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Resilience, Stress, and the Neurobiology of Aging: Page 2 of 4

Resilience, Stress, and the Neurobiology of Aging: Page 2 of 4

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.

Temperament appears to be one of the determinants of resilience that is, at least, partially heritable. Protective temperamental factors include sociability, intelligence, social competence, internal locus of control, warmth and closeness of affectional ties, and active emotional support within the family network or within religious groups.25 As such, resilience may represent an important target for treatment and prevention of anxiety, depression, and abnormal stress reactions in aging persons (Figure).

Well-being and aging

A sense of well-being is an important characteristic of successful aging. Ryff and colleagues26 described 2 types of well-being: eudaimonic and hedonic. The aristotelian concept of eudaimonic well-being addresses ideas of self-development and self-acceptance, personal growth, positive relationships, and purposeful engagement. Hedonic well-being is concerned with positive feelings, such as happiness and contentment.

A sense of ill-being refers to all negative affect states, such as depression and anxiety. Different biological markers, including neuroendocrine (cortisol, epinephrine, norepinephrine), immune (IL-6, vaccine antibody response), cardiovascular (blood pressure, waist-hip ratio, cholesterol, glycosylated hemoglobin), sleep (duration/latency of rapid eye movement), and neural circuitry (cerebral asymmetry), are associated with the states of well-being or ill-being.26 The question remains whether resilience is responsible for the differences.

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