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Lysergic Acid Diethylamide extends lifespan in Caenorhabditis elegans

Carrilho, B. d. S.; Silva, A. D.; Sant Anna, A. M. K.; Ventura, M. A. V. d. C.; Moll, F. T.; Aguilaniu, H.; Domith, I.; Rehen, S. K.

2025-06-17 neuroscience
10.1101/2025.06.16.659936 bioRxiv
Show 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.

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