of resident acid hydrolases and prevents the fusion of autophagosomes with lysosomes. As a result, late-stage autophagy is inhibited, leading to the accumulation of autophagosomes. While enhancing autophagy is generally considered a pro-longevity strategy, chloroquine's targeted inhibition makes it a critical pharmacological control for assessing autophagic capacity and cellular clearance mechanisms.
Human Trial Evidence
No published human longevity trials. Animal/in-vitro evidence only. While chloroquine is widely used in humans for malaria and autoimmune diseases, its autophagy-inhibiting properties make it counterproductive as a clinical longevity intervention.
Dosing Protocol
Not recommended for longevity or anti-aging purposes. For its FDA-approved indications, such as malaria prophylaxis or rheumatoid arthritis, dosing typically ranges from 250 to 500 mg (weekly or daily depending on the condition), strictly under medical prescription.
Safety & Contraindications
Prescription only. Chronic administration carries a significant risk of irreversible retinopathy and macular degeneration. Other serious adverse effects include QT interval prolongation, cardiomyopathy, and neuromyopathy. It is contraindicated in individuals with pre-existing retinal changes or porphyria.