The ability to appropriately and successfully regulate emotion is a vital component of mental and physical health. Even healthy individuals differ substantially in their reactivity to emotionally relevant events, and in their capacity to regulate negative affect, which changes across the lifespan. Such individual differences are characterised by differences in the recruitment of brain regions underlying emotion regulation, particularly medial areas of prefrontal cortex (PFC) and amygdala, and in their downstream effects on mental processes, physiology, and behaviour. The aim is to study the neural mechanisms that characterise the ability of individuals to respond adaptively to negative events, and how these mechanisms may change across the lifespan. Concretely, we propose to measure activity in the neural circuitry of emotion regulation, while taking an individual’s emotional reactivity into account, in participants from a large age range (20-80 years). Measures of physiological responding to emotional stimuli will allow the assessment of individual variability in emotional reactivity in a first session, and functional brain imaging measures will be acquired in a second session while performing emotion regulation tasks. We predict that individuals who successfully regulate their emotion show patterns of reduced amygdala and increased ventromedial PFC activation. We further predict that brain activation patterns shift across the lifespan from more dorsolateral PFC to medial PFC when participants voluntarily regulate their emotion, and when controlling for emotional reactivity. We also expect that (self-reported) well-being in daily life is predictive of brain activation patterns underlying regulation. Understanding appropriate and successful emotion regulation is an important component of mental and physical health, and understanding how emotion reactivity and regulation changes across the lifespan would help in promoting healthy ageing.