Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling

TLDR

Early‑life socioeconomic disadvantage has been linked to higher susceptibility to chronic diseases in later life, possibly because adversity programs biological systems that persist across decades. The study tests whether early‑life socioeconomic disadvantage programs lasting biological changes by profiling genome‑wide transcription in healthy adults with low versus high early‑life socioeconomic status. Genome‑wide transcriptional profiling was performed on healthy adults stratified by low or high early‑life socioeconomic status. Low early‑life SES is linked to a transcriptional signature of reduced glucocorticoid receptor activity and heightened adrenergic, NF‑κB, and IL‑6 signaling, indicating a glucocorticoid‑resistant, pro‑inflammatory phenotype that may drive long‑term allostatic wear and increase risk of age‑related chronic disease.

Abstract

Children reared in unfavorable socioeconomic circumstances show increased susceptibility to the chronic diseases of aging when they reach the fifth and sixth decades of life. One mechanistic hypothesis for this phenomenon suggests that social adversity in early life programs biological systems in a manner that persists across decades and thereby accentuates vulnerability to disease. Here we examine the basic tenets of this hypothesis by performing genome-wide transcriptional profiling in healthy adults who were either low or high in socioeconomic status (SES) in early life. Among subjects with low early-life SES, there was significant up-regulation of genes bearing response elements for the CREB/ATF family of transcription factors that conveys adrenergic signals to leukocytes, and significant down-regulation of genes with response elements for the glucocorticoid receptor, which regulates the secretion of cortisol and transduces its antiinflammatory actions in the immune system. Subjects from low-SES backgrounds also showed increased output of cortisol in daily life, heightened expression of transcripts bearing response elements for NF-kappaB, and greater stimulated production of the proinflammatory cytokine interleukin 6. These disparities were independent of subjects' current SES, lifestyle practices, and perceived stress. Collectively, these data suggest that low early-life SES programs a defensive phenotype characterized by resistance to glucocorticoid signaling, which in turn facilitates exaggerated adrenocortical and inflammatory responses. Although these response patterns could serve adaptive functions during acute threats to well-being, over the long term they might exact an allostatic toll on the body that ultimately contributes to the chronic diseases of aging.