Associations of Early-Life Adversity With Later-Life Epigenetic Aging Profiles in the Multi-Ethnic Study of Atherosclerosis.

Epigenetic biomarkers of accelerated aging have been widely used to predict disease risk and may enhance our understanding of biological mechanisms between early-life adversity and disparities in aging. With respect to childhood adversity, most studies have used parental education or childhood disadvantage and/or have not examined the role played by socioemotional or physical abuse and trauma in epigenetic profiles at older ages. This study leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA) on experiences of threat and deprivation in participants' early lives (i.e., before the age of 18 years) to examine whether exposure to specific dimensions of early-life adversity is associated with epigenetic profiles at older ages that are indicative of accelerated biological aging. The sample included 842 MESA respondents with DNA methylation data collected between 2010 and 2012 who answered questions on early-life adversities in a 2018-2019 telephone follow-up. We found that experiences of deprivation, but not threat, were associated with later-life GrimAge epigenetic aging signatures that were developed to predict mortality risk. Results indicated that smoking behavior partially mediates this association, which suggests that lifestyle behaviors may act as downstream mechanisms between parental deprivation in early life and accelerated epigenetic aging in later life.

Endothelial activation and cell adhesion molecule concentrations in pregnant women living at high altitude.

OBJECTIVES: Maternal physiology at high altitude could be considered to resemble an intermediate state between preeclampsia and normal pregnancy. The objective of the current study was to determine if cell adhesion molecules, known to be increased in preeclampsia, are increased with chronic maternal and placental hypoxia (due to high-altitude residence) in the absence of preeclampsia. METHODS: Serum was collected from women residing at 3100 m or 1600 m in the three trimesters of pregnancy and postpartum. Vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: General linear model (GLM) repeated measures analysis of VCAM-1, E-selectin, and ICAM-1 data showed there were no statistically significant effects of gestation within either the high- or moderate-altitude groups or between the different altitudes. CONCLUSION: The increase in cell adhesion molecules reported in preeclampsia is not present in pregnant women at high altitude, suggesting that maternal systemic hypoxia is not responsible for this pathway of endothelial cell activation in preeclampsia.

Villous explant culture: characterization and evaluation of a model to study trophoblast invasion.

The mechanisms that control invasion of cytotrophoblast (CTB) cells into the maternal decidua and myometrium with transformation of the maternal spiral arteries are not fully understood, but oxygen is thought to be a key factor. We carried out a semiquantitative evaluation of an explant culture model for use in the study of trophoblast proliferation and invasion. Explants of human villous tissue (6-9 weeks of gestation) cultured on Matrigel in both standard culture conditions (18% O2) and in a low oxygen environment (2% O2) produced regions of outgrowth, of cytotrophoblast cells from villous tips and migration of cells into the Matrigel. The number of sites of outgrowth and migration, area of outgrowth, and extent of migration of cells into the Matrigel tended to increase throughout the culture period (144 h) but varied between explants from the same placenta and those from different placentas. There were no significant differences in the number of sites of outgrowth or migration scores in explants cultured in a low oxygen environment compared to those cultured in standard conditions. This study highlights the importance of careful validation, design and interpretation of experiments using in vitro culture systems, particularly those investigating the regulatory role of oxygen.