Why organisms age and the reasons for the differences in longevity between different species is a fundamental question in biology. Changes in aging rates can be induced, most notably by increasing or decreasing calorie intake: Organisms subjected to caloric restriction (CR) live longer compared to those fed ad libitum (AL). CR robustly affects the age-related changes of several pathways: gene expression, hormones, oxidative damage, immune system, etc. All these mechanisms have a remarkable effect on longevity. Here we suggest why understanding these mechanisms in an integrated way is in the interest of all aging research fields and the SENS strategy.