Moll, F. T. | bioRxiv Science

bioRxiv2025

Lysergic Acid Diethylamide extends lifespan in Caenorhabditis elegans

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 through modulation of conserved nutrient-sensing pathways, including TOR signaling. 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, suggesting delayed age-associated decline. LSD induces several phenotypes that overlap with those observed in some caloric restriction paradigms, including reduced reproductive output, decreased body size, and the absence of an additive effect in lifespan assay performed in dietary restriction model, without apparent decreasing in food intake. In addition, LSD treatment modulates lipid stores and other cellular readouts associated with nutrient-sensing physiology. Together, these findings suggest that LSD engages evolutionarily conserved pathways linked to longevity and identify this compound as a tool to investigate serotonergic control of aging biology.

neuroscience↗

bioRxiv2023

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations. Significance statementBrain connectivity is a central topic in neuroscience. Understanding how brain areas can communicate allows for the comprehension of brain structure and function. We have described in rodents a new commissure pathway that connects the cortex to the contralateral thalamus. Here, we investigate whether this pathway exists in non-human primates and humans. The presence of these commissures poses the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

neuroscience↗