An Evolution-Based Model of Causation for Aging-Related Diseases and Intrinsic Mortality: Explanatory Properties and Implications for Healthy Aging.

Aging-related diseases are the most prevalent diseases in advanced countries nowadays, accounting for a substantial proportion of mortality. We describe the explanatory properties of an evolution-based model of causation (EBMC) applicable to aging-related diseases and intrinsic mortality. The EBMC takes the sufficient and component causes model of causation as a starting point and develops it using evolutionary and statistical theories. Genetic component causes are classified as "early-onset" or "late-onset" and environmental component causes as "evolutionarily conserved" or "evolutionarily recent." Genetic and environmental component causes are considered to occur as random events following time-to-event distributions, and sufficient causes are classified according to whether or not their time-to-event distributions are "molded" by the declining force of natural selection with increasing age. We obtain for each of these two groups different time-to-event distributions for disease incidence or intrinsic mortality asymptotically (i.e., for a large number of sufficient causes). The EBMC provides explanations for observations about aging-related diseases concerning the penetrance of genetic risk variants, the age of onset of monogenic vs. sporadic forms, the meaning of "age as a risk factor," the relation between frequency and age of onset, and the emergence of diseases associated with the modern Western lifestyle. The EBMC also provides an explanation of the Gompertz mortality model at the fundamental level of genetic causes and involving evolutionary biology. Implications for healthy aging are examined under the scenarios of health promotion and postponed aging. Most importantly from a public health standpoint, the EBMC implies that primary prevention through changes in lifestyle and reduction of environmental exposures is paramount in promoting healthy aging.