Damage-Fitness Model: the missing piece in integrative stress models.

Over the last decade, several theoretical models have been put forth to describe how animals respond to adverse environments and how this response changes under different physiological demands across life history stages. These models capture the context- and condition-dependent nature of stress responses. Yet, application of the models has been limited thus far in part because each model addresses different aspects of the problems facing the field of stress biology. Thus, there is a need for a unifying theoretical model that incorporates changes in physiological demand with life history stages and age, intricate relationships among physiological systems, and biphasic nature of stress responses. Here, I propose a new integrative framework, the Damage-Fitness Model. In this model, regulators, such as DNA repair mechanisms and glucocorticoids, work together as anti-damage mechanisms to minimize damage at both the cellular and organismal level. When the anti-damage regulators are insufficient or inappropriate, persistent damage accumulates. Previous studies indicate that these damage directly impact reproductive performance, disease risk, and survival. The types of regulators, the threshold at which they are initiated, and the magnitude of the responses are shaped by developmental and current environments. This model unites existing theoretical models by shifting our focus from physiological responses to downstream consequences of the stress responses, circumventing context specificity. Discussions include (1) how the proposed model relates to existing models, (2) steps to test the new model, and (3) how this model can be used to better assess the health of individuals and a population.