Year: 2025
Type: article
Abstract: Many elements of an organism’s behavior are intertwined with the organism’s health. Over a long period of time, health status is also indicative of life span, with improved health correlating with a longer life. However, the relationship between longevity and behavior remains relatively unexplored. Here, we report that modification of a single longevity gene downstream of dietary restriction and hypoxia markedly alters behavior in Caenorhabditis elegans . We found that modified expression of flavin-containing monooxygenase ( fmo-2 ) leads to altered sensory perception and decision-making in a variety of behavioral paradigms. This cell nonautonomous signaling pathway is linked to changes in tryptophan metabolism, where loss of fmo-2 requires the tryptophan metabolite serotonin and overexpressed fmo-2 requires the tryptophan metabolite quinolinic acid to change behavior. These results suggest a unique mechanism for gut metabolism to communicate positive satiety signals and negative depressive signals to the organism by modifying an essential amino acid. They also demonstrate the importance of examining pleiotropic effects in promising longevity interventions.
Source: Science Advances
Institution: University of Michigan
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Mechanistic understanding of host-microbe interactions in regulating stress response and lifespan, G3223614423, Mechanisms of the cell non-autonomous dietary restriction pathway, Determining the neural mechanisms of mechanosensory food perception in DR-mediated longevity, Flavin-containing monooxygenases in endogenous metabolism and aging, Claude D. Pepper Older Americans Independence Center at the University of Michigan (UM Pepper Center)
OpenAlex ID: W4415525428