Biomarkers Of Resilience Research Articles

Functional neuroimaging biomarkers of resilience in major depressive disorder.

In this review we provide an overview of definitions and determinants of resilience in the context of neuroimaging research in major depressive disorder (MDD). We summarize emerging literature on functional neuroimaging biomarkers of resilience in MDD and discuss their clinical relevance and implications for future research. Resilience in MDD is characterized by dissociable profiles of activation and functional connectivity within brain networks involved in cognitive control, emotion regulation, and reward processing. Increased activation of frontal cortical brain regions implicated in cognitive appraisal and emotion regulation is a common characteristic of resilient individuals at high risk for MDD and of individuals with MDD with a favorable illness course. Furthermore, significant associations between fronto-striato-limbic functional connectivity and both positively interpreted stressful life events in resilient high-risk individuals and a favorable response to first-line treatments in depressed individuals suggest that neuro-compensatory changes and experience-dependent plasticity underlie resilience in MDD. Emerging research has identified functional neuroimaging biomarkers of resilience in MDD. A continued focus on identifying neurobiological underpinnings of resilience, in the context of dynamic environmental and developmental influences, will advance our understanding of resilience and improve approaches to prevention and treatment of MDD.

Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation

The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression. This model generates two stress-response phenotypes: CSIS-sensitive (depressive-like behaviour) and CSIS-resilience assessed by means of sucrose preference and forced swim tests. Our aim was to characterize the synaptoproteome changes representative of potential long-term changes in protein expression underlying susceptibility or resilience to stress. Proteomic data showed increased expression of glycolytic enzymes, the energy-related mitochondrial proteins, actin cytoskeleton, signalling transduction and synaptic transmission proteins in CSIS-sensitive rats. Protein levels of glutamate-related enzymes such as glutamate dehydrogenase and glutamine synthetase were also increased. CSIS-resilient rats showed similar proteome changes, however with a weaker increase compared to CSIS-sensitive rats. The main difference was observed in the level of protein expression of vesicle-mediated transport proteins. Nonetheless, only few proteins were uniquely up-regulated in the CSIS-resilient rats, whereby Cytochrome b-c1 complex subunit 2, mitochondrial (Uqcrc2) and Voltage-dependent anion-selective channel protein 1 (Vdac1) were uniquely down-regulated. Identified altered activated pathways and potential protein biomarkers may help us better understand the molecular mechanisms underlying synaptic neurotransmission in MD or resilience, crucial for development of new therapeutics.

The prediction of resilience to alcohol consumption in youths: insular and subcallosal cingulate myeloarchitecture.

The prediction of alcohol consumption in youths and particularly biomarkers of resilience, is critical for early intervention to reduce the risk of subsequent harmful alcohol use. At baseline, the longitudinal relaxation rate (R1), indexing grey matter myelination (i.e. myeloarchitecture), was assessed in 86 adolescents/young adults (mean age = 21.76, range: 15.75-26.67 years). The Alcohol Use Disorder Identification Test (AUDIT) was assessed at baseline, 1- and 2-year follow-ups (12- and 24-months post-baseline). We used a whole brain data-driven approach controlled for age, gender, impulsivity and other substance and behavioural addiction measures, such as problematic cannabis use, drug use-related problems, internet gaming, pornography use, binge eating, and levels of externalization, to predict the change in AUDIT scores from R1. Greater baseline bilateral anterior insular and subcallosal cingulate R1 (cluster-corrected family-wise error p < 0.05) predict a lower risk for harmful alcohol use (measured as a reduction in AUDIT scores) at 2-year follow-up. Control analyses show that other grey matter measures (local volume or fractional anisotropy) did not reveal such an association. An atlas-based machine learning approach further confirms the findings. The insula is critically involved in predictive coding of autonomic function relevant to subjective alcohol cue/craving states and risky decision-making processes. The subcallosal cingulate is an essential node underlying emotion regulation and involved in negative emotionality addiction theories. Our findings highlight insular and cingulate myeloarchitecture as a potential protective biomarker that predicts resilience to alcohol misuse in youths, providing novel identifiers for early intervention.

Psychological resilience is correlated with dynamic changes in functional connectivity within the default mode network during a cognitive task

Resilience is a dynamic process that enables organisms to cope with demanding environments. Resting-state functional MRI (fMRI) studies have demonstrated a negative correlation between resilience and functional connectivities (FCs) within the default mode network (DMN). Considering the on-demand recruitment process of resilience, dynamic changes in FCs during cognitive load increases may reflect essential aspects of resilience. We compared DMN FC changes in resting and task states and their association with resilience. Eighty-nine healthy volunteers completed the Connor–Davidson Resilience Scale (CD-RISC) and an fMRI with an auditory oddball task. The fMRI time series was divided into resting and task periods. We focused on FC changes between the latter half of the resting period and the former half of the task phase (switching), and between the former and latter half of the task phase (sustaining). FCs within the ventral DMN significantly increased during “switching” and decreased during “sustaining”. For FCs between the retrosplenial/posterior cingulate and the parahippocampal cortex, increased FC during switching was negatively correlated with CD-RISC scores. In individuals with higher resilience, ventral DMN connectivities were more stable and homeostatic in the face of cognitive demand. The dynamic profile of DMN FCs may represent a novel biomarker of resilience.

Kinetics of Physiological Responses as a Measure of Intensity and Hydration Status During Experimental Physical Stress in Human Volunteers

IntroductionStrenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers.AimTo analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol.MethodsAfter determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction.ResultsKinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax.ConclusionHigh (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.

Effects of Hemp Extract on Markers of Wellness, Stress Resilience, Recovery and Clinical Biomarkers of Safety in Overweight, But Otherwise Healthy Subjects

We determined the effects of a commercially available, GRAS (Generally Recognized As Safe) by independent conclusion, CBD-containing hemp oil extract on stress resilience, perceived recovery, mood, affect, body composition, and clinical safety markers in healthy human subjects.Methods: Using a randomized, placebo-controlled, double-blind design, 65 overweight, but otherwise healthy men and women (35.2 ± 11.4 years, 28.5 ± 3.3 kg/m2) ingested either Hemp Oil Extract [Hemp, 60 mg/d PlusCBDTM Extra Strength Hemp Extract Oil (15 mg hemp-derived CBD)] or a placebo (PLA) every day for six weeks while continuing to follow their normal diet and physical activity patterns. Outcome variables included changes in stress resilience, a 14-item panel of various psychometric parameters, heart-rate variability, plasma chromogranin A, body composition, and general markers of health. Data were analyzed using mixed factorial ANOVA, t-tests with 95% confidence intervals, and effect sizes (ES).Results: HDL cholesterol significantly improved in the Hemp group (p = 0.004; ES = 0.75). No other statistically significant group x time interaction effects were observed. Statistical tendencies for between-group differences were found for ‘I Get Pleasure From Life’ (p = 0.06, ES = 0.48) and ‘Ability to Cope with Stress’ (p = 0.07, ES = 0.46). Sleep quality (Hemp, p = 0.005, ES = 0.54) and sleep quantity (Hemp, p = 0.01, ES = 0.58) exhibited significant within-group changes. All values for hepato-renal function, cardiovascular health, fasting blood lipids, and whole blood cell counts remained within normal clinical limits with no between-group differences over time being identified.Conclusions: Hemp supplementation improved HDL cholesterol, tended to support psychometric measures of perceived sleep, stress response, and perceived life pleasure and was well tolerated with no clinically relevant safety concerns. Registered at clinicaltrials.gov: NCT04294706.

Chen A, ed. Stress Resilience: Molecular and Behavioral Aspects. London, England: Academic Press; 2020.

Chen A, ed. Stress Resilience: Molecular and Behavioral Aspects. London, England: Academic Press; 2020.

Biomarkers Associated with Physical Resilience After Hip Fracture.

Clinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable to differences in physical resilience. However, molecular mechanisms underlying physical resilience are unknown. We previously derived a measure of physical resilience after hip fracture-the expected recovery differential (ERD)-that captures the difference between actual recovery and predicted recovery. Starting with biomarkers associated with physical performance, morbidity, mortality, and hip fracture, we evaluated associations with the ERD to identify biomarkers of physical resilience after hip fracture. In the Baltimore Hip Studies (N = 304) sera, we quantified biomarkers of inflammation (TNFR-I, TNFR-II, sVCAM-1, and IL-6), metabolic and mitochondrial function (non-esterified fatty acids, lactate, ketones, acylcarnitines, free amino acids, and IGF-1), and epigenetic dysregulation (circulating microRNAs). We used principal component analysis, canonical correlation, and least absolute shrinkage and selection operator regression (LASSO) to identify biomarker associations with better-than-expected recovery (greater ERD) after hip fracture. Participants with greater ERD were more likely to be women and less disabled at baseline. The complete biomarker set explained 37% of the variance in ERD (p < .001) by canonical correlation. LASSO regression identified a biomarker subset that accounted for 27% of the total variance in the ERD and included a metabolic factor (aspartate/asparagine, C22, C5:1, lactate, glutamate/mine), TNFR-I, miR-376a-3p, and miR-16-5p. We identified a set of biomarkers that explained 27% of the variance in ERD-a measure of physical resilience after hip fracture. These ERD-associated biomarkers may be useful in predicting physical resilience in older adults facing hip fracture and other acute health stressors.

Family Dynamics and Emotion Processing: Functional Connectivity Biomarkers of Risk and Resilience in Youth at Familial Risk for Mood Disorders

We have limited understanding of the neural mechanisms that underlie resilience (RES) versus conversion to psychopathology (CVT) in youth at familial risk for mood disorders (FR). Family function may be a key environmental influence on emotion regulation and clinical symptoms in youth, particularly in those at FR.

RESEARCH AWARD SESSION: RESILIENCE AND LATE-LIFE DEPRESSION: CLINICAL FEATURES; BIOMARKERS; AND INTERVENTIONS

Psychological resilience has been broadly defined as “the capacity to maintain, or regain, psychological well-being in the face of challenge” Resilience is a complex construct that can be conceptualized as an attribute (a trait) that is possessed to varying degrees by different individuals, a dynamic process (a state) with bidirectional relations to developmental and environmental factors, and as an outcome in the face of stress and adversity. Few studies have investigated resilience in depression, and even fewer have examined resilience in depressed older adults and as a target for novel interventions to treat depression. In this presentation, clinical features of resilience relevant for depression outcomes will be discussed. The biomarkers of resilience will be presented. Approaches to using mind-body and antidepressant interventions boosting psychological and cognitive resilience will be highlighted.

Potential chemokine biomarkers associated with PTSD onset, risk and resilience as well as stress responses in US military service members

Cytokines, including chemokines, are small secreted proteins, which specifically effect on the interactions and communications between cells. Pro-inflammatory cytokines are produced predominantly by activated macrophages and are involved in the upregulation of inflammatory reactions. Dysregulation of cytokines is associated with post-traumatic stress disorder (PTSD). Here, we use both before-and-after and case–control studies to search for potential chemokine biomarkers associated with PTSD onset, risk, and resilience as well as stress responses in US military service members deployed to Iraq and Afghanistan. Blood samples and scores of the PTSD Checklist (PCL) were obtained from soldiers pre- and post deployment (pre, post). Forty chemokines were measured using the Bio-Plex Pro Human Chemokine Panel Assays. The before-and-after analysis showed potential markers (CCL2, CCL15, CCL22, CCL25, CXCL2, and CXCL12) are associated with PTSD onset, and CCL3, CXCL11, and CXCL16 are related to stress response. The case–control study demonstrated that CCL13, CCL20, and CXCL6 were possible PTSD risk markers, and CX3CL1 might be a resilience marker. In addition, CCL11, CCL13, CCL20, and CCL25 were correlated with the PCL scores, indicating their association with PTSD symptom severity. Our data, for the first time, suggest that these dysregulated chemokines may serve as biomarkers for PTSD onset, risk, and resilience as well as stress responses, and may benefit developing approaches not only for PTSD diagnosis but also for PTSD treatment.

Hair cortisol as a biomarker of stress and resilience in South African mixed ancestry females

BackgroundHair cortisol concentrations (HCC) are increasingly used as a biomarker of stress, however limited research exists regarding the relationship between HCC and protective factors, such as resilience. Additionally, studies measuring HCC need to account for possible confounders, and these factors have not been examined in sufficiently diverse settings. ObjectivesOur objectives were to identify determinants of HCC in a sample of mixed ancestry adults and investigate the association of HCC with measures of self-perceived stress and resilience. MethodsOur sample comprised 164 females (mean age 46.5 years, SD = 15.0), self-identifying as mixed ancestry, who were control participants in a case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined which socio-demographic, hair related, clinical and behavioural factors were associated with HCC in both unadjusted and adjusted linear regression models. Furthermore, the relationship of HCC with self-perceived stress and resilience scores were also examined. ResultsHCC (Mdn 4.4 pg/ml; IQR 2.8; 11.4) were significantly positively associated with hair product use and breastfeeding, and significantly negatively associated with age, level of education, duration of sun exposure, duration of storage, and demonstrated a trend towards significance with frequency of hair washing, in adjusted models. HCC were inversely associated with CD-RISC scores (adj β = −0.179, p = 0.012) but were not significantly associated with PSS scores (adj β = −0.001, p = 0.989). ConclusionsWe identified specific determinants of HCC in our sample, including the first indication that sun exposure has an effect on HCC under naturalistic conditions. These potential confounders need to be controlled for in the design and analysis of future studies. HCC may be a biomarker of resilience to stress, rather than perceived stress. Further research measuring HCC in more diverse settings and populations and including constructs related to resilience are needed.

Predicting stress resilience and vulnerability: brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses.

To examine the rapid eye movement sleep (REM) response to mild stress as a predictor of the REM response to intense stress and brain-derived neurotrophic factor (BDNF) as a potential biomarker of stress resilience and vulnerability. Outbred Wistar rats were surgically implanted with electrodes for recording electroencephalography (EEG) and electromyogram (EMG) and intraperitoneal Data loggers to record body temperature. Blood was also obtained to measure circulating BDNF. After recovery, rats were exposed to mild stress (novel chamber, NC) and later intense stress (shock training, ST), followed by sleep recording. Subsequently, rats were separated into resilient (Res; n=27) or vulnerable (Vul; n = 15) based on whether or not there was a 50% or greater decrease in REM after ST compared to baseline. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of mild and intense stress to determine if BDNF was predictive of the REM response. REM totals in the first 4 hours of sleep after exposure to NC predicted REM responses following ST with resilient animals having higher REM and vulnerable animals having lower REM. Resilient rats had significantly higher baseline peripheral BDNF compared to vulnerable rats. These results show that outbred rats display significant differences in post-stress sleep and peripheral BDNF identifying these factors as potential markers of resilience and vulnerability prior to traumatic stress.

Rerouting Geriatric Medicine by Complementing Static Frailty Measures With Dynamic Resilience Indicators of Recovery Potential.

Medicine is still very inadequate in forecasting recovery of tipping points in health and disease, especially in older adults. However, increasingly, diseases and invasive treatments unexpectedly push older patients with low resilience over their tipping points (TPs). These TPs are the points in human physiology that separate more healthy conditions from disease conditions or malfunctioning of the older human’s subsystems or organs, such as delirium, syncope and falls in old age, which threaten the functioning of the older person as a whole. Either the person may recover from the perturbation induced by such a subsystem TP and the balance of the whole system is restored, or the TP may set in motion a cascade of events driving the system down to a state of more decline, ultimately leading to death. A main unanswered question here is how to predict whether these older persons will recover or not. To improve this TP-recovery-forecasting, intriguing findings on measures of resilience found in other complex biological systems may be translated to humans. New dynamic resilience biomarkers for resilience can enrich clinical prediction for pathophysiological recovery and could test interventions for their effectiveness in improving resilience. Therefore, we hypothesize that dynamic, stimulus-response measures of recovery rate over time, observed after having received a minor stressor in a healthy condition, can be used to quantify recovery potential following subsystem TPs in disease and following invasive treatments in humans and thus the person’s resilience. Current static frailty prognostics can predict risks for death, institutionalization, delirium, falls, and other TP transitions, but it has not been proven that they can predict recovery. Our hypothesis on dynamic indicators of recovery is logical and timely, as it can now be studied with sensor technology to create a fundamentally different approach of variables that may be validated to forecast recovery potential. By generating dynamic measures of systemic resilience over various organ systems, we may subsequently model resilience generically across many chronic diseases, affecting different organ systems. Next, quantifying systemic resilience may reroute scientific and clinical pathways by predicting and preventing irreversible tipping points and by improving recovery by older adults.

Reward-circuit biomarkers of risk and resilience in adolescent depression.

Dysfunctional reward processing is a core feature of major depressive disorder. While there is growing knowledge of reward processing in adolescent depression, researchers have ignored neural mechanisms of resilience to depression. Here, we examine neural correlates of reward processing that characterize resilience and risk in adolescents at risk for depression, facilitating the development of effective intervention approaches that strengthen resilience to psychopathology in at-risk youth. 50 adolescent females were followed through age 18: 32 at-risk adolescents who either did (remitted-depressed; n = 15) or did not (resilient; n = 17) experience a depressive episode, and 18 low-risk healthy controls. Participants completed clinical assessments at 18-month intervals and an fMRI reward-processing task in late adolescence. We conducted predictive modeling with a priori reward regions of interest (ROIs). At-risk resilient and remitted-depressed adolescents exhibited less striatal activation than did controls during anticipation of reward. Resilient adolescents exhibited greater activation than did remitted-depressed adolescents in the middle frontal gyrus during reward anticipation, and less activation in the superior frontal gyrus and cuneus during processing of reward outcome. Using predictive modeling, ventral anterior cingulate cortex and putamen activation during reward processing distinguished resilient from remitted-depressed adolescents with 83% accuracy. The relatively small sample size of only females and the fact that fMRI data were obtained at one time point in late adolescence are limitations. Distinct patterns of neural activation in reward circuitry appear to be markers of risk and resilience that may be targets for prevention and treatment approaches aimed at strengthening adaptive reward processing in at-risk adolescents.

Genome-wide differential DNA methylation in tropically adapted Creole cattle and their Iberian ancestors.

Enhancing climate resilience and sustainable production for animals in harsh environments are important goals for the livestock industry given the predicted impacts of climate change. Rapid adaptation to extreme climatic conditions has already been imposed on livestock species, including those exported after Columbus's arrival in the Americas. We compared the methylomes of two Creole cattle breeds living in tropical environments with their putative Spanish ancestors to understand the epigenetic mechanisms underlying rapid adaptation of a domestic species to a new and more physiologically challenging environment. Reduced representation bisulfite sequencing was used to assess differences in methylation in Creole and Spanish samples and revealed 334 differentially methylated regions using high stringency parameters (P-value <0.01, ≥4 CpGs within a distance of 200bp, mean methylation difference >25%) annotated to 263 unique features. Gene ontology analysis revealed candidate genes involved in tropical adaptation processes, including genes differentially hyper- or hypomethylated above 80% in Creole samples displaying biological functions related to immune response (IRF6, PTGDR, FAM19A5, PGLYRP1), nervous system (GBX2, NKX2-8, RPGR), energy management (BTD), heat resistance (CYB561) and skin and coat attributes (LGR6). Our results entail that major environmental changes imposed on Creole cattle have had an impact on their methylomes measurable today, which affects genes implicated in important pathways for adaptation. Although further work is needed, this first characterization of methylation patterns driven by profound environmental change provides a valuable pointer for the identification of biomarkers of resilience for improved cattle performance and welfare under predicted climatic change models.

Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health.

The development of effective biomarkers for detecting the magnitude of radiation exposure and resiliency of host response is crucial to identifying appropriate treatment strategies after radiation exposure. We hypothesized that the gastrointestinal resident bacteria would demonstrate predictable, dose-dependent changes after radiation exposure across two large animal models of acute radiation syndrome. Here, Göttingen minipigs (GMP) (n = 50) and rhesus macaques (n = 48) were exposed to five dose levels (resulting in mortality rates of 33-100% and 25-68.7%, respectively). Fecal samples taken prior to and after irradiation (day 0 for GMP; day 0, 3 and 14 for macaques) were used for 16S rRNA gene sequence amplicon high-throughput sequencing. Baseline gut microbiota profiles were dissimilar between GMP and macaques, however, radiation appeared to have similar effect at the phylum level, resulting in Bacteroidetes decrease and Firmicutes increase in both models. The abundance of the main Bacteroidetes genus ( Bacteroides for GMP, Prevotella for macaques) was profoundly decreased by irradiation. Intracellular symbionts [Elusimicrobia in GMP, Treponema (Spirochaetes) in macaques] consistently increased after irradiation, suggesting their use as potential biomarkers of intestinal injury, and potential negative effect on health. Prevotella, Lactobacillus, Clostridium XIVa, Oscillibacter and Elusimicrobium/ Treponema abundances were found to be very significantly correlated with radiation intensity. Furthermore, Prevotella, Enterorhabdus and Ruminococcus and Enterorhabdus maintenance was strongly associated with survival in GMP, while Prevotella, Oscillibacter and Treponema were strongly associated with survival and Streptococcus with death in macaques. Overall, we found that a wide range of gut bacterial genera known to be abundant in the human gut microbiota are excellent biomarkers of radiation intensity and resilience in animal models, and that detrimental effects can be monitored, and potentially prevented, by targeting selected genera.

IN SEARCH OF BIOMARKERS OF RESILIENCE: MEASURING DONOR-SPECIFIC RESPONSES TO STRESS IN CELL-BASED ASSAYS

Resilience at the cellular level can be viewed as cell’s ability to respond to stress. Responses to hazardous exposures in vitro could reveal promising biomarkers of cellular resilience. We used endothelial progenitor cells from different individuals to test variability of responses to various stressors, including ionizing radiation, oxidative stress and inhibition of angiogenesis. Depending on the stressor, individuals show different degrees of variability in cellular responses. The greatest inter-individual variability was observed in response to oxidative stress, which is implicated in aging. We earlier demonstrated individual variability in total-body response to oxidative stress: greater urinary F2-isoprostane levels, oxidative status markers, were associated with stronger resistance. The underlying mechanism for both cellular and total-body resistance to oxidative stress may involve mitochondrial metabolism, and specifically individual ability to utilize fat as fuel. Direct measurement of mitochondrial metabolism in endothelial progenitor cells will determine whether it underlies cellular resistance to oxidative stress.

Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress.

This manuscript reviews recent evidence supporting the utility of telomeres and mitochondrial DNA copy number (mtDNAcn) in detecting the biological impacts of adverse childhood experiences (ACEs) and outlines mechanisms that may mediate the connection between early stress and poor physical and mental health. Critical to interrupting the health sequelae of ACEs such as abuse, neglect, and neighborhood disorder, is the discovery of biomarkers of risk and resilience. The molecular markers of chronic stress exposure, telomere length and mtDNAcn, represent critical biological links between ACEs and poor health outcomes. We examine how telomeres and mtDNAcn may exacerbate health disparities and contribute to the intergenerational transmission of trauma. Finally, we explore how these molecular markers of early stress exposure may help define the role of resilience and develop effective interventions to moderate ACE health risk impact.

Active aging \u2013 resilience and external support as modifiers of the disablement outcome: AGNES cohort study protocol

BackgroundPopulation aging increases the need for knowledge on positive aspects of aging, and contributions of older people to their own wellbeing and that of others. We defined active aging as an individual’s striving for elements of wellbeing with activities as per their goals, abilities and opportunities. This study examines associations of health, health behaviors, health literacy and functional abilities, environmental and social support with active aging and wellbeing. We will develop and validate assessment methods for physical activity and physical resilience suitable for research on older people, and examine their associations with active aging and wellbeing. We will examine cohort effects on functional phenotypes underlying active aging and disability.MethodsFor this population-based study, we plan to recruit 1000 participants aged 75, 80 or 85 years living in central Finland, by drawing personal details from the population register. Participants are interviewed on active aging, wellbeing, disability, environmental and social support, mobility, health behavior and health literacy. Physical activity and heart rate are monitored for 7 days with wearable sensors. Functional tests include hearing, vision, muscle strength, reaction time, exercise tolerance, mobility, and cognitive performance. Clinical examination by a nurse and physician includes an electrocardiogram, tests of blood pressure, orthostatic regulation, arterial stiffness, and lung function, as well as a review of chronic and acute conditions and prescribed medications. C-reactive protein, small blood count, cholesterol and vitamin D are analyzed from blood samples. Associations of factors potentially underlying active aging and wellbeing will be studied using multivariate methods. Cohort effects will be studied by comparing test results of physical and cognitive functioning with results of a cohort examined in 1989–90.ConclusionsThe current study will renew research on positive gerontology through the novel approach to active aging and by suggesting new biomarkers of resilience and active aging. Therefore, high interdisciplinary impact is expected. This cross-sectional study will not provide knowledge on temporal order of events or causality, but an innovative cross-sectional dataset provides opportunities for emergence of novel creative hypotheses and theories.