Relationship Between Social Isolation, Loneliness, and Systemic Inflammation: A Scoping Review of Biological Signatures and Clinical Outcomes.

Authors

Aimilia Bechliouli, Dimitrios Stylianakis, Marios Spanakis, Christos Lionis, Emmanouil K Symvoulakis

Published in

Diseases (Basel, Switzerland). Volume 14. Issue 10. Oct 21, 2026. Epub Oct 21, 2026.

Abstract

Social isolation and loneliness are established social determinants of health, associated with 25-30% higher mortality risk, yet their relationship with systemic inflammation and broader biological and clinical outcomes has not been comprehensively synthesized across life stages.
PubMed/MEDLINE, Scopus, and ScienceDirect were searched (2015-2025), supplemented by citation searching and a targeted supplementary search, for human studies linking social isolation, loneliness, or social connectedness to inflammatory biomarkers or biological/clinical outcomes. PRISMA-ScR guidance was followed; findings were synthesized narratively across five thematic axes as an evidence map.
Of 3351 records identified, 73 studies were included. Isolation was most often associated with CRP and fibrinogen, and loneliness with IL-6. Isolation predicted sarcopenia, venous thromboembolism, pancreatic cancer, and cardiovascular disease, with inflammatory or metabolic markers mediating a modest (≈5-19%) share. Proteomic (n = 42,062) and epigenetic analyses linked loneliness to inflammatory, antiviral, and complement-pathway proteins and to accelerated epigenetic ageing; Mendelian randomization supported causal involvement of several proteins. Social connectedness and relationship quality tracked with lower IL-6 and better functional indices. Evidence was strongest in midlife and older cohorts.
Social disconnection shows biologically plausible but heterogeneous associations with inflammatory and molecular signatures; harmonized measurement and prospective, hypothesis-free omics designs are needed to clarify causality and inform targeted screening.

PMID:
42930015
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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