Lysergic acid diethylamide extends lifespan in Caenorhabditis elegans.
8 affiliations
- 1Institute of Biomedical Sciences, Graduate Program in Morphological Sciences, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21941-902, Brazil.
- 2D'Or Institute for Research and Education (IDOR), Rio de Janeiro, 22281-100, Brazil.
- 3IDOR Pioneer Science Initiative, Rio de Janeiro, 22281-100, Brazil.
- 4Serrapilheira Institute, Rio de Janeiro, Rio de Janeiro, 22431-050, Brazil.
- 5D'Or Institute for Research and Education (IDOR), Rio de Janeiro, 22281-100, Brazil. [email protected].
- 6IDOR Pioneer Science Initiative, Rio de Janeiro, 22281-100, Brazil. [email protected].
- 7D'Or Institute for Research and Education (IDOR), Rio de Janeiro, 22281-100, Brazil. [email protected].
- 8Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. [email protected].
Abstract
Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in Caenorhabditis elegans by up to 17.6% at the 25% survival timepoint, and reduces age-associated lipofuscin accumulation. This response involves serotonergic GPCR signaling: LSD failed to extend lifespan in ser-1 and ser-5 mutants and shortened lifespan in ser-4 and ser-7 mutants, yet remained effective, although with reduced magnitude, in tph-1 animals deficient in serotonin synthesis, indicating that endogenous serotonin production is not strictly required. LSD also elicited phenotypes that overlap with CR, including reduced reproductive output, smaller body size, delayed vulval development, and time-dependent remodeling of lipid stores and PHA-4 levels, while adult food-consumption assays detected no reduction in feeding under the conditions tested. Notably, the lifespan benefit was absent in eat-2 mutants and was lost under bacterial dilution, where LSD instead shortened lifespan, indicating that nutritional context shapes the response. Transient exposure during early adulthood was sufficient to extend lifespan. Together, these findings identify LSD as a tool to investigate how serotonergic signaling interfaces with conserved longevity-related pathways.
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BibTeX
@article{carrilho2026lysergic,
title = {{Lysergic acid diethylamide extends lifespan in Caenorhabditis elegans.}},
author = {Beatriz S Carrilho and Aline Teixeira Duarte Silva and Isabelle Martins and Ariane Moura and Manuela Vilas and Matheus Antonio V C Ventura and Francisco Moll and Hugo Aguilaniu and Ivan Domith and Stevens Rehen},
journal = {Biogerontology},
year = {2026},
month = oct,
doi = {10.1007/s10522-026-10521-1},
url = {https://europepmc.org/article/MED/42911464},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lysergic acid diethylamide extends lifespan in Caenorhabditis elegans.
AU - Beatriz S Carrilho
AU - Aline Teixeira Duarte Silva
AU - Isabelle Martins
AU - Ariane Moura
AU - Manuela Vilas
AU - Matheus Antonio V C Ventura
AU - Francisco Moll
AU - Hugo Aguilaniu
AU - Ivan Domith
AU - Stevens Rehen
PY - 2026
DA - 2026/10/22
JO - Biogerontology
DO - 10.1007/s10522-026-10521-1
UR - https://europepmc.org/article/MED/42911464
AB - Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in Caenorhabditis elegans by up to 17.6% at the 25% survival timepoint, and reduces age-associated lipofuscin accumulation. This response involves serotonergic GPCR signaling: LSD failed to extend lifespan in ser-1 and ser-5 mutants and shortened lifespan in ser-4 and ser-7 mutants, yet remained effective, although with reduced magnitude, in tph-1 animals deficient in serotonin synthesis, indicating that endogenous serotonin production is not strictly required. LSD also elicited phenotypes that overlap with CR, including reduced reproductive output, smaller body size, delayed vulval development, and time-dependent remodeling of lipid stores and PHA-4 levels, while adult food-consumption assays detected no reduction in feeding under the conditions tested. Notably, the lifespan benefit was absent in eat-2 mutants and was lost under bacterial dilution, where LSD instead shortened lifespan, indicating that nutritional context shapes the response. Transient exposure during early adulthood was sufficient to extend lifespan. Together, these findings identify LSD as a tool to investigate how serotonergic signaling interfaces with conserved longevity-related pathways.
SN - 1389-5729
SN - 1573-6768
ER -