Allostatic load and frailty do not covary significantly among older residents of Greater Poland.

BACKGROUND: Physiological dysregulation/allostatic load and the geriatric syndrome frailty increase with age. As a neurophysiological response system, allostasis supports survival by limiting stressor-related damage. Frailty reflects decreased strength, endurance, and physical abilities secondary to losses of muscle and bone with age. One suggestion, based on large cohort studies of person's ages 70 + years, is that frailty contributes to allostatic load at older ages. However, small community-based research has not confirmed this specific association. METHODS: To further explore possible associations between allostatic load and frailty, we enrolled 211 residents of Greater Poland aged 55-91 years living in a small village (Nekla, N = 104) and an urban center and capital of Greater Poland (Poznan, N = 107). For each, we recorded age, self-reported sex, and residence and estimated a 10-biomarker allostatic load score (ALS) and an 8-biomarker frailty index. We anticipated the following: higher ALS and frailty among men and rural residents; for frailty but not ALS to be higher at older ages; significant associations of ALS with sex and place of residence, but not with age or frailty. The significance of observed associations was evaluated by t-tests and multivariate regression. RESULTS: ALS did not vary significantly between men and women nor between Nekla and Poznan residents overall. However, women showed significantly higher frailty than men. Nekla men showed significantly higher ALS but not frailty, while Nekla women showed nonsignificantly higher ALS and lower frailty than Poznan. In multivariate analyses, neither age, nor sex, nor residence was associated with ALS. Conversely, age, sex, and residence, but not ALS, are associated significantly with frailty. In Nekla, both age and sex, but in Poznan only age, are associated with ALS. Among women, both age and residence, but among men, neither associated with ALS. In no case did ALS associate significantly with frailty. CONCLUSION: In this sample, lifestyle factors associated with residence, age, and sex influence stress-related physiology, less so in women, while ALS and frailty do not covary, suggesting their underlying promoters are distinct. Similar complex associations of physiological dysregulation with frailty, age, sex, and residence likely exist within many local settings. Knowledge of this variation likely will aid in supporting health and healthcare services among seniors.

Allostatic Load in Childhood, Adolescence, and Young Adulthood: Are Assumptions of Measurement Invariance Warranted?

OVERVIEW: Allostatic load represents the cumulative toll of chronic mobilization of the body's stress response systems, as indexed by biomarkers. Higher levels of stress and disadvantage predict higher levels of allostatic load, which, in turn, predict poorer physical and mental health outcomes. To maximize the efficacy of prevention efforts, screening for stress- and disadvantage-associated health conditions must occur before middle age-that is, during childhood, adolescence, and young adulthood. However, this requires that models of allostatic load display properties of measurement invariance across age groups. Because most research on allostatic load has featured older adults, it is unclear if these requirements can be met. METHODS: To address this question, we fit a series of exploratory and confirmatory analytic models to data on eight biomarkers using a nationally representative sample of N = 4260 children, adolescents, and young adults drawn from the National Health and Nutrition Examination Survey dataset. RESULTS: Exploratory and confirmatory models indicated that, consistent with allostatic load theory, a unidimensional model was a good fit to the data. However, this model did not display properties of measurement invariance; post-hoc analyses suggested that the biomarkers included in the final confirmatory model were most strongly intercorrelated among young adults and most weakly intercorrelated among adolescents. CONCLUSIONS: These results underscore the importance of testing assumptions about measurement invariance in allostatic load before drawing substantive conclusions about stress, disadvantage, and health by directly comparing levels of allostatic load across different stages of development, while underscoring the need to expand investigations of measurement invariance to samples of longitudinal data.

I like therefore I can, and I can therefore I like: the role of self-efficacy and affect in active inference of allostasis.

Active inference (AIF) is a theory of the behavior of information-processing open dynamic systems. It describes them as generative models (GM) generating inferences on the causes of sensory input they receive from their environment. Based on these inferences, GMs generate predictions about sensory input. The discrepancy between a prediction and the actual input results in prediction error. GMs then execute action policies predicted to minimize the prediction error. The free-energy principle provides a rationale for AIF by stipulating that information-processing open systems must constantly minimize their free energy (through suppressing the cumulative prediction error) to avoid decay. The theory of homeostasis and allostasis has a similar logic. Homeostatic set points are expectations of living organisms. Discrepancies between set points and actual states generate stress. For optimal functioning, organisms avoid stress by preserving homeostasis. Theories of AIF and homeostasis have recently converged, with AIF providing a formal account for homeo- and allostasis. In this paper, we present bacterial chemotaxis as molecular AIF, where mutual constraints by extero- and interoception play an essential role in controlling bacterial behavior supporting homeostasis. Extending this insight to the brain, we propose a conceptual model of the brain homeostatic GM, in which we suggest partition of the brain GM into cognitive and physiological homeostatic GMs. We outline their mutual regulation as well as their integration based on the free-energy principle. From this analysis, affect and self-efficacy emerge as the main regulators of the cognitive homeostatic GM. We suggest fatigue and depression as target neurocognitive phenomena for studying the neural mechanisms of such regulation.

Biomarker Profiles of Depression During Young Adulthood: Results From the National Health and Nutrition Examination Survey.

PURPOSE: Cumulative "wear and tear" on physiological systems (allostatic load) may contribute to risk for depression, but there is limited research on allostatic load during young adulthood, which is a peak developmental period for depression onset. This study evaluates profiles of allostatic load and their association with depression in young adults. METHODS: Biomarker and depression data were extracted for 18-24-year-olds (928 females, 932 males) in the National Health and Nutrition Examination Survey from 2015 to 2020. Latent class analysis was used to identify biomarker profiles. Multivariate logistic regression analyses were used to predict depression based on profile membership, controlling for sociodemographic characteristics. RESULTS: Three allostatic load profiles were identified in both females and males-high inflammatory and moderate metabolic dysregulation (immunometabolic dysregulation), high metabolic and moderate inflammatory dysregulation (metaboimmune dysregulation), or low dysregulation. Metaboimmune or immunometabolic dysregulation profiles in females, and metaboimmune dysregulation in males, were associated with 3-3.5 times greater odds of depression compared to low dysregulation profiles. DISCUSSION: Profiles of immune and metabolic dysregulation can be observed during young adulthood. Elevated immunometabolic and metaboimmune profiles were associated with depression risk in young adult females, while elevated metaboimmune profiles were associated with depression risk in young adult males. Detection of depression-related physiological dysregulation in young adults could be used to identify depression phenotypes and apply early interventions.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

OBJECTIVES: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark. DESIGN: Register-based study. SETTING: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study. Nine biomarkers (systolic blood pressure, diastolic blood pressure, pulse rate, total serum cholesterol, high-density lipoprotein cholesterol, waist-to-hip ratio, triglycerides, C-reactive protein and serum albumin) were divided into high-risk and low-risk values based on clinically accepted criteria, and the AL index was defined as the average between the nine values. All-cause mortality data were obtained from Statistics Denmark. PARTICIPANTS: We examined a total of 106 808 individuals aged 40-79 years. PRIMARY OUTCOME MEASURE: Linear regression models were performed to investigate the association between mean AL index and cumulative mortality risk. RESULTS: Mean AL index was higher in men (range 2.3-3.3) than in women (range 1.7-2.6). We found AL index to be strongly correlated with the cumulative mortality rate, correlation coefficient of 0.82. A unit increase in mean AL index corresponded to an increase in the cumulative mortality rate of 19% (95% CI 13% to 25%) for men, and 16% (95% CI 8% to 23%) for women but this difference was not statistically significant. The overall mean increase in cumulative mortality rate for both men and women was 17% (95% CI 14% to 20%). CONCLUSIONS: Our findings indicate the population-based AL index to be a strong indicator of community health, and suggest identification of targets for reducing AL.

Allostatic load and chronic pain: a prospective finding from the national survey of midlife development in the United States, 2004-2014.

BACKGROUND: Previous research has demonstrated a correlation between chronic stress and chronic pain (CP). However, there have been few studies examining the prospective association of allostatic load (AL)-the biological processes related to stress-with CP. METHODS: We firstly conducted latent class analysis to identify phenotypes of AL using a community-dwelling sample, the Midlife in the United States. Multinomial logistic regression models were used to examine the prospective association between phenotypes of AL at MIDUS 2 biomarker project and the presence of CP, CP interference and the number of CP sites at MIDUS 3. RESULTS: Three phenotypes of AL, low biological dysregulation, parasympathetic dysregulation and metabolic dysregulation, were identified. Compared to low biological dysregulation group, participants experiencing metabolic dysregulation phenotype of AL at MIDUS 2 had higher risks of having high-interference CP (RRR = 2.00, 95% CI: 1.06, 3.79, P < 0.05) and 3 or more CP sites (RRR = 2.03, 95% CI: 1.08, 3.83, P < 0.05) at MIDUS 3. CONCLUSION: The findings indicate that focusing on mitigating the metabolic dysfunction phenotype of AL has the potential to be an efficacious strategy for alleviating future CP bodily widespreadness and high CP interference.

Berry Consumption in Relation to Allostatic Load in US Adults: The National Health and Nutrition Examination Survey, 2003-2010.

INTRODUCTION: Berries are a rich source of antioxidant polyphenols and other nutrients that are associated with good health. Allostatic load (AL) is an aggregate measure of chronic stress-induced physiological dysregulations across cardiovascular, metabolic, autonomic, and immune systems; the extent of these dysregulations, collectively or in each system, can be characterized by a composite score or a domain score assessed by integrated biomarkers. It was hypothesized that the anti-inflammatory and other effects of berries lower AL. The association was determined between berry consumption and AL composite and domain scores in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). METHODS: Berry intake was measured using two 24 h dietary recalls collected from US adults in the 2003-2010 NHANES (n = 7684). The association with AL and its specific domains was examined using population weight-adjusted multivariable linear regression. RESULTS: The mean AL composite scores for consumers of any berries (11.9), strawberries (11.6), and blueberries (11.6), respectively, were significantly lower than nonconsumers (12.3), after fully adjusting for sociodemographic, lifestyle, and dietary confounders. A significant dose-response relationship was determined between greater consumption of total berries, strawberries, and blueberries and lower mean AL composite scores (p-trend < 0.05, for all). Consistently, mean cardiovascular and metabolic domain scores remained significantly lower in the consumers of total berries (mean cardiovascular domain score: 4.73 versus 4.97 for nonconsumers; mean metabolic domain score: 2.97 versus 3.1), strawberries (4.73 versus 4.95; 2.99 versus 3.1), and blueberries (4.6 versus 4.95; 2.92 versus 3.11). Berry consumers also had significantly lower mean AL immune scores (1.52 versus 1.56) and lower mean AL autonomic scores (2.49 versus 2.57) than nonconsumers (initial sample: n = 15,620). CONCLUSIONS: The current study indicates that consumption of berries lowers the AL composite scores and potentially reduces stress-related disease risks in the US adult population.

Stress, Allostatic Load, and Neuroinflammation: Implications for Racial and Socioeconomic Health Disparities in Glaucoma.

Glaucoma is the leading cause of irreversible blindness, and its pathophysiology includes neuroinflammatory changes. The present therapies for glaucoma target pressure-lowering mechanisms with limited success, making neuroinflammation a target for future interventions. This review summarizes the neuroinflammatory pathways seen in glaucoma and their interplay with stress. Glucocorticoids have been shown to activate proinflammatory glial cells, contributing to the neuroinflammation in glaucoma. Glucocorticoids have also been shown to increase the IOP directly. Stress-associated autonomic dysfunction can affect the vascular homeostasis in the retina and create oxidative stress. Diabetes, hyperglycemic-mediated endothelial damage, and vascular inflammation also play important roles in the neuroinflammation in glaucoma and diabetic retinopathy. Psychosocial stress has been implicated in an increased IOP and glaucoma outcomes. People who experience maladaptive chronic stress suffer from a condition known as allostatic load, which describes pathologic neuroendocrine dysregulation. The effects of allostatic load and chronic stress have been studied in patients affected by a lower socioeconomic status (SES) and marginalized racial identities. A lower SES is associated with higher rates of glaucoma and also affects the access to care and screening. Additionally, people of African ancestry are disproportionately affected by glaucoma for reasons that are multifactorial. In conclusion, this review explores neuroinflammation in glaucoma, highlighting opportunities for future investigation.

Correlation of allostatic load and perceived stress with clinical features in first-episode schizophrenia.

BACKGROUND: Stress plays an important role in the etiology of schizophrenia. However, the mechanisms by which chronic physiological stress and perceived stress relate to the clinical features of schizophrenia may differ. We aimed to elucidate the relationships among chronic physiological stress indexed by allostatic load (AL), perceived stress, and clinical symptoms in individuals with first-episode schizophrenia (FES). METHODS: Individuals with FES (n = 90, mean age = 28.26years old, 49%female) and healthy controls (111, 28.88, 51%) were recruited. We collected data of 13 biological indicators to calculate the AL index, assessed subjective stress with the Perceived Stress Scale-14 (PSS-14), and compared AL and perceived stress between groups. Patients with FES were also evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: Individuals with FES had higher AL and PSS score than healthy controls. There were no significant correlations between AL and PSS score in either patients or controls. Among individuals with FES, the AL index was associated with the severity of positive symptoms, while the PSS score was positively associated with CDSS score. Both elevated AL and PSS were correlated with the occurrence of schizophrenia. CONCLUSIONS: Physiological stress, as reflected by AL, may be more related to positive symptoms, while perceived stress appear to be associated with depressive symptoms in individuals with FES. Longitudinal studies are necessary to explore the relationships between interventions for different stressor types and specific clinical outcomes in FES.

The mediating role of child delay of gratification in the link between early and prolonged poverty exposure and adolescent allostatic load.

Early and prolonged exposure to poverty disrupts biological processes associated with the body's stress response system, leading to long-term negative health outcomes, including obesity, autoimmune disorders, and cardiovascular disease. Allostatic load (AL), a composite measure of chronic stress on the body, is a robust predictor of subsequent health outcomes. However, developmental research examining the associations of early poverty exposure with AL in adolescence, as well as the underlying mechanisms of influence is limited. Early poverty exposure also impedes healthy development of child self-regulation, which may increase risk for high AL in adolescence, but this mechanistic pathway has not yet been tested. We used data from the national Study of Early Child Care and Youth Development (SECCYD) to examine the longitudinal associations between prolonged poverty exposure in early childhood (0-3 years) and AL in adolescence (age 15). We also tested the mediating role of child delay of gratification, a behavioral measure of self-regulation (at age 54 months), in the potential association between early poverty exposure and adolescent AL. Accounting for model covariates (i.e., child biological sex and race-ethnicity) and individual differences in child delay of gratification, early and prolonged poverty exposure was significantly associated with higher AL at age 15. The indirect effect through child delay of gratification was not significant, but the individual pathways of the indirect effect were significant, and the overall direct association of early poverty exposure with adolescent AL was significant. Our findings show that prolonged exposure to poverty in early childhood (0-3 years) can have significant negative associations with both child delay of gratification (at 54 months) and AL (at age 15). Given that the detrimental impacts of poverty exposure can be detected at an early age, targeted prevention efforts (e.g., anti-poverty programs such as cash assistance programs) may be able to offset some of the risks of early poverty exposure on self-regulation and AL.

Migraine as an allostatic reset triggered by unresolved interoceptive prediction errors.

Until now, a satisfying account of the cause and purpose of migraine has remained elusive. We explain migraine within the frameworks of allostasis (the situationally-flexible, forward-looking equivalent of homeostasis) and active inference (interacting with the environment via internally-generated predictions). Due to its multimodality, and long timescales between cause and effect, allostasis is inherently prone to catastrophic error, which might be impossible to correct once fully manifest, an early indicator which is elevated prediction error (discrepancy between prediction and sensory input) associated with internal sensations (interoception). Errors can usually be resolved in a targeted manner by action (correcting the physiological state) or perception (updating predictions in light of sensory input); persistent errors are amplified broadly and multimodally, to prioritise their resolution (the migraine premonitory phase); finally, if still unresolved, progressive amplification renders further changes to internal or external sensory inputs intolerably intense, enforcing physiological stability, and facilitating accurate allostatic prediction updating. As such, migraine is an effective 'failsafe' for allostasis, however it has potential to become excessively triggered, therefore maladaptive.

Educational patterning in biological health seven years apart: Findings from the Tromsø Study.

BACKGROUND: Social-to-biological processes is one set of mechanisms underlying the relationship between social position and health. However, very few studies have focused on the relationship between social factors and biology at multiple time points. This work investigates the relationship between education and the dynamic changes in a composite Biological Health Score (BHS) using two time points seven years apart in a Norwegian adult population. METHODS: We used data from individuals aged 30 years and above who participated in Tromsø6 (2007-2008) and Tromsø7 (2015-2016) (n = 8117). BHS was defined using ten biomarkers measured from blood samples and representing three physiological systems (cardiovascular, metabolic, inflammatory). The higher the BHS, the poorer the health status. FINDINGS: Linear regression models carried out on BHS revealed a strong educational gradient at two distinct time points but also over time. People with lower educational attainment were at higher risk of poor biological health at a given time point (ßlow education Tromsø6=0.30 [95 %-CI=0.18-0.43] and ßlow education Tromsø7=0.30 [95 %-CI=0.17-0.42]). They also presented higher longitudinal BHS compared to people with higher education (ßlow education = 0.89 [95 %-CI=0.56-1.23]). Certain biomarkers related to the cardiovascular system and the metabolic system were strongly socially distributed, even after adjustment for sex, age, health behaviours and body mass index. CONCLUSION: This longitudinal analysis highlights that participants with lower education had their biological health deteriorated to a greater extent over time compared to people with higher education. Our findings provide added evidence of the biological embodiment of social position, particularly with respect to dynamic aspects for which little evidence exists.

Allostatic load and risk of invasive breast cancer among postmenopausal women in the U.S.

OBJECTIVE: Allostatic load can reflect the body's response to chronic stress. However, little is known about the association between allostatic load and risk of breast cancer in postmenopausal women. This study used a large prospective cohort in the United States to examine the relationship between allostatic load and invasive breast cancer risk, and to evaluate the relationship by racial and ethnic identity and breast cancer subtypes. METHODS: Among 161,808 postmenopausal participants in Women's Health Initiative, eligible were a subsample of 27,393 postmenopausal women aged 50-79 years old, who enrolled from 1993 to 1998, had serum test biomarkers, and were followed for breast cancer incidence through February 2022. Allostatic load at enrollment was computed based on eight biomarkers from lab serum tests and a questionnaire about participants' prescription drug use. The associations between allostatic scores and risk of breast cancer (overall and by subtypes) were assessed using Cox proportional hazards models. The race and ethnic differences were examined. RESULTS: Over a median follow-up time of 17.24 years, 1722 invasive breast cancer cases were identified. High allostatic load was associated with an increased risk of breast cancer (HR = 1.36, 95%CI: 1.20, 1.54 for third tertile vs first tertile, Ptrend < 0.0001). Similar trends were found in White women and non-Hispanic women. Higher allostatic load was associated with hormone receptor-positive and HER2/Neu-negative breast cancer (HR = 1.54, 95%CI: 1.30, 1.80 for third tertile vs first tertile, Ptrend < 0.0001). CONCLUSION: In this study, we found that higher allostatic load was significantly associated with an increased risk of breast cancer in postmenopausal women.

The interrelationships of hearing function, allostatic load, and cognitive function: Evidence among middle-aged and older Chinese adults.

OBJECTIVES: We aim to examine the interrelationships of self-reported hearing function, allostatic load (AL), and cognitive function among middle aged and older adults. METHODS: Our data were collected from two waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 and 2015. The participants' hearing function was measured using self-rated subjective hearing function. Allostatic load (AL) was evaluated by measuring 14 biomarkers associated with physiological health, which were derived from blood samples. Cognitive function was assessed using three domains: episodic memory, mental intactness, and global cognition. To examine the relationships between hearing function, AL, and cognitive function, path analysis with structural equation modeling (SEM) methodology was employed. RESULTS: Among individuals aged 60 and above non-hearing aids users, the hearing function at Time 1 (T1) in 2011 has a significant association with the level of AL at T1 (ß = 0.02, p < 0.001), as well as on cognitive function at Time 2 (T2) in 2015 (ß = -0.1, p < 0.001). Additionally, the AL related to the hearing function at T1 associates an increased risk of AL at T2 (ß = 0.5, p < 0.001), and is significantly associated with a decrease of cognitive function scores at T2 (ß = -0.4, p < 0.001). However, no significant relationship was found among individuals aged 45 - 59 with non-hearing aids utilizers. Similar findings were in the domains of epidemic memory and mental intactness for cognitive function. CONCLUSIONS: There were interrelationships of subjective hearing function, AL, and cognitive function among aged 60 years and above, but not among those aged 45-59 years old. It may provide valuable insights for identifying subclinical thresholds in the physiological systems of individuals at risk of pathology in cognitive function.

Conceptual foundations of physiological regulation incorporating the free energy principle and self-organized criticality.

Bettinger, J. S., K. J. Friston. Conceptual Foundations of Physiological Regulation incorporating the Free Energy Principle & Self-Organized Criticality. NEUROSCI BIOBEHAV REV 23(x) 144-XXX, 2022. Since the late nineteen-nineties, the concept of homeostasis has been contextualized within a broader class of "allostatic" dynamics characterized by a wider-berth of causal factors including social, psychological and environmental entailments; the fundamental nature of integrated brain-body dynamics; plus the role of anticipatory, top-down constraints supplied by intrinsic regulatory models. Many of these evidentiary factors are integral in original descriptions of homeostasis; subsequently integrated; and/or cite more-general operating principles of self-organization. As a result, the concept of allostasis may be generalized to a larger category of variational systems in biology, engineering and physics in terms of advances in complex systems, statistical mechanics and dynamics involving heterogenous (hierarchical/heterarchical, modular) systems like brain-networks and the internal milieu. This paper offers a three-part treatment. 1) interpret "allostasis" to emphasize a variational and relational foundation of physiological stability; 2) adapt the role of allostasis as "stability through change" to include a "return to stability" and 3) reframe the model of homeostasis with a conceptual model of criticality that licenses the upgrade to variational dynamics.

[Allostasis and Homeostasis: Dynamic Adaptive Systems from a Neurophysiological Perspective].

Homeostasis is a well-known physiological principle that refers to a stable internal environment. Allostasis, on the other hand, is a more recently understood physiological principle based on predictive control, in which the setpoint of the internal environment is dynamically adjusted to increase control efficiency. The concept of allostasis continues to evolve with advances in the field of neuroscience. This overview introduces some new findings and broadens the concept of allostasis to apply it to the inter-regulation of the cognitive, somatic, and autonomic nervous systems. This article will describe on way in which biological systems alter themselves to adapt to their external and internal environments.

[Allostasis and Resilience from a Neuroendocrine Perspective].

Resilience is a term that describes the capacity of coping with and recovering from stress and adversity. In terms of the concept of allostasis, resilience is the ability to appropriately regulate allostasis, efficiently terminate the allostatic response, prevent the occurrence of allostatic load/overload or restore homeostasis. Recently, it has been shown that oxytocin may be involved in this series of stress adaptation systems. We aim to discuss the changes in oxytocin neuron activation, oxytocin release and its actions of stress adaptation in response to internal and external environmental changes, and the regulation of resilience by oxytocin.

[Detection and Application of Allostatic Load through Internet of Things Measurements].

Allostatic load refers to a vulnerable state of the nervous system caused by chronic or repeated exposure to challenges of daily life (e.g., psychological stressors) and considered to indicate risk of a transition to pathological state. In this paper, we first introduce a traditional method of assessing allostatic load that utilizes multiple biomarkers. Next, we demonstrate the potential of the Internet of Things (IoT) data sampling method to detect and control the vulnerable state in daily life.

[Allostasis and Heart Rate Variability Analysis].

This paper reviews patterns of heart rate variability and mechanisms of allostasis. The paper focuses on traditional autonomic nervous system and brain-heart axis research, recent biological measurements, and ambulatory electrocardiogram (ECG) big data analysis. The importance of biological measurement of daily activities and the results of data-driven research that analyzes ECG big data will provide new insights into the use of bio-signals.

[The Design Principle of Allostatic Mechanisms: The Free Energy Principle].

Homeostasis is maintained by neural reflex controls, which attempt to maintain the body's internal organs within a predetermined range. However, when deviations are significant, homeostasis may not be restored by these standard controls. Therefore, a function called allostasis is necessary to maximize the energy efficiency of bodily functions, anticipate changing needs (e.g., a future increase in body temperature or oxygen demand), and regulate the body's state before dyshomeostasis occurs. In terms of the free energy principle (FEP), the expectation to survive (i.e., to stay within established confines and to maintain homeostatic integrity over time) is realized by a hierarchical prediction mechanism. Allostasis requires the integration of exteroceptive, interoceptive, and proprioceptive signals. In this paper, the neural mechanism of allostasis is discussed in terms of the FEP.