ABSTRACT: Previous functional imaging studies have identified the role of central autonomic network (CAN) in autonomic regulation during various tasks. However, its variability with respect to gender and age, particularly in the resting state, remains poorly understood. Therefore, in this study we systematically investigated gender- and age-related differences in the resting-state functional connectivity (rsFC) seeded from core regions of this network, namely posterior mid-cingulate gyrus (pMCC), left amygdala, right anterior and left posterior insula, and ventromedial prefrontal cortex (vmPFC), using a large cross-sectional adulthood sample. Results revealed that each of the seeded connectivity maps engaged in at least one of the large-scale brain networks including sensorimotor, attentional, basal ganglia, limbic, and default mode networks (DMN). In the early-adulthood stage, females had stronger negative rsFC in pMCC and right anterior INS (aINS) with the medial DMN than males, possibly reflecting their greater suppression of the sympathoexcitation associated with sex hormonal estrogen. Whereas in the late-adulthood stage, they showed stronger positive rsFC in pMCC with postcentral gyrus and weaker negative rsFC with the most DMN, possibly relating to their higher risk of depression, anxiety, and dementia than males after menopause. Moreover, females demonstrated reduced negative rsFC in pMCC with dorsal PCUN/PCC and left AG with advancing age, whereas males showed the opposite pattern, namely increased positive rsFC, in pMCC with right SMG, and in vmPFC with ventral PCUN. We interpret these results as their differences of altered autonomic regulation associated with pain experience and reflective movement, respectively, due to aging. In sum, our findings add in literature that autonomic responses can be also represented intrinsically in the resting brain, and gender- and age-related differences might be associated with sex hormones and sensorimotor abilities, respectively.