Puzzles in modern biology. III. Two kinds of causality in age-related disease

TL;DR

This paper discusses two fundamental causal dimensions—rate and function—in age-related diseases, illustrating their interplay with examples from cancer to clarify disease mechanisms and guide research.

Contribution

It introduces the rate-function duality concept, providing a framework to understand causality in age-related diseases and resolving longstanding puzzles.

Findings

Causal factors can influence disease onset rate or physiological function independently.

Cancer exemplifies the duality through mutation-driven rate processes and functional invasion mechanisms.

Principles derived from cancer may apply broadly to other age-related diseases.

Abstract

The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease.