Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with ...tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type–specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.
•Social, behavioral and psychological drivers of aging are an important part of geroscience.•Toxic stress accelerates biological aging processes whereas hormetic stress can slow aging, particularly ...due to the salutary actions during recovery from stress.•The types, timing, and frequency of hormetic stress, especially in humans, needs to be better delineated in order to be useful.•Stress resilience, an umbrella term including hormetic stress, can be measured across cellular, physiological, psychosocial functioning.•Developing a deeper understanding of stress resilience will lead to more targeted innovative interventions.
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.
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•The flow of energy is the determining factor between life and death.•Mitochondria sustain life and allostasis via energy transformation and signaling.•Molecular, cellular, and ...behavioral responses to stress increase energy demand.•Mitochondria produce hormones – mitokines – that influence stress physiology.•Research is needed to define the role of mitochondria in human stress responses.
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.
Leukocyte telomere length (LTL) is a putative biological marker of immune system age, and there are demonstrated associations between LTL and cardiovascular disease. This may be due in part to the ...relationship of LTL with other biomarkers associated with cardiovascular disease risk. However, the strength of associations between LTL and adiposity, metabolic, proinflammatory, and cardiovascular biomarkers has not been systematically evaluated in a United States nationally representative population.
We examined associations between LTL and 17 cardiovascular biomarkers, including lipoproteins, blood sugar, circulatory pressure, proinflammatory markers, kidney function, and adiposity measures, in adults ages 20 to 84 from the cross-sectional US nationally representative 1999-2002 National Health and Nutrition Examination Survey (NHANES) (n = 7,252), statistically adjusting for immune cell type distributions. We also examine whether these associations differed systematically by age, race/ethnicity, gender, education, and income. We found that a one unit difference in the following biomarkers were associated with kilobase pair differences in LTL: BMI -0.00478 (95% CI -0.00749--0.00206), waist circumference -0.00211 (95% CI -0.00325--0.000969), percentage of body fat -0.00516 (95% CI -0.00761--0.0027), high density lipoprotein (HDL) cholesterol 0.00179 (95% CI 0.000571-0.00301), triglycerides -0.000285 (95% CI -0.000555--0.0000158), pulse rate -0.00194 (95% CI -0.00317--0.000705), C-reactive protein -0.0363 (95% CI 0.0601--0.0124), cystatin C -0.0391 (95% CI -0.0772--0.00107). When using clinical cut-points we additionally found associations between LTL and insulin resistance -0.0412 (95% CI -0.0685--0.0139), systolic blood pressure 0.0455 (95% CI 0.00137-0.0897), and diastolic blood pressure -0.0674 (95% CI -0.126--0.00889). These associations were 10%-15% greater without controlling for leukocyte cell types. There were very few differences in the associations by age, race/ethnicity, gender, education, or income. Our findings are relevant to the relationships between these cardiovascular biomarkers in the general population but not to cardiovascular disease as a clinical outcome.
LTL is most strongly associated with adiposity, but is also associated with biomarkers across several physiological systems. LTL may thus be a predictor of cardiovascular disease through its association with multiple risk factors that are physiologically correlated with risk for development of cardiovascular disease. Our results are consistent with LTL being a biomarker of cardiovascular aging through established physiological mechanisms.
Chronic stress can affect human health through a myriad of behavioral and biochemical pathways. Tauhis review focuses on some key hormonal and metabolic pathways that appear important today. In ...modern society, we are faced with excessive psychological stress, as well as an epidemic of overeating, and the two together appear to have synergistic effects. Chronic stress can lead to overeating, co-elevation of cortisol and insulin, and suppression of certain anabolic hormones. This state of metabolic stress in turn promotes abdominal adiposity. Both the direct stress response and the accumulation of visceral fat can promote a milieu of systemic inflammation and oxidative stress. This biochemical environment appears to be conducive to several cell aging mechanisms, mainly dampening telomerase and leading to telomere length (TL) shortening and cell senescence. Immune cell telomere shortness is linked with many chronic disease states and earlier mortality. In this way, chronic stress may influence a variety of diseases through a biochemical cascade leading to immune cell senescence. Certain psychological temperaments at high risk of this stress cascade (mainly anxiety prone), gene-environment interactions, and potential interventions for interrupting the stress-aging cascade are discussed.
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.
Abstract Food insecurity acts as a chronic stressor independent of poverty. Food-insecure adults may consume more highly palatable foods as a coping mechanism, leading to poorer diet quality and ...increased risks of chronic disease over time. Using data from the 1999-2008 National Health and Nutrition Examination Surveys, this study aimed to examine the cross-sectional differences in dietary intake and diet quality by household food security among 8,129 lower-income adults (≤300% of the federal poverty level). Food insecurity was assessed using the 18-item US Household Food Security Survey Module. Dietary intake was assessed from 24-hour recalls and diet quality was measured using the Healthy Eating Index-2005 and the Alternate Healthy Eating Index-2010. Relative mean differences in dietary outcomes by household food security were estimated using linear regression models, adjusting for sociodemographic characteristics. Lower-income food-insecure adults reported higher consumption of some highly palatable foods, including high-fat dairy products ( P trend<0.0001) and salty snacks ( P trend=0.01) compared with lower-income food-secure adults. Food insecurity was also associated with more sugar-sweetened beverages ( P trend=0.003); more red/processed meat ( P trend=0.005); more nuts, seeds, and legumes ( P trend=0.0006); fewer vegetables ( P trend<0.0001); and fewer sweets and bakery desserts ( P trend=0.0002). No differences were observed for intakes of total energy and macronutrients. Food insecurity was significantly associated with lower Healthy Eating Index-2005 ( P trend<0.0001) and Alternate Healthy Eating Index-2010 scores ( P trend<0.0001). Despite no macronutrient differences, food insecurity was associated with characteristics of poor diet quality known to increase chronic disease risk.
•Stress research is limited by measurement issues and lack of common definitions.•We present a Stress Typology, common language for describing stress measurement.•A transdisciplinary model of stress ...merges epidemiological and psychological perspectives.•Historical stress shapes current psychological and physiological stress reactivity.•We describe the conscious and unconscious features of acute stress processes.
Stress can influence health throughout the lifespan, yet there is little agreement about what types and aspects of stress matter most for human health and disease. This is in part because “stress” is not a monolithic concept but rather, an emergent process that involves interactions between individual and environmental factors, historical and current events, allostatic states, and psychological and physiological reactivity. Many of these processes alone have been labeled as “stress.” Stress science would be further advanced if researchers adopted a common conceptual model that incorporates epidemiological, affective, and psychophysiological perspectives, with more precise language for describing stress measures. We articulate an integrative working model, highlighting how stressor exposures across the life course influence habitual responding and stress reactivity, and how health behaviors interact with stress. We offer a Stress Typology articulating timescales for stress measurement – acute, event-based, daily, and chronic – and more precise language for dimensions of stress measurement.
Despite the prevalence and adverse consequences of prenatal insomnia, a paucity of research is available regarding interventions to improve insomnia symptoms during pregnancy.
To test the efficacy of ...digital cognitive behavioral therapy for insomnia (CBT-I) compared with standard treatment among pregnant women with insomnia symptoms.
This randomized clinical trial enrolled pregnant women from November 23, 2016, to May 22, 2018. Of the 2258 women assessed for eligibility using an online self-report questionnaire, 208 were randomized to receive digital CBT-I (n = 105) or standard treatment (n = 103) for insomnia. Participants were pregnant up to 28 weeks' gestation, and they either had elevated insomnia symptom severity or met the criteria for insomnia caseness as determined by self-report questionnaires. Participants completed outcome measures at 10 weeks (postintervention) and 18 weeks (follow-up) after randomization. All study visits were completed remotely, and the intervention was delivered digitally. Data were analyzed between December 12, 2018, and July 2, 2019.
Digital CBT-I consisted of 6 weekly sessions of approximately 20 minutes each. Standard treatment reflected standard care. Women receiving standard treatment had no limits placed on the receipt of nonstudy treatments, including medication and psychotherapy.
All outcomes were assessed remotely using self-report questionnaires administered via online survey. The primary outcome was the change in insomnia symptom severity (measured by the Insomnia Severity Index) from baseline to postintervention. Secondary outcomes were sleep efficiency and nightly sleep duration (defined by sleep diary), global sleep quality (measured by the Pittsburgh Sleep Quality Index), depressive symptom severity (measured by the Edinburgh Postnatal Depression Scale), and anxiety symptom severity (measured by the Generalized Anxiety Disorder Scale-7). For each outcome, we also examined the change from baseline to follow-up.
The 208 participants had a mean (SD) age of 33.6 (3.7) years and a mean (SD) gestational age of 17.6 (6.3) weeks at baseline. Most of the participants were white (138 66.3%), married or cohabiting (196 94.2%), had a college degree (180 86.5%), and earned $100 000 or more per year (141 67.8%). Women randomized to receive digital CBT-I experienced statistically significantly greater improvements in insomnia symptom severity from baseline to postintervention compared with women randomized to receive standard treatment (time-by-group interaction, difference = -0.36; 95% CI, -0.48 to -0.23; χ2 = 29.8; P < .001; d = -1.03). Improvements from baseline to postintervention for all secondary outcomes, with the exception of sleep duration, were statistically significant. A similar pattern of results was evident for the change from baseline to follow-up.
In this trial, digital CBT was an effective, scalable, safe, and acceptable intervention for improving insomnia symptoms during pregnancy.
ClinicalTrials.gov identifier: NCT02805998.
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