Natural and Pathological Aging Distinctively Impacts the Pheromone Detection System and Social Behavior

Normal aging and many age-related disorders such as Alzheimer’s disease cause deficits in olfaction; however, it is currently unknown how natural and pathological aging impacts the detection of social odors which might contribute to the impoverishment of social behavior at old age further worsening overall health. Analysis of the vomeronasal organ, the main gateway to pheromone-encoded information, indicated that natural and pathological aging distinctively affects the neurogenic ability of the vomeronasal sensory epithelium. Whereas cell proliferation remained majorly preserved in 1-year-old APP/PS1 mice, naturally aged animals exhibited significant deficiencies in the number of mature, proliferative, and progenitor cells. These alterations may support age-related deficits in the recognition of social cues and the display of social behavior. Our findings indicate that aging disrupts the processing of social olfactory cues decreasing social odor exploration, discrimination, and habituation in both wild-type senescent (2-year-old) mice and in 1-year-old double mutant model of Alzheimer’s disease (APP/PS1). Furthermore, social novelty was diminished in 1-year-old APP/PS1 mice, indicating that alterations in the processing of social cues are accelerated during pathological aging. This study reveals fundamental differences in the cellular processes by which natural and pathological aging disrupts the exploration of social information and social behavior. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12035-023-03362-3.