Aging and IGF-I: Relationships with Vitamin D and Body Composition. A Mediation Analysis

Roberto Vicinanza^1,2*Alessandro Frizza²Julie A Pollard¹Valentina Mazza²Massimo Ulderico De Martino³Giovanni Imbimbo²Pasquale Pignatelli²Evaristo Ettorre²Maria Del Ben²Alessio Molfino²

• ¹University of Southern California, Los Angeles, United States
• ²Sapienza University of Rome, Rome, Lazio, Italy
• ³University of Salerno, Fisciano, Campania, Italy

Background: Insulin-like Growth Factor I (IGF-I) and Vitamin D are crucial for growth and metabolism, with their levels declining with age. However, their mutual interactions and contributions to body composition remain unclear.To examine the relationships between IGF-I, Vitamin D, and body composition in geriatric outpatients, and to test the mediational role of IGF-I in the association between Vitamin D and Fat-Free Mass (FFM).Methods: 130 patients were eligible at the Geriatric Outpatient Clinic at the Policlinico Umberto I, Sapienza University of Rome, Italy. Multimorbidity was evaluated with the Cumulative Illness Rating scale for Geriatrics (CIRS-G). Body composition was measured using bioelectrical impedance analysis. Complete blood count, metabolic panel, IGF-I, and 25(OH) Vitamin D were assessed.Results: 91 patients were included in the analysis. Mean age was 74.4 ± 7.2 years; 50.5% female. Mean BMI was 28 kg/m 2 ± 3.9. Mean CIRS-G total score was 14.14 ± 4.1, and Severity Index (SI) was 1.16 ± 0.32. Median IGF-I was 122.0 ng/mL (IQR, 69.8) with higher levels in males compared to females (p = 0.0096). Mean 25(OH) Vitamin D was 27.04 ng/mL ± 14.69 with no significant sex difference. Level of 25(OH) Vitamin D positively correlated with IGF-I (ρ = 0.317, p = 0.003), while no correlation was found between Vitamin D and body composition parameters. Patients with higher IGF-I exhibited higher Total Body Water (TBW) (p = 0.024), Intracellular Water (ICW) (p = 0.018), FFM (p=0.022), and Muscle Mass (MM) (p=0.017), Body Cell Mass (BCM) (p=0.046). Linear regression analysis showed IGF-I and male sex predicted FFM (B=13.933, p<0.001; B = 0.040; p = 0.034; respectively). The mediation analysis confirmed no significant direct effect of Vitamin D on FFM (direct effect, B = -0.058, p = 0.319, 95% CI: -0.175, 0.058); however, the effect was significant when mediated by IGF-I (indirect effect, B = 0.039, SE = 0.022, 95% CI: 0.005, 0.091).Conclusions: These findings provide further evidence of a positive correlation between IGF-I and lean body mass and suggest that IGF-I may mediate the physiological effect of Vitamin D on FFM, highlighting their potential roles in assessing pre-frailty and personalizing nutrition interventions.