Geroscience offers a counterpoint to the challenged pursuit of curing diseases of aging, by focusing on slowing the biological aging process for extended healthspan earlier in life. Remarkable progress has led this field toward animal trials and the next challenge lies with translation to humans. There is an emerging number of small human trials that can take advantage of new models integrating behavioral and social factors. Understanding dynamic aging mechanisms, given the powerful social determinants of aging (Crimmins, 2020) and human variability and environmental contexts (Moffitt, 2020), will be critical. Behavioral and social factors are intrinsic to aging. Toxic stressors broadly defined can lead to stress-acceleration of aging, either directly impacting aging processes or by shaping poor behavioral health, and underlie the socioeconomic disparities of aging. In contrast, hormetic stressors, acute intermittent stressors of moderate intensity, can produce stress resilience, the ability for quick recovery and possibly rejuvenation of cells and tissues. Although health research usually examines static biomarkers, aging is reflected in dynamic ability to recover from challenges pointing to new interventions and targets for examining mechanisms. A fuller model incorporating stress resilience provides innovative biobehavioral interventions, both for bolstering response to challenges, such as COVID-19, and for improving healthspan.

Telomeres play an important part in aging and show relationships to lifetime adversity, particularly childhood adversity. Meta-analyses demonstrate reliable associations between psychopathology (primarily depression) and shorter telomere length, but the nature of this relationship has not been fully understood. Here, we review and evaluate the evidence for impaired telomere biology as a consequence of psychopathology or as a contributing factor, and the important mediating roles of chronic psychological stress and impaired allostasis. There is evidence for a triadic relationship among stress, telomere shortening, and psychiatric disorders that is positively reinforcing and unfolds across the life course and, possibly, across generations. We review the role of genetics and biobehavioral responses that may contribute to shorter telomere length, as well as the neurobiological impact of impaired levels of telomerase. These complex interrelationships are important to elucidate because they have implications for mental and physical comorbidity and, potentially, for the prevention and treatment of depression.

The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease.

Energy is required to sustain life and enable stress adaptation. At the cellular level, energy is largely derived from mitochondria - unique multifunctional organelles with their own genome. Four main elements connect mitochondria to stress: (1) Energy is required at the molecular, (epi)genetic, cellular, organellar, and systemic levels to sustain components of stress responses; (2) Glucocorticoids and other steroid hormones are produced and metabolized by mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and metabolic stress mediators; and (4) Experimentally manipulating mitochondrial functions alters physiological and behavioral responses to psychological stress. Thus, mitochondria are endocrine organelles that provide both the energy and signals that enable and direct stress adaptation. Neural circuits regulating social behavior - as well as psychopathological processes - are also influenced by mitochondrial energetics. An integrative view of stress as an energy-driven process opens new opportunities to study mechanisms of adaptation and regulation across the lifespan.

STANDFIRST:: Hopelessness and despair threaten health and longevity. We urgently need strategies to counteract these effects and improve population health. Prosociality contributes to better mental and physical health for individuals, and for the communities in which they live. We propose that prosociality should be a public health priority. COMMENT:: The COVID-19 pandemic produced high levels of stress, loneliness, and mental health problems, magnifying global trends in health disparities. Hopelessness and despair are growing problems particularly in the U.S. The sharp increase in rates of poor mental health is problematic in its own right, but poor mental health also contributes to greater morbidity and mortality. Without action, we will see steep declines in global population health and related costs to society. An approach that is “more of the same” is insufficient to stem the cascading effects of emotional ill-being. Something new is desperately needed. To this point, recent work called on the discipline of psychiatry to contribute more meaningfully to the deaths of despair framework (i.e., conceptualizing rises in suicide, drug poisoning and alcoholic liver disease as due to misery of difficult social and economic circumstances). Recognizing that simply expanding mental health services cannot address the problem, the authors noted the importance of population-level prevention and targeting macro-level causes for intervention. This requires identifying upstream factors causally related to these deaths. However, factors explaining population health trends are poorly delineated and focus on risks and deficits (e.g., adverse childhood experiences, unemployment). A ‘deficit-based’ approach has limits as the absence of a risk factor does not inevitably indicate presence of a protective asset; we also need an ‘asset-based’ approach to understanding more comprehensively the forces that shape good health and buffer harmful effects of stress and adversity.

To combat the obesity epidemic, interventions and treatments often recommend low-calorie dieting. Calorie restriction (CR) as a weight intervention, however, is often unsuccessful, as most people cannot sustain the behavior. Yet one small group has maintained extreme CR over years - members of the CR Society and followers of The CR Way. This study examined stable psychosocial characteristics of these individuals to identify traits that may promote success at long-term CR. In 65 participants, we measured diet, eating behaviors, and personality traits comparing calorie restrictors with two age-, gender-, ethnicity-, and education-matched comparison groups (normal weight and overweight/obese). We first tested whether the CR group restricted calories without indications of eating disorder pathology, and second, what crystallized psychosocial characteristics set them apart from their nonrestricting comparisons. Results indicated the CR group averaged 10 years of CR but scored lower than comparison groups on measures of disordered eating (p < .001) and psychopathology (p < .001). Particularly against overweight/obese participants, CR participants scored lower on neuroticism (p < .04) and hostility (p < .01), and were stronger in future time orientation (p < .05). Overall, CR profiles reflected high self-control and well being, except for having few close relationships. This study suggests a potential predisposition for successful long-term CR without disordered eating. Since modifying trait factors may be unrealistic, there may be psychosocial boundaries to the capacity for sustaining CR. Paralleling a movement toward personalized medicine, this study points toward a personalized behavioral medicine model in behavioral nutrition and treatment of overweight/obesity.

Sleep disturbance is a key behavioral risk factor for chronic medical conditions observed at high rates among overweight and obese individuals. Systemic inflammation, including that induced by stress, may serve as a common biological mechanism linking sleep, adiposity, and disease risk. To investigate these relationships, 48 postmenopausal women (mean age=61.8) completed a standardized laboratory stress task during which time blood was collected at baseline and 30, 50 and 90+ min after stressor onset to assess circulating levels of interleukin (IL)-6, IL-10, and IL-6/IL-10 ratio. Self-reported global sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) while adiposity was estimated by body mass index. Sagittal diameter was obtained in clinic to estimate visceral abdominal adiposity. Multi-level growth curve models revealed that poorer self-reported sleep quality was associated with greater stress-induced increases in IL-6/IL-10 ratio. In terms of adiposity, higher sagittal diameter, but not BMI, was associated with greater IL-6 reactivity (p's<0.05). Further, associations between sleep quality and cytokine reactivity varied as a function of sagittal diameter. Among poor sleepers (1 SD above mean of PSQI score), stress-induced increases in IL-6 and IL-6/IL-10 ratio were significantly steeper in those with high visceral adiposity (1 SD above the mean of sagittal diameter) compared to those with low visceral adiposity (1 SD below the mean of sagittal diameter). In sum, poorer sleep quality and greater visceral adiposity, separately and especially in combination, are associated with greater stress-related increases in systemic inflammation. This research may help elucidate the complex link between sleep, obesity and inflammatory disease risk.

Buddhist philosophy and existing empirical evidence suggest that being engaged in-and accepting-the present moment is associated with greater well-being. However, engaging with the present moment experience and ignoring unwanted thoughts is difficult given the nature of our minds and the competing demands for our attention. This may be especially true when experiencing psychological stress, during which acceptance of current experience may be particularly difficult. This study examines inter- and intraindividual variability in how psychological stress influences daily mind states, and how mind states are related to affect. For 21 days, women (n = 183; half chronically stressed, half low-stress controls) reported levels of mind wandering, engagement with and rejection of their current experience, positive and negative affect, and quality of connection to their partner. Women under chronic stress reported more evening mind wandering, less engagement, and more rejection of the moment, compared to low stress controls. These mind states were in turn associated with more negative evening mood. Daily contextual factors, specifically, having a stressful event (objectively coded) and quality of connection with spouse that day (a known stress buffer), influenced evening mind states. Results provide evidence that chronic and daily psychological stress interfere with daily presence while positive social connection enhances presence in the moment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).