Chronic LSD administration in rats produced prefrontal cortex gene expression profiles strongly anti-correlated with those characterizing human brain ageing, and to a lesser degree with dementia-associated programmes, an effect reproduced in mice across multiple acute doses and stronger than a broad panel of comparator compounds. In primary cortical cultures, short-term LSD exposure attenuated amyloid-β-induced structural, molecular and transcriptional damage. The work establishes a transcriptional rationale for examining psychedelic-associated pathways in age-related cognitive decline.
Key Points
- LSD transcriptional profiles oppose human prefrontal cortex ageing signatures
- Effect reproduced across species, doses, and independent datasets
- LSD reduced amyloid-β-induced damage in primary cortical cultures
Longevity Analysis
Brain ageing is driven in large part by progressive synaptic dysfunction and disrupted neuron–glia communication, meaning interventions that restore cortical signaling architecture matter more than those targeting single pathological proteins. Signature reversion offers a method for identifying such interventions computationally, reading the molecular language of a declining tissue and searching for compounds that speak the opposite. The practical implication is not self-administration but a defined set of neuroplasticity and glial regeneration pathways worth interrogating as cognitive resilience targets.
Original published by Wiley Aging Cell, by Aurora Savino, Carla Liaci, Ilaria Bertani, Simona Rando, Mattia Camera, Giorgio R. Merlo, Lidia Avalle, Valeria Poli, Nereo Kalebic, Francesco Iorio .