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. 2025 May 3;37(1):140.
doi: 10.1007/s40520-025-03041-4.

Social isolation, loneliness and the relationship with serum biomarkers, functional parameters and mortality in older adults

Stefanie Braig  1 , Michael D Denkinger  2   3 , Dhayana Dallmeier  2   4 , Jochen Klenk  5   6 , Dietrich Rothenbacher  5 ; ActiFE Study Group
Affiliations

Social isolation, loneliness and the relationship with serum biomarkers, functional parameters and mortality in older adults

Stefanie Braig et al. Aging Clin Exp Res. .

Abstract

Background: Pathways between social isolation (SI), loneliness and health are unclear.

Aims: To analyze the relationship between SI and loneliness with biomarkers of inflammation, cardiac and immune function, functional parameters, and mortality.

Methods: SI (Lubben Social Network Scale) from family, friends, and overall as well as loneliness (single direct question) were assessed at baseline in a population-based cohort study of 1459 community-dwelling adults aged 65 + in Germany. Serum biomarkers and functional parameters measured at baseline and at three-year follow-up included high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-cTnI), high-sensitivity troponin T (hs-cTnT), gait speed, and hand grip strength. We used linear and Cox regression analyses adjusted for age and sex (model 1) and established confounders (model 2).

Results: High SI from friends was associated with small but significant adverse associations with some biomarkers (hs-CRP, GDF-15, hs-cTnT) at follow-up (model 1). High SI from family associated with NT-proBNP (model 2), high SI and moderate to severe loneliness with lower gait speed. Loneliness was linked to hs-CRP at baseline, but SI was a stronger predictor of biomarker levels. High SI overall (Hazard ratio 1.39, 95% CI 1.15; 1.67, model 2) was associated with increased 10-year mortality.

Discussion: Mainly SI from friends is linked to unfavorable biomarker profiles with small associations. Overall SI was negatively associated with functional parameters and positively with mortality.

Conclusions: Further research should confirm our findings using, e.g. a multidimensional assessment of loneliness.

Keywords: Biomarkers; Cardiac markers; Loneliness; Mortality; Social isolation.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The study was conducted according to the Declaration of Helsinki. The Ethics Committee of Ulm University had approved the study (application no. 318/08 and 50/12). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Participants signed informed consent regarding publishing their data.

Figures

Fig. 1
Fig. 1
Flow chart of study participants from baseline to follow-up
Fig. 2
Fig. 2
Panel 1: associations between social isolation or loneliness and inflammatory markers (regression coefficients with 95% confidence intervals). a versus not socially isolated from the respective group (i.e. family, friends, or overall); GFR Cystatin C based glomerular filtration rate [ml/min], hs-CRP high-sensitivity C reactive protein, IL-6 interleukin 6, SI social isolation; IL-6 at follow-up not applicable. Panel 2: associations between social isolation or loneliness and cardiac markers (regression coefficients with 95% confidence intervals). GDF-15 growth/differentiation factor 15, NT-proBNP N-terminal pro-brain natriuretic peptide, hs-cTnI high-sensitivity troponin I, hs-cTnT high-sensitivity troponin T.Panel 3: associations between social isolation or loneliness and functional parameters (regression coefficients with 95% confidence intervals).
Fig. 2
Fig. 2
Panel 1: associations between social isolation or loneliness and inflammatory markers (regression coefficients with 95% confidence intervals). a versus not socially isolated from the respective group (i.e. family, friends, or overall); GFR Cystatin C based glomerular filtration rate [ml/min], hs-CRP high-sensitivity C reactive protein, IL-6 interleukin 6, SI social isolation; IL-6 at follow-up not applicable. Panel 2: associations between social isolation or loneliness and cardiac markers (regression coefficients with 95% confidence intervals). GDF-15 growth/differentiation factor 15, NT-proBNP N-terminal pro-brain natriuretic peptide, hs-cTnI high-sensitivity troponin I, hs-cTnT high-sensitivity troponin T.Panel 3: associations between social isolation or loneliness and functional parameters (regression coefficients with 95% confidence intervals).
Fig. 2
Fig. 2
Panel 1: associations between social isolation or loneliness and inflammatory markers (regression coefficients with 95% confidence intervals). a versus not socially isolated from the respective group (i.e. family, friends, or overall); GFR Cystatin C based glomerular filtration rate [ml/min], hs-CRP high-sensitivity C reactive protein, IL-6 interleukin 6, SI social isolation; IL-6 at follow-up not applicable. Panel 2: associations between social isolation or loneliness and cardiac markers (regression coefficients with 95% confidence intervals). GDF-15 growth/differentiation factor 15, NT-proBNP N-terminal pro-brain natriuretic peptide, hs-cTnI high-sensitivity troponin I, hs-cTnT high-sensitivity troponin T.Panel 3: associations between social isolation or loneliness and functional parameters (regression coefficients with 95% confidence intervals).
Fig. 2
Fig. 2
Panel 1: associations between social isolation or loneliness and inflammatory markers (regression coefficients with 95% confidence intervals). a versus not socially isolated from the respective group (i.e. family, friends, or overall); GFR Cystatin C based glomerular filtration rate [ml/min], hs-CRP high-sensitivity C reactive protein, IL-6 interleukin 6, SI social isolation; IL-6 at follow-up not applicable. Panel 2: associations between social isolation or loneliness and cardiac markers (regression coefficients with 95% confidence intervals). GDF-15 growth/differentiation factor 15, NT-proBNP N-terminal pro-brain natriuretic peptide, hs-cTnI high-sensitivity troponin I, hs-cTnT high-sensitivity troponin T.Panel 3: associations between social isolation or loneliness and functional parameters (regression coefficients with 95% confidence intervals).
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