Epigenetics refers to changes to the structure of DNA that affect patterns of gene expression without modifying the primary nucleotide sequence. Methylation of cytosine residues within CpG dinucleotides (5-methyl-cytosine) is one of several known epigenetic and a vast literature characterizes CpG sites and/or genomic regions that become either hypermethylated or hypomethylated with increasing age, suggesting a role for DNA methylation in biological aging.

The catecholamines norepinephrine (NE) and epinephrine (EPI) are of great epidemiological and clinical relevance, being key neurotransmitters specifically involved in acute stress-pathway activation. This contribution to the Stress Measurement Network focusses on the measurement, analysis and interpretation of NE and EPI, as well as their metabolites’, and their applicability in population-based, basic, translational and clinical research settings. The entry further informs about methodology currently available for the measurement of NE and EPI (and related metabolites) in human plasma and urine, the importance of sample collection, preparation and finally specific considerations and limitations.

Our genes are comprised of DNA, but those DNA genes only influence cellular function, health, and behavior if they are transcribed into RNA, or “expressed.” Only a subset of our ~20,000 genes are actively transcribed in any given cell, and which genes are “on” and “off” determines not only the identity of the cell but its functional capacities and behavior. As such, RNA “transcriptome profiling” has become the dominant method for analyzing the molecular underpinnings of healthy physiology, development, aging, and disease. Research has also found that social and psychological processes can influence RNA profiles. RNA profiling thus provides a useful method for mapping the molecular interface between social and behavioral processes and the biology of health and aging.

The neuroendocrine and immune systems play a major role in adaptation to stress. Glucocorticoids secreted as end hormones of the hypothalamus-pituitary-adrenal (HPA) axis belong to the most frequently used biological outcomes in stress research. This is based on their dynamic response to acute situations, and changes of their circadian secretion in some conditions of chronic psychological stress, and on their effects on target tissues throughout the body, which are involved in regulating body homeostasis at rest and in conditions of stress.

This summary focuses on the measurement of the hormone cortisol in hair. Hair cortisol provides information regarding longer-term (weeks to months) cortisol exposure levels. We highlight why hair cortisol analysis advances neuroendocrine research for several reasons.

There is fairly consistent evidence that stress, both acute and chronic, is related to elevated levels of inflammatory activity despite the fact that inflammation is a fundamental immune process for maintaining survival in that it serves as the body’s natural response to insult or injury. This summary describes the various options for inflammation in studies of stress.

Pace of biological aging refers to the rate at which an individual experiences aging-related decline in system integrity, a cause of increased vulnerability to development of chronic disease, onset of disability, and mortality. A variety of methods are proposed to quantify the pace of biological aging and no gold-standard measurement exists. The most robust methods currently available utilize algorithms that combine information from multiple biomarkers of organ-system integrity or from DNA methylation marks at dozens or hundreds of sites across the genome. 

The autonomic nervous system (ANS) functions to mobilize energy and deliver oxygenated-blood to the body. The ANS changes during sleeping and waking states, postural changes, and physical movement. Moreover, ANS changes occur during mental states such as stress, emotion, cognitive, and motivation. This document provides an overview of some of the more commonly used measures in stress studies that can be obtained relatively non-invasively. We describe the process of obtaining ANS responses including technological requirements for lab and field experiments, and the specifics of obtaining, scoring, quantifying, analyzing, and interpreting ANS responses.

The hypothalamic-pituitary adrenal (HPA) axis has been proposed to play a key role in stress-health linkages. Thus, interest in the HPA axis has been strong and has exploded over the past decade with the availability of low-cost cortisol measurement in saliva. This allowed cortisol assessment in population-based and epidemiological research, providing valuable evidence on links between salivary cortisol with job stress, trauma, depression, socioeconomic and demographic status, negative health outcomes, metabolic disease, and cancer mortality.

The skin is the interface between an organism and the outside world. External factors, such as cold, dryness, air pollution and UV radiation impact the skin in predictable ways. However, while psychological stress long has been recognized as an exacerbating factor in many skin conditions, we now are just beginning to understand possible mechanisms that may underlie this process.

Stress contagion refers to the idea that intrapersonal affective experiences can influence others in our social network and people can "catch" the stress of others. Researchers have used a variety of approaches with the goal of detecting stress contagion using measures of peripheral physiology that are non-obtrusive and continuous.

Immune cell telomere length has become a common biomarker in health studies because it reliably predicts later onset of several diseases such as cardiovascular disease, it’s mechanisms of disease are understood, and it is easy to measure with blood. It is also associated with the wide range of exposome factors–chemicals, pollution, neighborhood safety, stressor exposures, and lifestyle.