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

Freilich, Colin D.

doi:10.1080/19485565.2023.2260742

Cited by 4 publications

(3 citation statements)

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“…This evidence is consistent with the broad literature linking loneliness to multimorbidity and other adverse health outcomes (e.g., Hajek et al, 2020; O’Sullivan et al, 2022; Wang et al, 2023) and the more limited evidence that psychosocial adversities like loneliness relate specifically to accelerated epigenetic or biological aging (Beach et al, 2022; Galkin et al, 2022). Given the robust associations between loneliness and health, there has been interest in how loneliness “gets under the skin” to become biologically embedded and methylation has emerged as theoretically plausible (Freilich, 2023b). While there is preliminary evidence that EAA may mediate associations between loneliness and cognitive health (Lynch et al, 2023; Phillips, 2020), these results suggest mediation may not generalize to outcomes like multimorbidity.…”

Section: Discussionmentioning

confidence: 99%

“…This study's design and its analysis were not preregistered. Processed data and MPlus syntax and output are available at https://osf.io/znqmy/ (Freilich, 2023a). The larger MIDUS study protocol was reviewed and approved by the Education and Social/Behavioral Sciences and the Health Sciences Institutional Review Boards at the University of Wisconsin-Madison; the present study was exempt from an Institutional Review Board review because we used publicly available, deidentifiable data.…”

Section: Methods Transparency and Opennessmentioning

confidence: 99%

“…Some portion of the associations between loneliness and health likely also result from common upstream determinants such as overlapping genetic influences (Abdellaoui et al, 2019) and reverse causality (i.e., poor health influencing social functioning; Holt-Lunstad et al, 2015). However, common determinants, health behaviors, and demographic factors cannot account for the entire loneliness-mortality link, consistent with "loneliness alter(ing) physiology at a more fundamental level" (Freilich, 2023b;Luo et al, 2012, p. 912).…”

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confidence: 99%

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Loneliness, epigenetic age acceleration, and chronic health conditions.

Freilich,

Markon,

Cole

et al. 2024

Psychology and Aging

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Having associations with a range of adverse physical health outcomes including mortality, loneliness is increasingly recognized as a pressing public health concern, but the mechanisms studied to date do not yet explain all loneliness-related health risk. We sought to evaluate whether epigenetic influences on DNA methylation could help explain the relationship between loneliness and health. To do so, we first estimated associations between loneliness and epigenetic age acceleration (EAA) in a subsample of participants in the study of midlife in the United States (n = 1,310), before testing whether EAA mediated and/or moderated the association between loneliness and the onset of chronic health conditions in older adulthood (n = 445 completing longitudinal follow-ups). Greater loneliness was weakly associated with greater EAA in the Horvath, DunedinPACE, and GrimAge measures after accounting for demographic (0.08 ≤ β ≤ 0.11) and behavioral (0.06 ≤ β ≤ 0.08) covariates. Loneliness also predicted increases in chronic condition counts and these effects were more pronounced for individuals with higher DunedinPACE EAA values (interaction term β = 0.09, p = .009), suggesting possible synergistic impacts. EAA measures appear to be promising in helping to understand individual variations in the health impacts of loneliness, but the specific mechanisms involved require further research. Public Significance StatementLonely individuals face poorer health outcomes than nonlonely individuals. These data support the notion that loneliness is associated with accelerated epigenetic aging which may amplify the impact of loneliness on physical health in older adulthood.

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Section: Discussionmentioning

confidence: 99%

Section: Methods Transparency and Opennessmentioning

confidence: 99%

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confidence: 99%

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Loneliness, epigenetic age acceleration, and chronic health conditions.

Freilich,

Markon,

Cole

et al. 2024

Psychology and Aging

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Protein signatures associated with loneliness and social isolation: Plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization

Gong,

Preminger,

Steptoe

et al. 2025

Brain, Behavior, and Immunity

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Associations Between Loneliness, Epigenetic Aging, and Multimorbidity Through Older Adulthood

Freilich,

Markon,

Mann

et al. 2024

The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences

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Objectives Loneliness is a pressing public health concern, but the mechanisms by which it leads to declining physical health are uncertain. Prior work has begun to explore epigenetic pathways, with some evidence suggesting a link between loneliness and DNA methylation, though it is unclear whether epigenetic variation can help explain loneliness-health associations. Method Associations between loneliness and epigenetic age acceleration (EAA) were estimated, as well as the degree to which EAA mediated and moderated the association between loneliness and the development of chronic physical health conditions (multimorbidity) in older adulthood. The sample consisted of Health and Retirement Study (HRS) participants who provided blood draws and consented to methylation profiling (n=4,018). Results Baseline loneliness was associated with greater EAA in the GrimAge measure net of demographic and behavioral covariates (β=0.07, p=.003). Loneliness and GrimAge each predicted increasing condition counts, but there was no evidence of an interactive effect. The association between loneliness and increasing condition counts was, however, significantly mediated by GrimAge (indirect path β=0.020, p=.003). Discussion These results suggest that the impact of loneliness on multimorbidity may, in part, operate through DNA methylation. The specific intermediary, physiological mechanisms that are involved will require further research, but EAA measures like GrimAge are promising in helping to understand the health impacts of loneliness.

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

Cited by 4 publications

References 223 publications

Loneliness, epigenetic age acceleration, and chronic health conditions.

Loneliness, epigenetic age acceleration, and chronic health conditions.

Protein signatures associated with loneliness and social isolation: Plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization

Associations Between Loneliness, Epigenetic Aging, and Multimorbidity Through Older Adulthood

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