Natural and pathological aging distinctively impacts the vomeronasal system and social behavior

Abstract

The sense of smell, known as olfaction, is greatly affected by age, with older individuals often experiencing a decline in their ability to smell. These deficits are typically permanent and can significantly impact their quality of life, eating habits, and may serve as early indicators of cognitive decline, and dementia. Despite their impact in life quality, we currently lack basic understanding regarding the effects of both natural and pathological aging on the ability to smell. A particularly intriguing category of olfactory information pertains to social odors, the disruption of which could potentially contribute to reduced social interactions and increased health issues.

Our study of the vomeronasal organ, which serves as the primary gateway for pheromone-encoded information, revealed distinct effects of both natural and pathological aging on the neurogenic capacity of the vomeronasal sensory epithelium. In an animal model of Alzheimers disease (double mutant APP/PS1 mice), cell proliferation largely remained intact, but naturally aged animals showed significant deficiencies in the number of mature, proliferative, and progenitor cells.

Our findings suggest that aging hinders the processing of social olfactory cues, leading to reduced exploration, discrimination, and habituation to social odors in both wild-type senescent mice (2-year-old) and in 1-year-old APP/PS1 mice. These changes may contribute to age-related difficulties in recognizing social cues and displaying social behaviors. As expected, social novelty was diminished in 1-year-old APP/PS1 mice, indicating that alterations in the processing of social cues occur more rapidly in pathological aging. This study unveils fundamental differences in the cellular processes through which natural and pathological aging disrupt the exploration of social information and social behavior.