Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life

Timing of poverty in childhood and adolescent health: Evidence from the US and UK

Childhood poverty is associated with poorer adolescent health and health behaviours, but the importance of the timing of poverty remains unclear. There may be critical or sensitive periods in early life or early adolescence, or poverty may have cumulative effects throughout childhood. Understanding when poverty is most important can support efficient timing of interventions to raise family income or buffer against the effects of low income, but answers may vary across social contexts. The US and the UK are a useful comparison with similar liberal approaches to cash transfers, but very different approaches to healthcare provision. Utilising data from large population studies in the US (n = 9408; born 1979–1996) and UK (n = 1204; born 1991–1997), this study employs a structured life course approach to compare competing hypotheses about the importance of the timing or pattern of childhood exposure to poverty in predicting adolescent health limitations, symptoms of psychiatric distress, and smoking at age 16 (age 15/16 in US). Household income histories identified experience of poverty (measured as <60% of the national median equivalised income for a given year) in early life (ages 0–5), mid-childhood (ages 6–10) and early adolescence (ages 11–15). The Bayesian Information Criterion (BIC) compared fit across models with variables representing different life course patterns of exposure to poverty. Adolescent distress was not associated with poverty in either country. In both countries, however, variables representing cumulative or persistent experiences of poverty exhibited optimal fit of all poverty exposure variables in predicting adolescent smoking and health limitations. There was also evidence of an early life sensitive period for smoking in the US. Poverty was more persistent in the US, but associations between poverty and outcomes were consistent across countries. Although poverty can have cumulative effects on health and behaviour, early interventions may offer the best long-term protection

Assessing the Sensitivity of Different Life Stages for Sexual Disruption in Roach (Rutilus rutilus) Exposed to Effluents from Wastewater Treatment Works

Surveys of U.K. rivers have shown a high incidence of sexual disruption in populations of wild roach (Rutilus rutilus) living downstream from wastewater treatment works (WwTW), and the degree of intersex (gonads containing both male and female structural characteristics) has been correlated with the concentration of effluent in those rivers. In this study, we investigated feminized responses to two estrogenic WwTWs in roach exposed for periods during life stages of germ cell division (early life and the postspawning period). Roach were exposed as embryos from fertilization up to 300 days posthatch (dph; to include the period of gonadal sex differentiation) or as postspawning adult males, and including fish that had received previous estrogen exposure, for either 60 or 120 days when the annual event of germ cell proliferation occurs. Both effluents induced vitellogenin synthesis in both life stages studied, and the magnitude of the vitellogenic responses paralleled the effluent content of steroid estrogens. Feminization of the reproductive ducts occurred in male fish in a concentration-dependent manner when the exposure occurred during early life, but we found no effects on the reproductive ducts in adult males. Depuration studies (maintenance of fish in clean water after exposure to WwTW effluent) confirmed that the feminization of the reproductive duct was permanent. We found no evidence of ovotestis development in fish that had no previous estrogen exposure for any of the treatments. In wild adult roach that had previously received exposure to estrogen and were intersex, the degree of intersex increased during the study period, but this was not related to the immediate effluent exposure, suggesting a previously determined programming of ovotestis formation

Training the Fetal Immune System Through Maternal Inflammation-A Layered Hygiene Hypothesis.

Over the last century, the alarming surge in allergy and autoimmune disease has led to the hypothesis that decreasing exposure to microbes, which has accompanied industrialization and modern life in the Western world, has fundamentally altered the immune response. In its current iteration, the "hygiene hypothesis" suggests that reduced microbial exposures during early life restricts the production and differentiation of immune cells suited for immune regulation. Although it is now well-appreciated that the increase in hypersensitivity disorders represents a "perfect storm" of many contributing factors, we argue here that two important considerations have rarely been explored. First, the window of microbial exposure that impacts immune development is not limited to early childhood, but likely extends into the womb. Second, restricted microbial interactions by an expectant mother will bias the fetal immune system toward hypersensitivity. Here, we extend this discussion to hypothesize that the cell types sensing microbial exposures include fetal hematopoietic stem cells, which drive long-lasting changes to immunity

From traumatic childhood to cocaine abuse: the critical function of the immune system

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder (SUD), but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of SUD in individuals who have experience early life stress is unknown. Methods:In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early-life stress-induced susceptibility to the neurobehavioral effects of cocaine. Results: We provide evidence that exposure to social-stress (S-S) at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area (VTA) of S-S mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine (DA) neurons. Notably, preventing immune activation during the S-S exposure reverted the effects of DA in the VTA and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated Toll-like receptor 4-mediated innate immunity, an effect that was enhanced in cocaine addicts who had experienced a difficult childhood. Conclusions Collectively, our findings demonstrate that sensitization to cocaine in early-life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans

Early-Life Air Pollution Exposure, Neighborhood Poverty, and Childhood Asthma in the United States, 1990⁻2014.

Ambient air pollution is a well-known risk factor of various asthma-related outcomes, however, past research has often focused on acute exacerbations rather than asthma development. This study draws on a population-based, multigenerational panel dataset from the United States to assess the association of childhood asthma risk with census block-level, annual-average air pollution exposure measured during the prenatal and early postnatal periods, as well as effect modification by neighborhood poverty. Findings suggest that early-life exposures to nitrogen dioxide (NO₂), a marker of traffic-related pollution, and fine particulate matter (PM2.5), a mixture of industrial and other pollutants, are positively associated with subsequent childhood asthma diagnosis (OR = 1.25, 95% CI = 1.10⁻1.41 and OR = 1.25, 95% CI = 1.06⁻1.46, respectively, per interquartile range (IQR) increase in each pollutant (NO₂ IQR = 8.51 ppb and PM2.5 IQR = 4.43 µ/m³)). These effects are modified by early-life neighborhood poverty exposure, with no or weaker effects in moderate- and low- (versus high-) poverty areas. This work underscores the importance of a holistic, developmental approach to elucidating the interplay of social and environmental contexts that may create conditions for racial-ethnic and socioeconomic disparities in childhood asthma risk

Strain specific effects of low level lead exposure on associative learning and memory in rats.

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) rats. The present study examined the extent to which this differential effect of Pb on hippocampal gene expression might influence behavior. Animals (males and females) were tested in a trace fear conditioning paradigm to evaluate effects of Pb exposures (perinatal (PERI; gestation to postnatal day 21) or early postnatal (EPN; postnatal day 1 to day 21)) on associative learning and memory. All animals (Pb-exposed and non-Pb-exposed controls) showed normal acquisition of the conditioned stimulus (tone)-unconditioned stimulus (footshock) association. Long Evans rats showed a significant deficit in short- and long-term recall, influenced by sex and the timing of Pb exposure (PERI or EPN). In contrast, Pb exposure had no significant effect on memory consolidation or recall in any SD rats. These results further demonstrate the important influence of genetic background to the functional outcomes from developmental Pb exposure

Why does early childhood deprivation increase the risk for depression and anxiety in adulthood? A developmental cascade model

Abstract Background: Using data from the English & Romanian Adoptees (ERA) study we recently reported that early time-lmited exposure to severe institutional deprivation is associated with early onset and persistent neurodevelopmental problems and later onset emotional problems. Here we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. Methods: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity , exposure to adverse life events and functioning in work and interpersonal relationships. Results: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity and emotional problems were inconclusive. Conclusions: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model

Sun exposure drives Antarctic cryptoendolithic community structure and composition

AbstractThe harsh environmental conditions of the ice-free regions of Continental Antarctica are considered one of the closest Martian analogues on Earth. There, rocks play a pivotal role as substratum for life and endolithism represents a primary habitat for microorganisms when external environmental conditions become incompatible with active life on rock surfaces. Due to the thermal inertia of rock, the internal airspace of lithic substratum is where microbiota find a protected and buffered microenvironment, allowing life to spread throughout these regions with extreme temperatures and low water availability. The high degree of adaptation and specialization of the endolithic communities makes them highly resistant but scarsely resilient to any external perturbation and thus, any shifts in microbial community composition may serve as early-alarm systems of environmental perturbation, including climate change.Previous research concluded that altitude and distance from sea do not play as driving factors in shaping microbial abundance and diversity, while sun exposure was hypothesized as significant parameter influencing endolithic settlement and development. This study aims to explore our hypothesis that changes in sun exposure translate to shifts in community composition and abundances of main biological compartments (fungi, algae and bacteria) in the Antarctic cryptoendolithic communities. We performed a preliminary molecular survey, based on DGGE and qPCR tecniques, of 48 rocks with varying sun exposure, collected in Victoria Land along an altitudinal transect from 834 to 3100 m a.s.l.Our findings demonstrate that differences in sun radiation between north and south exposure influence temperature of rocks surface, availability of water and metabolic activity and also have significant impact on community composition and microbial abundance