Composite estimates of physiological stress, age, and diabetes in American Samoans

Composite estimates of physiological stress such as allostatic load (AL) were developed to help assess cumulative impacts of psychosocial and physical stressors on the body. Physiological responses to stress generally accelerate somatic wear-and-tear and chronic degenerative conditions (CDCs). Following McEwen (Neuropsychopharmacology 22 (1999) 108-124) and others, primary physiological mediators of somatic stress responses include glucocorticoids (cortisol), catecholamines (adrenaline and noradrenaline), and serum dihydroepiandosterone-sulfate (DHEA-S). Conversely, blood pressure (BP), serum HDL and total cholesterol, glycated hemoglobin (HbA1c), and waist/hip (w/h) ratio are modulated by such hormones, thereby acting as secondary mediators of stress response. When these risk factors are aggregated into a composite score, higher stress loads are associated with increased risks for days of school/work missed, functional losses, morbidity, and mortality in US samples. To examine stress loads in American Samoans, data on all 6 secondary mediators along with estimates of body habitus (i.e. height, weight, circumferences, skinfolds) and physiology (i.e. fasting insulin, LDLc, triglycerides, fasting glucose) were measured on 273 individuals residing on Tutuila Island in 1992. Four combinations of these physiological factors were used to determine composite estimates of stress. These were then assessed by sex for associations with age and the presence of diabetes. Composite estimates of stress load were higher in Samoan women than men. Associations with age tended to be low and negative in men, but positive in women, appearing to reflect cultural circumstances and population history. Stress load scores also were higher among those with diabetes than those without among both men and women. These results suggest that composite estimates of stress may be useful for assessing future risks of CDC's and the senescent processes that may underlie them in cross-cultural research.     

The detrimental effects of allostasis: allostatic load as a measure of cumulative stress

Since its inception in the 1980s, through further developments during the 1990s, and continuing today, the paradigm of allostatic load (AL) has becomed an important paradigm for predicting senescence and mortality. AL is a cumulative measure of the effects of multiple stressors and the process of responding to stressors on the soma. AL measurements of individuals is being tested on various samples and species and being reported across a variety of medical and social science journals. From the ISI Web of Science, all articles published between January 2000 and June 2005 with AL in any default category were obtained and transferred to Endnote. These articles, categorized as theory/review or data-driven, human or animal, and variability in risk factors used to estimate AL, are reviewed here. Only two of 90 reports were published in anthropological journals, likely, at least partly, because research on AL has focused more on western, industrialized populations where data are more easily obtained. From 2000-2005, 12 of 42 data-driven reports focused on elderly humans. Studies of animal models also are common (0 in 2000, but 4 in 2004 covering 21 species). During the last year, multiple additional potential physiological variables have been tested as measures of AL (10 to 20 in any one article). In the past half decade, AL also has been introduced to a wide range of disciplines, including psychology, anthropology, gerontology, veterinary medicine, and medical specialties, as a viable research theme. AL appears to provide a useful method for determining cumulative somatic stress such as that seen with senescence and frailty at older ages.     

The soma-germline communication: implications for somatic and reproductive aging

Aging is characterized by a functional decline in most physiological processes, including alterations in cellular metabolism and defense mechanisms. Increasing evidence suggests that caloric restriction extends longevity and retards age-related diseases at least in part by reducing metabolic rate and oxidative stress in a variety of species, including yeast, worms, flies, and mice. Moreover, recent studies in invertebrates – worms and flies, highlight the intricate interrelation between reproductive longevity and somatic aging (known as disposable soma theory of aging), which appears to be conserved in vertebrates. This review is specifically focused on how the reproductive system modulates somatic aging and vice versa in genetic model systems. Since many signaling pathways governing the aging process are evolutionarily conserved, similar mechanisms may be involved in controlling soma and reproductive aging in vertebrates.     

Sex hormonal regulation and hormesis in aging and longevity: role of vitagenes

Aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones, such as cortisol and thyroid hormones which remain stable and hormones with anabolic effects (testosterone, insulin like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate (DHEAS), that decrease with age. Deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons.Unlike female menopause, which is accompanied by an abrupt and permanent cessation of ovarian function (both folliculogenesis and estradiol production), male aging does not result in either cessation of testosterone production nor infertility. Although the circulating serum testosterone concentration does decline with aging, in most men this decrease is small, resulting in levels that are generally within the normal range. Hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with HT treatment. Stress-response hormesis from a molecular genetic perspective corresponds to the induction by stressors of an adaptive, defensive response, particularly through alteration of gene expression. Increased longevity can be associated with greater resistance to a range of stressors. During aging, a gradual decline in potency of the heat shock response occur and this may prevent repair of protein damage. Conversely, thermal stress or pharmacological agents capable of inducing stress responses, by promoting increased expression of heat-shock proteins, confer protection against denaturation of proteins and restoration of proteome function. If induction of stress resistance increases life span and hormesis induces stress resistance, hormesis most likely result in increased life span. Hormesis describes an adaptive response to continuous cellular stresses, representing a phenomenon where exposure to a mild stressor confers resistance to subsequent, otherwise harmful, conditions of increased stress. This biphasic dose–response relationship, displaying low-dose stimulation and a high-dose inhibition, as adaptive response to detrimental lifestyle factors determines the extent of protection from progression to metabolic diseases such as diabetes and more in general to hormonal dysregulation and age-related pathologies. Integrated responses exist to detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Vitagenes encode for heat shock proteins (Hsps), thioredoxin and sirtuin protein systems. Nutritional antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways under control of Vitagene protein network. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against functional defects leading to degeneration and cell death with consequent impact on longevity processes.     

Assessing Stress in Zoo-Housed Western Lowland Gorillas (<Emphasis Type="Italic">Gorilla gorilla gorilla</Emphasis>) Using Allostatic Load

Stress contributes to the development of chronic degenerative diseases in primates. Allostatic load is an estimate of stress-induced physiological dysregulation based on an index of multiple biomarkers. It has been applied to humans to measure effects of stress and predict health outcomes. Assessing allostatic load in nonhuman primates may aid in understanding factors promoting compromised health and longevity in captive populations, as well as risk assessment among wild populations following human activities. We applied an allostatic load index to gorillas housed at the Columbus Zoo and Aquarium (N = 27, 1956–2014) using data from medical records and biomarkers from banked serum. We estimated allostatic load using seven biomarkers (albumin, cortisol, corticotropin-releasing hormone, dehydroepiandrosterone sulfate, glucose, interleukin-6, and tumor necrosis factor alpha) and then examined this index for associations with age, sex, number of stressful events, parturition, physiological health measures, and age at death. Stressful events were defined as agonistic interactions with wounding, translocations, and anesthetizations. Allostatic load positively associated with age and total number of lifetime stressful events. Allostatic load was significantly higher in females than in males. Allostatic load was not associated with number of pregnancies and was not different between nulliparous and parous females. Allostatic load associated positively with serum creatinine and triglyceride levels, showed a nonsignificant negative association with cholesterol, and did not associate significantly with age at death. These results demonstrate the potential utility of allostatic load for exploring long-term stress and health risks, as well as for evaluating environmental stressors for gorillas and other nonhuman primates in captivity and in the wild.     

哺乳动物的生理应激反应及其生态适应性

应激反应是哺乳动物的基本生理现象之一。目前,与应激有关的研究主要来自生物医学和神经内分泌学。虽然Hans Selye 提出了个体对应激的普遍性适应综合症概念,但目前的研究还主要集中于应激对个体的负效应以及与应激相关的疾病研究。然而,从进化角度似乎很难理解在数亿年的进化过程中,动物应激反应仅简单地
进化为影响个体健康并导致个体患病的一种生理过程。本文从进化的角度,综述了应激反应与动物繁殖对策的关系以及个体对环境应激源的应对类型,并阐述了动物应激反应的适应和进化意义。     

Stress and demographic decline: a potential effect mediated by impairment of reproduction and immune function in cyclic vole populations

The stress response is initially adaptive, operating to maintain homeostasis. However, chronic long-term exposure to stressors may have detrimental effects. We proposed that chronic stress may be a major factor in demographic vole cycles, inducing decline in high-density populations. We monitored four populations of the fossorial water vole Arvicola scherman, which undergo pluriannual demographic cycles in the Jura Mountains (France). Sampling was conducted during the high densities and the decline. We measured fecal corticosterone metabolites (FCMs) to assess stress levels and injected phytohemagglutinin to estimate the cell-mediated immune response. We demonstrated that stress levels increase between the high densities and the decline in most of the vole populations. At the individual level, FCM concentrations varied with reproductive status and body condition. During the outbreak, we observed significantly higher levels of FCM concentrations in nulliparous females than in females that had previously reproduced. Moreover, a significant negative correlation was observed between concentrations of FCMs and both immunocompetence and body condition during population decline. These results might reflect an impairment of the female reproductive capability in high densities and accelerated senescence affecting immune function during decline, both arising from chronic stress.     

Cell resilience in species life spans: a link to inflammation?

Species differences in life span have been attributed to cellular survival during various stressors, designated here as ‘cell resilience’. In primary fibroblast cultures, cell resilience during exposure to free radicals, hypoglycemia, hyperthermia, and various toxins has shown generally consistent correlations with the species characteristic life spans of birds and mammals. However, the mechanistic links of cell resilience in fibroblast cultures to different species life spans are poorly understood. We propose that certain experimental stressors are relevant to somatic damage in vivo during inflammatory responses of innate immunity, particularly, resistance to reactive oxygen species (ROS), low glucose, and hyperthermia. According to this hypothesis, somatic cell resilience determines species differences in longevity during repeated infections and traumatic injuries in the natural environment. Infections and injury expose local fibroblasts and other cells to ROS generated by macrophages and to local temperature elevations. Systemically, acute phase immune reactions cause hypoglycemia and hyperthermia. We propose that cell resilience to somatic stressors incurred in inflammation is important in the evolution of longevity and that longer‐lived species are specifically more resistant to immune‐related stressors. This hypothesis further specifies Kirkwood’s disposable soma theory. We suggest expanding the battery of stressors and markers used for comparative studies to additional cell types and additional parameters relevant to host defense and to their ecological specificities.     

Testing local and global stressor impacts on a coastal foundation species using an ecologically realistic framework

Despite the abundance of literature on organismal responses to multiple environmental stressors, most studies have not matched the timing of experimental manipulations with the temporal pattern of stressors in nature. We test the interactive effects of diel‐cycling hypoxia with both warming and decreased salinities using ecologically realistic exposures. Surprisingly, we found no evidence of negative synergistic effects on Olympia oyster growth; rather, we found only additive and opposing effects of hypoxia (detrimental) and warming (beneficial). We suspect that diel‐cycling provided a temporal refuge that allowed physiological compensation. We also tested for latent effects of warming and hypoxia to low‐salinity tolerance using a seasonal delay between stressor events. However, we did not find a latent effect, rather a threshold survival response to low salinity that was independent of early life‐history exposure to warming or hypoxia. The absence of synergism is likely the result of stressor treatments that mirror the natural timing of environmental stressors. We provide environmental context for laboratory experimental data by examining field time series environmental data from four North American west coast estuaries and find heterogeneous environmental signals that characterize each estuary, suggesting that the potential stressor exposure to oysters will drastically differ over moderate spatial scales. This heterogeneity implies that efforts to conserve and restore oysters will require an adaptive approach that incorporates knowledge of local conditions. We conclude that studies of multiple environmental stressors can be greatly improved by integrating ecologically realistic exposure and timing of stressors found in nature with organismal life‐history traits.     

Telomere length reveals cumulative individual and transgenerational inbreeding effects in a passerine bird

Inbreeding results in more homozygous offspring that should suffer reduced fitness, but it can be difficult to quantify these costs for several reasons. First, inbreeding depression may vary with ecological or physiological stress and only be detectable over long time periods. Second, parental homozygosity may indirectly affect offspring fitness, thus confounding analyses that consider offspring homozygosity alone. Finally, measurement of inbreeding coefficients, survival and reproductive success may often be too crude to detect inbreeding costs in wild populations. Telomere length provides a more precise measure of somatic costs, predicts survival in many species and should reflect differences in somatic condition that result from varying ability to cope with environmental stressors. We studied relative telomere length in a wild population of Seychelles warblers (Acrocephalus sechellensis) to assess the lifelong relationship between individual homozygosity, which reflects genome‐wide inbreeding in this species, and telomere length. In juveniles, individual homozygosity was negatively associated with telomere length in poor seasons. In adults, individual homozygosity was consistently negatively related to telomere length, suggesting the accumulation of inbreeding depression during life. Maternal homozygosity also negatively predicted offspring telomere length. Our results show that somatic inbreeding costs are environmentally dependent at certain life stages but may accumulate throughout life.     

Each meal matters in the exposome: Biological and community considerations in fast-food-socioeconomic associations

Advances in omics and microbiome technology have transformed the ways in which the biological consequences of life in the ‘ecological theatre' can be visualized. Exposome science examines the total accumulated environmental exposures (both detrimental and beneficial) as a means to understand the response of the ‘total organism to the total environment' over time. The repetitive stimulation of compensatory physiological responses (immune, cardiovascular, neuroendocrine) in response to stress – including sources of stress highly relevant to socioeconomic disadvantage – may lead to metabolic dysregulation and cellular damage, ultimately influencing behavior and disease. The collective toll of physiological wear and tear, known as allostatic load, is not paid equally throughout developed societies. It is paid in excess by the disadvantaged. In the context of fast-food, human and experimental research demonstrates that the biological response to a single fast-food-style meal – especially as mediated by the microbiome- is a product of the person's total lived experience, including the ability to buffer the fast-food meal-induced promotion of inflammation and oxidative stress. Emerging research indicates that each meal and its nutritional context matters. As we discuss, equal weekly visits to major fast-food outlets by the affluent and deprived do not translate into biological equivalency. Hence, debate concerning reducing fast-food outlets through policy – especially in disadvantaged neighborhoods where they are prevalent – requires a biological context. The fast-food establishment and fast-food meal – as they represent matters of food justice and press upon non-communicable disease risk – are far more than physical structures and collections of carbohydrate, fat, sugar and sodium.     

Evolutionary and Ecological Effects of Multi-Generational Exposures to Anthropogenic Stressors

Biological and ecological responses to stress are dictated by duration and frequency, as well as instantaneous magnitude. Conditional compensatory responses at the physiological and behavioral levels, referred to as ‘acclimation’, may mitigate effects on individuals experiencing brief or infrequent periods of moderate stress. However, even modest stress over extended periods may reduce the fitness of some or all exposed individuals. In this way, specific stress that persists over multiple generations will increase probabilities for extinction of populations composed of sensitive individuals. For populations whose members demonstrate variance and heritability for stressor response, this selective loss of sensitive individuals may result in populations dominated by resistant individuals. The formation of these ‘adapted’ populations may be considered an ecological compensatory mechanism to multi-generational stress. Paradoxically, the biological costs to individuals of toxicity and physiological acclimation may result in obvious signs of stress in affected wildlife populations while the costs of genetic adaptation may be more covert. It is important to consider such costs because recent evidence suggests that anthropogenic stressors have acted as powerful selection agents that have modified the composition of wildlife populations subjected for successive generational exposures to specific stressors. This essay focuses on a case study where adaptation has been demonstrated in fish populations with a history of chronic exposure to persistent, bioaccumulative and toxic environmental contaminants. Because the magnitude, breadth and long-term outcomes of such changes are unknown, ecological risk assessments that are limited in focus to short-term exposures and consequences may seriously underestimate the ecological and evolutionary impacts of anthropogenic stressors.     

Boldness behavior and stress physiology in a novel urban environment suggest rapid correlated evolutionary adaptation

Novel or changing environments expose animals to diverse stressors that likely require coordinated hormonal and behavioral adaptations. Predicted adaptations to urban environments include attenuated physiological responses to stressors and bolder exploratory behaviors, but few studies to date have evaluated the impact of urban life on codivergence of these hormonal and behavioral traits in natural systems. Here, we demonstrate rapid adaptive shifts in both stress physiology and correlated boldness behaviors in a songbird, the dark-eyed junco, following its colonization of a novel urban environment. We compared elevation in corticosterone (CORT) in response to handling and flight initiation distances in birds from a recently established urban population in San Diego, California to birds from a nearby wildland population in the species' ancestral montane breeding range. We also measured CORT and exploratory behavior in birds raised from early life in a captive common garden study. We found persistent population differences for both reduced CORT responses and bolder exploratory behavior in birds from the colonist population, as well as significant negative covariation between maximum CORT and exploratory behavior. Although early developmental effects cannot be ruled out, these results suggest contemporary adaptive evolution of correlated hormonal and behavioral traits associated with colonization of an urban habitat.     

Homeostatic dysregulation proceeds in parallel in multiple physiological systems

An increasing number of aging researchers believes that multi‐system physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi‐system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary ‘systems’ generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi‐system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system‐specific processes likely linked through weak feedback effects. These processes – probably many more than the six measured here – are implicated in aging.     

Cardiac Coherence Training to Reduce Anxiety in Remitted Schizophrenia,a Pilot Study

Health care that addresses the emotional regulation capacity of patients with schizophrenia confronted with daily stress may contribute to a less anxious life. A psycho-physiological training [cardiac coherence training (CCT)] focusing on emotion regulation is known to decrease anxiety for healthy individuals. We performed a pilot cross sectional survey to explore the benefits of CCT for clinically stable patients with schizophrenia. Ten patients were enrolled in the program consisting of twelve weekly 1-h session programs monitored over a 2-month period. Standardised questionnaires were used before and after the intervention to assess anxiety, well-being outcomes, and how patients deal with stress and stressors. Results showed that this quite-well accepted intervention improved (or tended to improve) well-being outcomes, state-anxiety, and emotional stressors evaluation. The successful transformations were higher for patients with the highest clinical and emotional suffering. Thus, this pilot study revealed that CCT may help patients with schizophrenia to deal with anxiety in daily life.     

Phylogeny of the neuroendocrine-immune system: Fish and shellfish as model systems for social interaction stress research in humans

Significant interactions among various physiological systems and between an organism's physiological and psychological structures are evident throughout phylogeny. Environmental stimuli induce neuroendocrine responses that include the activation of the sympathetic nervous system and of the hypothalamic-pituitary-adrenal (HPA) axis, and that modulate cellular and humoral host defense mechanisms from the invertebrates to humans. Because increased levels of HPA products are among the most consistent physiological responses to stress, and bacause cell-mediated immune (CMI) mechanisms are crucial to the initiation, propagation, and regulation of antigen-specific immune responses, this review focuses on the phylogeny of HPA-CMI interaction under basal conditions and following stressful stimuli.Research has characterized several paradigms for the study of the physiological outcomes to a variety of stressors. In recent decades, a substantial literature has emerged that describes the neuro-endocrine-immune response to social confrontation in invertebrates and in vertebrates. The social confrontation paradigm provides an ideal model for the elucidation of the phylogeny of the HPA-CMI interactive system to a specific stressful stimulus. We have characterized the neuroendocrine-immune outcomes of social confrontation in fish. Our data help to explain physiological and pathological mechanisms in fish. Implications of this body of knowledge to clinical medicine and aging are discussed.     

Stress of stoicism: Low emotionality and high control lead to increases in allostatic load

The present longitudinal study examined the combined effects of task persistence and negative emotionality (NE) on allostatic load (AL), a physiological indicator of chronic stress. In line with John Henryism theory, we hypothesized that high persistence combined with low NE may be indicative of a high-effort coping style, leading to high arousal of the nervous system and, as a consequence, increased AL. Mothers reported on children’s NE (N = 158, 72 females) at age 9. Persistence was measured at age 9 using a behavioral measure assessing persistence on an impossible task. AL was measured at ages 9 and 17. The AL measure captured hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, cardiovascular, and metabolic activity. Consistent with previous research, persistence protected against high AL in the context of high NE. However, combined with low NE, high behavioral persistence was associated with higher physiological stress. Our results have implications for both clinical and intervention contexts.     

Behavioral and respiratory responses to stressors in multiple populations of three-spined sticklebacks that differ in predation pressure

Individual animals of the same species inhabiting environments which differ in the frequency and magnitude of stressors often exhibit different physiological and behavioral responses to stressors. Here, we compare the respiratory response to confinement stress, and behavioral responses to ecologically relevant challenges among sticklebacks from 11 different populations varying in predation pressure. We found that sticklebacks from high predation populations breathed faster in response to confinement stress and were, on an average, more behaviorally responsive to a pike behind glass compared with sticklebacks from low predation populations. These patterns differ from the results of studies on other species, highlighting the need for a conceptual framework to understand the proximate and ultimate factors shaping variable responses to stressors over developmental and evolutionary time. Moreover, physiological and behavioral responses were integrated with each other, both at the individual and population levels. In general, fish that were more aggressive and bold in the presence of a predator breathed faster, independent of body size. These results are consistent with the growing body of evidence that individuals differ in a suite of physiological and behavioral mechanisms for coping with challenges in the environment.