Resilience, Stress, and the Neurobiology of Aging

The aging of the world’s populations represents one of the most remarkable success stories in medicine and of humankind, but it is also a source of various challenges. Getting older can be stressful because of multiple losses (eg, interpersonal, financial) and a decline in health, independence, and cognitive and functional abilities.

Worldwide, human life expectancy has increased steadily for nearly 200 years and this trend is expected to continue. In every decade of the past century, life expectancy increased by about 2 years. This increase was driven in the first decades by improvements in sanitation, housing, and education. A steady decline in early and midlife mortality was mostly the result of our ability to prevent and treat infections. The increase in life expectancy in the latter half of the century was almost entirely attributable to a decline in late-life mortality secondary to medical advances and improved socioeconomic conditions.¹

Many older adults are living longer with chronic illnesses yet are making the best of their later years. As George E. Vaillant² pointed out in his book Aging Well, “The major factors involved in negative personality change at midlife are the same factors that caused negative aging at 70: bad habits, bad marriage, maladaptive defenses, and disease.”

The benefits of a positive outlook

Empirical evidence now supports the long-held belief that positive emotions are good for one’s health. Fredrickson’s “broaden-and-build theory” shows how positive emotions contribute to psychological and physical well-being through more effective coping.^3,4 It is a natural drive to seek personal happiness and fulfillment regardless of age. Successful aging is associated with a positive psychological outlook in later years, general well-being, and happiness.^2,5-7

With global trends in population aging, many nations are developing and implementing healthy aging policies to promote quality of life and additional years of health.⁷ One direction is to improve resilience to stress.

Depp and Jeste⁶ have defined resilience as “the ability to maintain biological and psychological homeostasis under stress. It may vary with context, time, age, gender, and cultural origin. Inquiry into resilience has evolved from descriptions of resilient qualities to uncovering the process of resilient adaptation. In older adults, resilience has been studied mostly in the context of successful aging (eg, in centenarians) or in the context of recovery from injury or illness.” The question remains whether resilience can be operationalized and taught to older stressed individuals and whether any interventions exist that boost resilience to stress and life’s adversities.

 

CHECKPOINTS

• Human responsiveness to stress may be attenuated by learned or adaptive skills, retraining, or increased resilience to future stress
• Physiological mediators such as adrenaline from the adrenal medulla, glucocorticoids from the adrenal cortex, and cytokines from the cells of the immune system act on receptors in various tissues and organs to produce effects that are adaptive to stress in the short run but can be damaging if the mediators are not shut off when no longer needed
• Prospective determinants of resilience for future studies include neuroendocrine, immunological, neural, genetic, temperamental, and environmental influences.

 

Stress and aging

Selye⁸ coined the term “stress” to define the alarm reaction, the stage of resistance, and the stage of exhaustion in animals and in humans. Only when the subject is overwhelmed or derailed does the stress response system begin to cause disease.⁹ Exposure to stress can be characterized in several ways: duration (acute, chronic), responsiveness (adaptive, hyperadaptive, nonresponsive), and severity (mild, moderate, extreme).¹⁰

Human responsiveness to stress may be attenuated by learned or adaptive skills, retraining, or indifference to future stress. The hypothalamic-pituitary-adrenal axis can be up regulated by a stressful experience, with increased amounts of circulating glucocorticoids, catecholamines, serotonin, and cytokines. These acute responses can lead to pathological changes that may be amplified by the aging of the brain.¹⁰

The adaptive physiological response to acute stress that involves internal milieu adjustment to change in the environment was initially described by Sterling and Eyer.¹¹ McEwen¹² extended this definition to include the concept of a set point that changes because of the process of maintaining homeostasis in the body that is mediated by the neuroendocrine, autonomic nervous, and immune systems. Allostasis is the term used to describe this process of “maintaining stability through change.”

Physiological mediators such as adrenaline from the adrenal medulla, glucocorticoids from the adrenal cortex, and cytokines from the cells of the immune system act on receptors in various tissues and organs to produce effects that are adaptive in the short run. If the mediators are not shut off when no longer needed, they can lead to deleterious effects of chronic stress, including receptor desensitization and tissue damage.

Aging can contribute to poor responsivity to stress because of reduced resilience.¹³ Accumulation of wear and tear caused by daily experiences and major life stressors can interact with genetic constitution and predisposing early life experiences to produce individual differences in the age-related diseases.^10,13,14

Immunity, inflammation, and aging

The plasma concentrations of inflammatory mediators, such as cytokines and acute phase proteins, increase with aging, which results in low-grade inflammation. These changes lead to increased obesity and adiposity; a decrease in production of sex steroids; subclinical infections; and chronic aging-related disorders, such as cardiovascular disease and arthritis. Furthermore, aging is associated with a dysregulated cytokine response following stimulation.¹⁵

Several inflammatory mediators, such as tumor necrosis factor-α and interleukin-6 (IL-6), have the potential to induce and/or aggravate risk factors in age-associated pathology. Inflammatory mediators are also strong predictors of mortality independent of other known risk factors in elderly cohorts. For example, a proinflammatory factor IL-6 has been linked with Alzheimer disease, osteoporosis, rheumatoid arthritis, cardiovascular disease, and some forms of cancer, and it has been prospectively associated with general disability and mortality in large population-based studies.^16-21

Neural circuitry and resilience

Brain imaging promotes understanding of brain regulation of positive emotions and resilience.²² The brain circuitry that is involved in emotional regulation includes several areas of the prefrontal cortex (PFC), amygdala, hippocampus, and anterior cingulate. The PFC plays a crucial role in the anticipation of future affective consequences of action as well as in the persistence of emotion.²²

There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays a different role in emotional regulation. The amygdala appears to be crucial for learning new stimulus-threat contingencies and to be important in the expression of cue-specific fear.²³ Tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Asymmetries within the PFC and activation of the amygdala are responsible for individual differences in affective style.^22,23 Plasticity in this circuitry has implica-tions for cultivating positive affect and resilience.^22,23

Resilience and aging

A coherent pattern of individual characteristics associated with resilience and successful adaptation has emerged. Salient characteristics include commitment, dynamism, humor in the face of adversity, patience, optimism, faith, and altruism.²⁴ There are emotional and cognitive aspects of resilience that can be innate or learned. The innate affective or emotional styles that are likely to influence resilience refer to the individual styles of affect regulation, which are usually a part of personality structure (eg, optimism or pessimism), or social intelligence.

Internal server error