Effects of advanced paternal age on trajectories of social behavior in offspring

<jats:p>Our study is the first investigation of the effects of advanced paternal age (<jats:styled-content style="fixed-case">APA</jats:styled-content>) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between <jats:styled-content style="fixed-case">APA</jats:styled-content> and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (<jats:styled-content style="fixed-case">C57BL</jats:styled-content>/<jats:styled-content style="fixed-case">6J</jats:styled-content>) across postnatal development (<jats:italic>N</jats:italic> = 104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a <jats:italic>de novo</jats:italic> origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between <jats:styled-content style="fixed-case">APA</jats:styled-content>, age‐related changes in the paternal sperm <jats:styled-content style="fixed-case">DNA</jats:styled-content> and neurodevelopmental disorders in their offspring.</jats:p>