Low birthweight is associated with epigenetic age acceleration in the first 3 years of life.

Background and objectives: The Developmental Origins of Health and Disease hypothesis posits that early life adversity is associated with poor adult health outcomes. Epidemiological evidence has supported this framework by linking low birthweight with adult health and mortality, but the mechanisms remain unclear. Accelerated epigenetic aging may be a pathway to connect early life experiences with adult health outcomes, based on associations of accelerated epigenetic aging with increased morbidity and mortality. Methodology: Sixty-seven mother-infant dyads were recruited in the eastern Democratic Republic of Congo. Birthweight data were collected at birth, and blood samples were collected at birth and follow-up visits up to age 3. DNA methylation data were generated with the Illumina MethylationEPIC array and used to estimate epigenetic age. A multilevel model was used to test for associations between birthweight and epigenetic age acceleration. Results: Chronological age was highly correlated with epigenetic age from birth to age 3 (r = 0.95, p < 2.2 × 10-16). Variation in epigenetic age acceleration increased over time. Birthweight, dichotomized around 2500 g, predicted epigenetic age acceleration over the first 3 years of life (b = -0.39, p = 0.005). Conclusions and implications: Our longitudinal analysis provides the first evidence for accelerated epigenetic aging that emerges between birth and age 3 and associates with low birthweight. These results suggest that early life experiences, such as low birthweight, may shape the trajectory of epigenetic aging in early childhood. Furthermore, accelerated epigenetic aging may be a pathway that links low birthweight and poor adult health outcomes.

The social patterning of vicarious discrimination: Implications for health equity.

BACKGROUND: Most research on discrimination and health operationalizes discrimination as direct individual experiences. Here, we examine the social patterning of vicarious discrimination, an important but largely overlooked dimension of discrimination. METHODS: Drawing on community-based participatory research with a multi-stage probability sample (n = 178) of African Americans in Tallahassee, Florida, we measured vicarious discrimination, or exposure to discrimination through one's family and friends. We used chi-square tests to examine gender differences in the social domains and relational sources of vicarious discrimination. Negative binomial regression models were fit to identify predictors of exposure to vicarious discrimination. RESULTS: Vicarious discrimination is more prevalent than direct experiences of discrimination (73 versus 61%) and more than 20% of participants report vicarious discrimination in the absence of direct discrimination. For women, vicarious discrimination most often involved the workplace; for men, police. However, gender differences are smaller for vicarious versus direct discrimination. Close friends and children were top relational sources of vicarious discrimination for men and women, respectively. Middle-aged participants reported the most vicarious discrimination. CONCLUSIONS: Overall, our data show that vicarious discrimination is more common than widely understood and associated with individual-level sociodemographic characteristics that index one's position in broader social systems. The prevalence of vicarious discrimination in the absence of direct discrimination suggests that standard approaches, which measure individual exposures in isolation, are subject to misclassification bias. Our results imply that existing research on discrimination and health, which already demonstrates substantial harm, underestimates African Americans' true exposures to salient aspects of discrimination.

Prenatal maternal stress is associated with site-specific and age acceleration changes in maternal and newborn DNA methylation.

Prenatal maternal stress has a negative impact on child health but the mechanisms through which maternal stress affects child health are unclear. Epigenetic variation, such as DNA methylation, is a likely mechanistic candidate as DNA methylation is sensitive to environmental insults and can regulate long-term changes in gene expression. We recruited 155 mother-newborn dyads in the Democratic Republic of Congo to investigate the effects of maternal stress on DNA methylation in mothers and newborns. We used four measures of maternal stress to capture a range of stressful experiences: general trauma, sexual trauma, war trauma, and chronic stress. We identified differentially methylated positions (DMPs) associated with general trauma, sexual trauma, and war trauma in both mothers and newborns. No DMPs were associated with chronic stress. Sexual trauma was positively associated with epigenetic age acceleration across several epigenetic clocks in mothers. General trauma and war trauma were positively associated with newborn epigenetic age acceleration using the extrinsic epigenetic age clock. We tested the top DMPs for enrichment of DNase I hypersensitive sites (DHS) and found no enrichment in mothers. In newborns, top DMPs associated with war trauma were enriched for DHS in embryonic and foetal cell types. Finally, one of the top DMPs associated with war trauma in newborns also predicted birthweight, completing the cycle from maternal stress to DNA methylation to newborn health outcome. Our results indicate that maternal stress is associated with site-specific changes in DNAm and epigenetic age acceleration in both mothers and newborns.

Maternal Psychosocial Stress Is Associated with Reduced Diversity in the Early Infant Gut Microbiome.

The developing infant gut microbiome is highly sensitive to environmental exposures, enabling its evolution into an organ that supports the immune system, confers protection from infection, and facilitates optimal gut and central nervous system function. In this study, we focus on the impact of maternal psychosocial stress on the infant gut microbiome. Forty-seven mother-infant dyads were recruited at the HEAL Africa Hospital in Goma, Democratic Republic of Congo. Extensive medical, demographic, and psychosocial stress data were collected at birth, and infant stool samples were collected at six weeks, three months, and six months. A composite maternal psychosocial stress score was created, based on eight questionnaires to capture a diverse range of stress exposures. Full-length 16S rRNA gene sequences were generated. Infants of mothers with high composite stress scores showed lower levels of gut microbiome beta diversity at six weeks and three months, as well as higher levels of alpha diversity at six months compared to infants of low stress mothers. Longitudinal analyses showed that infants of high stress mothers had lower levels of health-promoting Lactobacillus gasseri and Bifidobacterium pseudocatenulatum at six weeks compared to infants of low stress mothers, but the differences largely disappeared by three to six months. Previous research has shown that L. gasseri can be used as a probiotic to reduce inflammation, stress, and fatigue, as well as to improve mental state, while B. pseudocatenulatum is important in modulating the gut-brain axis in early development and in preventing mood disorders. Our finding of reduced levels of these health-promoting bacteria in infants of high stress mothers suggests that the infant gut microbiome may help mediate the effect of maternal stress on infant health and development.

Effect of a telephone and web-based problem-solving intervention for stroke caregivers on stroke patient activities of daily living: A randomized controlled trial.

OBJECTIVE: To test for effects of a problem-solving intervention for stroke caregivers on stroke survivor activities of daily living. DESIGN: Two-arm parallel randomized clinical trial with repeated measures at 11 weeks and 19 weeks. SETTING: Medical centers for US military Veterans. SUBJECTS: Caregivers of stroke survivors. INTERVENTION: A registered nurse guided caregivers in using problem-solving strategies emphasizing creative thinking, optimism, planning, and expert information to address challenges associated with caregiving. Caregivers in the intervention completed one telephone orientation session followed by eight online, asynchronous messaging center sessions. The messaging center sessions involved (a) education on the Resources and Education for Stroke Caregivers' Understanding and Empowerment website (https://www.stroke.cindrr.research.va.gov/en/), (b) supportive communication between the nurse and caregiver, (c) nurse and caregiver interactions to improve problem-solving, and (d) maintain adherence to discharge planning instructions. MAIN OUTCOME: The Barthel Index was used to measure activities of daily living. RESULTS: 174 participants (standard care n = 88, intervention n = 86) were enrolled at baseline. There were no significant differences between groups at baseline. Change scores in activities of daily living between baseline and 11 weeks were significantly higher in the intervention group than the standard care group (group difference = 6.43, 95% confidence interval: 1.28, 11.58). Group differences in change scores between baseline and 19 weeks were not statistically significant (group difference = 3.89, 95% confidence interval: -3.58, 11.36). CONCLUSIONS: This web-based caregiver intervention improved stroke survivor activities of daily living by 11 weeks, but intervention effects were undetectable after 19 weeks.

Associations between perceived discrimination and immune cell composition in the Jackson Heart Study.

African American adults suffer disproportionately from several non-communicable and infectious diseases. Among numerous contributing factors, perceived discrimination is considered a stressor for members of historically marginalized groups that contributes to health risk, although biological pathways are incompletely understood. Previous studies have reported associations between stress and both an up-regulation of non-specific (innate) inflammation and down-regulation of specific (adaptive) immunity. While associations between perceived discrimination and markers of inflammation have been explored, it is unclear if this is part of an overall shift that also includes down-regulated adaptive immunity. Relying on a large cross-section of African American adults (n = 3,319) from the Jackson Heart Study (JHS) in Jackson, Mississippi, we tested whether perceived everyday and lifetime discrimination as well as perceived burden from lifetime discrimination were associated with counts of neutrophils (innate), monocytes (innate), lymphocytes (adaptive), and the neutrophil-to-lymphocyte ratio (NLR), derived from complete white blood cell counts with differential. In addition, DNA methylation (DNAm) was measured on the EPIC array in a sub-sample (n = 1,023) of participants, allowing estimation of CD4T, CD8T and B lymphocyte proportions. Unexpectedly, high lifetime discrimination compared to low was significantly associated with lower neutrophils (b : -0.14, [95% CI: -0.24, -0.04]) and a lower NLR (b : -0.15, [95% CI: -0.25, -0.05]) after controlling for confounders. However, high perceived burden from lifetime discrimination was significantly associated with higher neutrophils (b : 0.17, [95% CI: 0.05, 0.30]) and a higher NLR (b : 0.16, [95% CI: 0.03, 0.29]). High perceived burden was also associated with lower lymphocytes among older men, which our analysis suggested might have been attributable to differences in CD4T cells. These findings highlight immune function as a potentially important pathway linking perceived discrimination to health outcomes.

Region-specific regulation of stem cell-driven regeneration in tapeworms.

Tapeworms grow at rates rivaling the fastest-growing metazoan tissues. To propagate they shed large parts of their body; to replace these lost tissues they regenerate proglottids (segments) as part of normal homeostasis. Their remarkable growth and regeneration are fueled by adult somatic stem cells that have yet to be characterized molecularly. Using the rat intestinal tapeworm, Hymenolepis diminuta, we find that regenerative potential is regionally limited to the neck, where head-dependent extrinsic signals create a permissive microenvironment for stem cell-driven regeneration. Using transcriptomic analyses and RNA interference, we characterize and functionally validate regulators of tapeworm growth and regeneration. We find no evidence that stem cells are restricted to the regeneration-competent neck. Instead, lethally irradiated tapeworms can be rescued when cells from either regeneration-competent or regeneration-incompetent regions are transplanted into the neck. Together, the head and neck tissues provide extrinsic cues that regulate stem cells, enabling region-specific regeneration in this parasite.