Figure 1.

Schematic representation of 12 types of sufficient causes for aging-related diseases and intrinsic mortality using “causal pies.” Usually in this kind of representation of the sufficient and component causes model of causation, a pie represents a sufficient cause and the slices in each pie represent specific component causes, which can be a genetic or an environmental factor. A given genetic or environmental component cause can be shared by two or more sufficient causes. Here, under the evolution-based model of causation, the slices represent categories of component causes and the presence of a category of component cause in a sufficient cause means that one or more genetic effects or environmental factors of that category are part of the sufficient cause. Moreover, genetic and environmental component causes are considered to occur as random events following time-to-event distributions. Aging-related diseases are taken to involve at least hundreds of sufficient causes, as currently supported for cancer (30) and neurodegenerative disease (31); a monogenic form of an aging-related disease corresponds to a sufficient cause containing only one LOGE. ECEF, evolutionarily conserved environmental factor(s); EOGE, early-onset genetic effect(s); EREF, evolutionarily recent environmental factor(s); LOGE, late-onset genetic effect(s) [reproduced from Levy and Levin (1)].