The stress system is a key modulator of homeostasis and allows organisms to adapt to environmental changes. Proper survival is dependent on the appropriate stress response, for example initiating food (energy) intake or provoking physical reaction. However, long-term activity of the stress system is related to cardiovascular diseases, metabolic syndromes as well as accelerated aging and cognitive impairments. In order to assess the impacts of stress regulation on cardiac, metabolic and aging health processes, we used lines of rats selected for their differential glucocorticoid responsiveness to stress during juvenile period, in the different experiments presented here. The three lines of rats showed low, intermediate or high response to stress and elicited differences in biobehavioral phenotypes. Cardiovascular diseases are highly exacerbated by stress exposure and autonomic imbalance. Reduced vagal modulation has been related to a lower stress flexibility and deleterious effects on cardiac health. In a first study, we investigated the autonomic nervous system modulation of heart rate in the three lines of rats (differing in their responsiveness to stress). Electrocardiographic recordings were performed at rest and following autonomic pharmacological manipulations. Rats with intermediate reactivity to stress had a higher resting parasympathetic (vagal) modulation and a reduced heart rate compared to rats with low or high stress responses. Furthermore, pharmacological treatments showed that the sympathetic regulation of the heart was not impaired in rats with low and high responsiveness to stress. Stress can affect social interactions and, in return, social interactions can be the cause of critical stress. Furthermore, since the stress system is related to key metabolic mediators, we investigated in a second study, the general metabolism of rats from the three lines. Moreover, we paired rats from the different lines together, in mixed-line dyads, and we evaluated the differences in social interactions and the long-term effects of mixed-line pairing on metabolism. We used indirect calorimetry and mitochondrial respirometry to measure energy expenditure and mitochondrial function. We observed that the selection for differences in glucocorticoid responsiveness induced constitutive differences in energy expenditure and fuel use. Moreover, we showed that the biobehavioral phenotypes affected the social interactions between the different lines. Finally, long-term mixed-line pairing affected global and central metabolism of the rats, with rats from the low and intermediate responsive lines being more susceptible to changes. In a final experiment, we studied the interaction of two risk factors for cognitive decline, the secretion of corticosterone and aging. Indeed, dysfunctions of the stress system contribute and facilitate aging and increased glucocorticoids induce cognitive alterations. We assessed anxiety, stress responsiveness, coping-style and cognitive functions in a Morris water-maze at early-aging. Results indicated that the phenotype of the lines were stable throughout life and that learning, swimming strategies and reversal ability were different between the lines. Overall, we showed that this model is suitable to study the systems related to stress regulation. Future research may use this animal model in order to investigate further the relationship between opposite stress regulation and health.