The Arc of Life: a continuous model of the human lifespan for joint-anchored reference intervals

The Arc of Life: a continuous model of the human lifespan for joint-anchored reference intervals Stage models of human life are well established in the clinical, legal and research contexts. The same framework is also used in laboratory medicine, i.e. to measure and to interpret results obtained from human samples. The typical approach to establishing reference intervals (RIs) for test results, however, is to define age-binned RIs for individual tests, even though these RIs are defined for the smooth continua of changes in the physiology of individual analytes with age. Here we discuss a continuous model of the human lifespan, called the Arc of Life, consisting of three lines, i.e. growth and development, mature adulthood and deterioration, connected by fixed and mobile joints of change, and we relate it to the use of continuous reference intervals (CRIs). Evidence from developmental biology, endocrinology and clinical chemistry is provided to support the concept. Furthermore, we review studies that used either indirect data mining or direct paediatric programmes to establish CRIs. We describe the three lines and the six fixed joints of the Arc of Life for males and females, as well as the three mobile joints representing preterm birth, pregnancy and lactation. Importantly, continuous modelling of laboratory analytes already outperforms binned RIs at all childhood transitions. Thus there is a huge potential that has not yet been seized: anchoring these curves at the respective physiological joints of life and extending them to adulthood and old age. The Arc of Life is presented as a hypothesis-generating model that can be tested using existing laboratory information systems.