Objectives Aging is associated with changes in resting energy expenditure (REE) and body composition. We investigated the association between age and changes in REE in men and women stratified by body mass index (BMI) categories (normal weight, overweight and obesity). We also examined whether the age-related decline in REE was explained by concomitant changes in body composition and lifestyle factors. Study design Cross-sectional. Main outcome measures 3442 adult participants (age range: 18-81 y; men/women: 977/2465) were included. The BMI range was 18.5-60.2 kg/m2. REE was measured by indirect calorimetry in fasting conditions and body composition by bioelectrical impedance. Regression models were used to evaluate age-related changes in REE in subjects stratified by sex and BMI. Models were adjusted for body composition (fat mass, fat free mass), smoking, disease count and physical activity. Results In unadjusted models, the rate of decline in REE was highest in obese men (slope = -8.7 ± 0.8 kcal/day/year) whereas the lowest rate of decline was observed in normal weight women (-2.9 ± 0.3 kcal/day/year). Gender differences were observed for the age of onset of REE adaptive changes (i.e., not accounted by age related changes in body composition and lifestyle factors). In women, adaptive changes appeared to occur in middle-age (∼47 y) across all BMI groups whereas changes seemed to be delayed in obese men (∼54 y) compared to overweight (∼43 y) and normal weight (∼39 y) men. Conclusions Sex and BMI influenced the rate and degree of the age-related decline in REE. Critical age windows have been identified for the onset of putative mechanisms of energy adaptation. These findings require confirmation in prospective studies.