Effect of Intentional Weight Loss on Mortality Biomarkers in Older Adults With Obesity

Observational research has identified several mortality biomarkers; however, their responsiveness to change is unknown. We tested whether the Healthy Aging Index (HAI) and other mortality biomarkers were responsive to intentional weight loss (WL), which is associated with lower mortality risk in recent meta-analyses. Older adults (70.3 ± 3.7 years) with obesity were randomized into a 6-month WL (n = 47) or weight stability (WS: ±5% baseline weight; n = 48) program. Baseline and 6-month HAI score (0-10) was calculated from component sum (each 0-2: systolic blood pressure, forced vital capacity [FVC], creatinine, fasting blood glucose [FBG], Montreal Cognitive Assessment), and gait speed, grip strength, Digit Symbol Substitution Test, FEV1, Interleukin-6, C-Reactive Protein, and Cystatin-C were assessed at baseline and 6 months. Mean baseline HAI was 3.2 ± 1.6. By 6 months, WL participants lost 8.87 (95% CI: -10.40, -7.34) kg, whereas WS participants remained weight stable. WL group reduced HAI score (WL: -0.75 [95% CI: -1.11, -0.39] vs WS: -0.22 [95% CI: -0.60, 0.15]; p = .04), and components changing the most were FBG (WL: -3.89 [95% CI: -7.78, 0.00] mg/dL vs WS: 1.45 [95% CI: -2.61, 5.50] mg/dL; p = .047) and FVC (WL: 0.11 [95% CI: -0.01, 0.23] L vs WS: -0.05 [95% CI: -0.17, 0.08] L; p = .06). Among other biomarkers, only Cystatin-C significantly changed (WL: -2.53 [95% CI: -4.38, -0.68] ng/mL vs WS: 0.07 [95% CI: -1.85, 1.98] ng/mL; p = .04). Combining treatment groups, 1 kg WL was associated with a 0.07 (95% CI: 0.03, 0.12) HAI reduction (p < .01). Intentional WL via caloric restriction reduced HAI score by 0.53 points, largely attributable to metabolic and pulmonary improvements.