Ethnicity SNI 0 SNI 1 Age-Gap SNI 2 SNI 3 SNI 4 bination with demographic and medical conditions, is a signicant risk factor for accelerated aging. However, the contribution of each component in Age-Gap White Non-White P value 0.4 (cid:1) 9.8 2.1 (cid:1) 10.3 <0.001 0.6 (cid:1) 9.4 2.1 (cid:1) 9.8 <0.001 0.001 (cid:1) 9 1.3 (cid:1) 9.9 <0.001 (cid:3)1.05 (cid:1) 8.9 0.7 (cid:1) 9.8 <0.001 (cid:3)1.3 (cid:1) 8.4 (cid:3)0.2 (cid:1) 9 <0.001 prediction varied across different age groups. addition, survival analysis indicated the association between social isolation and a higher mortality rate. Values are mean (cid:1) SD. Thus, the current study highlights the role of social SNI Social Network Index. In J A C C : A D V A N C E S , V O L . , N O . , 2 0 2 4 2 0 2 4 : 1 0 0 8 9 0 Rajai et al

Association Between Social Isolation and Biological Aging T A B L E 4 Univariable and Multivariable Regression Analysis of the Association Between Social Isolation and Age-Gap Univariable Multivariable Beta 95% CI P Value Beta 95% CI P Value Chronological age SNIa (SNI 0) (cid:3)0.32 (cid:3)0.32 to (cid:3)0.32 <0.001 (cid:3)0.33 (cid:3)0.33 to (cid:3)0.33 <0.001 1 2 3 4 Sex BMI Diabetes Ever smoking Alcohol use disorder Hypertension Hyperlipidemia Myocardial infarction Congestive heart failure Peripheral vascular disease Atrial brillation Cerebrovascular disease Chronic pulmonary disease Chronic kidney disease

Cancer 0.13 (cid:3)0.52 (cid:3)1.5 (cid:3)1.9 0.98 0.12 (cid:3)1.2 0.02 2.6 (cid:3)2.5 (cid:3)2.7 (cid:3)2.2 (cid:3)1.5 (cid:3)2.5 (cid:3)2.6 (cid:3)3.0 (cid:3)0.27 (cid:3)1.6 (cid:3)2.2 (cid:3)0.02 to 0.27 (cid:3)0.66 to (cid:3)0.38 (cid:3)1.7 to (cid:3)1.4 (cid:3)2.0 to (cid:3)1.7 0.91 to 1.0 0.11 to 0.12 (cid:3)1.3 to (cid:3)1.1 (cid:3)0.06 to 0.11 2.4 to 2.7 (cid:3)2.6 to (cid:3)2.4 (cid:3)2.8 to (cid:3)2.6 (cid:3)2.5 to (cid:3)2.0 (cid:3)1.6 to (cid:3)1.4 (cid:3)2.6 to (cid:3)2.3 (cid:3)2.7 to (cid:3)2.4 (cid:3)3.2 to (cid:3)2.9 (cid:3)0.38 to (cid:3)0.16 (cid:3)1.7 to (cid:3)1.4 (cid:3)2.4 to (cid:3)2.0 0.081 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.6 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.09 0.13 (cid:3)0.15 (cid:3)0.11 0.11 0.07 0.26 0.11 0.82 0.77 (cid:3)0.28 (cid:3)0.01 0.94 0.28 1.3 (cid:3)0.21 0.49 0.94 (cid:3)0.54 (cid:3)0.03 to 0.21 (cid:3)0.02 to 0.25 (cid:3)0.27 to (cid:3)0.03 (cid:3)0.22 to (cid:3)0.01

0.06 to 0.17 0.07 to 0.08 0.16 to 0.35 0.04 to 0.19 0.69 to 0.95 0.70 to 0.84 (cid:3)0.38 to (cid:3)0.18 (cid:3)0.19 to 0.17 0.81 to 1.1 0.16 to 0.39 1.2 to 1.4 (cid:3)0.35 to (cid:3)0.07 0.20 to 0.78 0.81 to 1.1 (cid:3)0.70 to (cid:3)0.37 0.14 0.02 0.01 <0.001 <0.001 <0.001 <0.001 0.002 <0.001 <0.001 <0.001 >0.9 <0.001 <0.001 <0.001 0.004 <0.001 <0.001 <0.001 aSocial Network Index, the reference level for sex was female, for SNI was 0,1 and for comorbidities was not having the condition. CI condence interval; BMI body mass index. F I G U R E 2 Comparison of Cumulative Hazard Ratios of Social Network Index in Predicting Mortality 7 8 Rajai et al Association Between Social Isolation and Biological Aging T A B L E 5 The Result of Cox Proportional Hazard Analysis for the Association Between Social Connection and All-Cause Mortality Cox Proportional Hazard Unadjusted Model Adjusted Modela HR 95% CI P Value HR 95% CI P Value SNI 0 (reference)