The restoration of the progressive decline in nicotinamide adenine dinucleotide (NAD+) levels mitigates certain age-associated dysfunctions. A fundamental question is how the NAD+-consuming enzyme CD38 decreases NAD+ levels during ageing. Two new studies by Chini et al. and Covarrubias et al. in this issue of Nature Metabolism show that CD38 expression in macrophages induced by senescence-associated inflammation accounts for the age-related decline in NAD+ levels.