Allostasis and Allostatic Overload in the Context of Aging

Introduction

“Stress” is often identified as a factor in accelerated aging, an important factor in disorders such as cardiovascular disease and depression, and a contributor to other disorders. Being “stressed out” is a commonly used expression that generally refers to experiences that cause feelings of anxiety, anger, and frustration because they push a person beyond his or her ability to successfully cope. Besides time pressures and daily hassles at work and home, there are stressors related to economic insecurity, poor health, and interpersonal conflict. More rarely, there are situations that are life-threatening (e.g., accidents, natural disasters, violence), and these evoke the classic “fight or flight” response. In contrast to daily hassles, these stressors are acute and yet they also can lead to depression, anxiety, posttraumatic stress disorder, and other forms of chronic stress in the aftermath of the tragic event.

The most common stressors are, therefore, ones that operate chronically, often at a low level, and cause us to behave in certain ways. For example, being “stressed out” may promote anxiety or depressed mood, poor sleep, eating of comfort foods and overconsumption of calories, smoking, or drinking alcohol excessively. Being stressed out may reduce social interactions or regular physical activity. Not infrequently, anxiolytics and sleep-promoting agents are used, but, with continuation of this state, the body may increase in weight, develop metabolic dysregulation, and build up atherosclerotic plaque.

The brain is the organ that decides what is stressful and determines the behavioral and physiologic responses, whether health promoting or health damaging. The brain is a biologic organ that changes under acute and chronic stress and directs many systems of the body (metabolic, cardiovascular, immune, renal) that are involved in the short- and long-term consequences of being stressed out.

What does chronic stress do to the body and brain, particularly in relation to the aging process? This chapter summarizes some of the current information, emphasizing how the stress hormones and related mediators can play both protective and damaging roles in the brain and body, depending on how tightly their release is regulated. The chapter also discusses some of the approaches for dealing with stress in a complex world.

Definition of Stress, Allostasis, and Allostatic Load and Overload

Stress is an ambiguous term and the actual stress response has protective, as well as potentially damaging, effects. On the one hand, the body responds to almost any novel or challenging event by releasing catecholamines that increase heart rate and blood pressure and help adapt to the situation. Yet, chronically increased heart rate and blood pressure produce a chronic wear and tear on the cardiovascular system that can result, over time, in disorders such as atherosclerosis, strokes, and heart attacks. Sterling and Eyer introduced the term allostasis to refer to the active process by which the body responds to daily events and maintains homeostasis (allostasis literally means “achieving stability through change”). Because chronically increased allostasis can lead to disease, we introduced the term allostatic load or overload to refer to the wear and tear that results from either too much stress or from inefficient management of allostasis (e.g., not turning off the response when it is no longer needed). Other states that lead to allostatic overload, a term referring to pathophysiologic consequences, otherwise referred to as “toxic stress,” are summarized in Figure 12-1 and involve not turning on an adequate response in the first place or not habituating to the recurrence of the same stressor, which then fails to dampen the allostatic response.

Protection and Damage as the Two Sides of the Response to Stressors

Protection and damage are the two contrasting sides of the physiology that defend the body against the challenges of daily life, whether or not we call them “stressors.” In addition to epinephrine and norepinephrine, many other mediators participate in allostasis, and they are linked together in a network of regulation that is nonlinear ( Figure 12-2 ), meaning that each mediator has the ability to regulate the activity of the other mediators, sometimes in a biphasic manner. Glucocorticoids are the other major “stress hormones.” Proinflammatory and antiinflammatory cytokines are produced by many cells in the body, and they regulate each other and are, in turn, regulated by glucocorticoids and catecholamines. Whereas catecholamines can increase proinflammatory cytokine production, glucocorticoids are known to inhibit this production. The parasympathetic nervous system also plays an important regulatory role in this nonlinear network of allostasis, since it generally opposes the sympathetic nervous system and, for example, slows the heart and also has antiinflammatory effects.

What this nonlinearity means is that when any one mediator is increased or decreased, there are compensatory changes in the other mediators that depend on time course and level of change of each of the mediators. Unfortunately, we cannot measure all components of this system simultaneously and must rely on measurements of only a few of them in any one study. Yet the nonlinearity must be kept in mind in interpreting the results.