Lysergic Acid Diethylamide extends lifespan in Caenorhabditis elegans

Abstract

Aging is modulated by nutrient-sensing pathways that integrate metabolic and hormonal cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR), a well-established intervention, extends longevity in diverse species primarily through inhibition of the TOR signaling pathway. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains largely unexplored in the context of aging. Here, we show that LSD treatment significantly extends lifespan in Caenorhabditis elegans and reduces age-associated lipofuscin accumulation, indicative of delayed cellular aging. LSD reproduces several CR-like phenotypes, including decreased reproductive output and increased nuclear localization of the transcription factor PHA-4/FOXA, without affecting food intake. Moreover, LSD treatment reduces lipid stores and downregulates global protein synthesis, both hallmark signatures of TOR inhibition. These findings establish LSD as a modulator of evolutionarily conserved longevity pathways and suggest that psychedelic signaling can mimic a caloric restriction-like metabolic state, paving the way for the development of novel geroprotective strategies.