Manipulation of serotonin signal suppresses early phase of behavioral aging in Caenorhabditis elegans

Aging is associated with progressive changes in behavioral functions, in part caused by muscle frailty, called sarcopenia. However, it was not clear whether certain neurotransmitters are directly involved in behavioral aging. Here we investigated aging of locomotion behaviors with an associative learning property, called basal and enhanced slowing response in Caenorhabditis elegans. Basal slowing response is a modest slowdown in response to food, while enhanced slowing response is a greater slowdown response when animals experience starvation. The behaviors are mediated by dopamine and serotonin, respectively. During aging, basal slowing response was increased, resulting in a diminished difference between the two slowing responses. The behavioral change occurred during early phase of aging prior to the timing when sarcopenia was observed in previous studies. Interestingly, expression of a serotonin biosynthesis marker, tph-1∷GFP, was increased in old animals. Serotonin receptor antagonists and deletion mutants of their target receptor genes (ser-1 and ser-4) partially suppressed age-related changes in locomotion behaviors. Thus, manipulating serotonin signal at receptor levels suppresses early phase of locomotion aging.