TY - JOUR T1 - Insights into mortality patterns and causes of death through a process point of view JF - bioRxiv DO - 10.1101/067967 SP - 067967 AU - James J. Anderson AU - Ting Li AU - David J. Sharrow Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/05/067967.abstract N2 - Process point of view models of mortality such as the Strehler-Mildvan-Gompertz and stochastic vitality models, represent death in terms of abstract loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these abstract concepts to candidate biological mechanisms through a framework that partitions causes of death into distal and proximal components. Hypothesizing that the immune system is a mortality nexus, we define distal components for juvenile immune system development and adult immunosenescence. Immune system disruption by proximal components defines three cause-of-death classes: juvenile extrinsic mortality and adult extrinsic mortality result from extrinsic disease and stress challenges to the juvenile and adult stages of the immune system, and adult intrinsic mortality results from the exhaustion of the adult immune system by immunosenescence. Patterns of model parameters, generated from Swedish mortality data (1751–2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The 20th century epidemiological transition in mortality is characterized by the proximal component shifting from infectious disease challenges to physical exertion challenges. The distal component change, involving slow improvements in immune system function, was of secondary importance. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed. Finally, our intent is to demonstrate that new insights into historical and future patterns of mortality can be gained through a process point of view. ER -