How does loneliness “get under the skin” to become biologically embedded?

ABSTRACT

Loneliness is linked to declining physical health across cardiovascular, inflammatory, metabolic, and cognitive domains. As a result, loneliness is increasingly being recognized as a public health threat, though the mechanisms that have been studied do not yet explain all loneliness-related health risk. Potential mechanisms include loneliness having 1.) direct, causal impacts on health, possibly maintained by epigenetic modification, 2.) indirect effects mediated through health-limiting behaviors, and 3.) artifactual associations perhaps related to genetic overlap and reverse causation. In this scoping review, we examine the evidence surrounding each of these pathways, with a particular emphasis on emerging research on epigenetic effects, in order to evaluate how loneliness becomes biologically embedded. We conclude that there are significant gaps in our knowledge of how psychosocial stress may lead to physiological changes, so more work is needed to understand if, how, and when loneliness has a direct influence on health. Hypothalamic-pituitary adrenocortical axis disruptions that lead to changes in gene expression through methylation and the activity of transcription factor proteins are one promising area of research but are confounded by a number of unmeasured factors. Therefore, wok is needed using causally informative designs, such as twin and family studies and intensively longitudinal diary studies.

Disclosure statement

We have no known conflict of interest to disclose.

Notes

¹ The primary databases used for the search were PubMed, Google Scholar, and PsycNet. The literature search was conducted between January and May 2023, but given the broad scope of the topic, there is a possibility that the search was not exhaustive.

² When considering epigenetics, transcriptomics, and telomeres, literature was reviewed on both loneliness and related constructs (e.g., relational support) while, when evaluating other pathways, the review focuses primarily on loneliness.

³ As a result, second-generation clocks may be used in empirical research more commonly, but it could be argued that by not being trained on age alone, they index a more general biological health construct, rather than strictly age acceleration.

⁴ Some recent work has been consistent in finding loneliness predicts decreased physical activity in the future (e.g., Yang et al. 2022) though null associations have been reported as well (Kobayashi and Steptoe 2018; Schrempft et al. 2019).

Additional information

Funding

CDF was supported by the National Institute on Drug Abuse (T32DA050560).