Abstract
Decreased fetal nutrient delivery leads to developmental programming. We hypothesized that programming predisposes to premature brain and cardiac aging. We developed baboon offspring of mothers fed ad lib (control) or with reduced nutrition of 70% control diet during pregnancy and lactation, resulting in intrauterine growth restriction (IUGR). MRI data from 29 control (CTL) baboons (aged 4–22y; human equivalent 16–88y) were used to construct a reference curve for brain aging. We also studied IUGR baboons (8 male, 8 female) age 5.7 y and CTL offspring (8 male, 8 female), age 5.6 y with MRI to evaluate left ventricular (LV) and right ventricular (RV) functional parameters, normalized to body surface area. Premature brain aging by +2.7 y (p<0.01) occurred in young adult female IUGR offspring vs. CTL. Cardiac data are presented for CTL, IUGR, OLD, mean ± SEM: left ventricular ejection fraction (58 ± 3%, 45 ± 2%, 50 ± 3%), filling rate (88.8 ± 7.1mL/sm2, 63.5 ± 7.0mL/sm2, 62.0 ± 7.3mL/sm2), right ventricular ejection fraction (49 ± 2%, 32 ± 3%, 39 ± 3%) and stroke volume (26.5 ± 1.8mL/m2, 20.0 ± 1.8mL/m2, 17.5 ± 2.2mL/m2) were all decreased (p < 0.05) similarly in IUGR and OLD. To our knowledge these cohorts are the first to reveal both premature brain and cardiac functional aging by young adulthood resulting from developmental programming and IUGR in any species. Further studies across the life-course will determine progression of cardiac dysfunction. These and other multi-organ non-invasive in-vivo aging related biomarkers we are developing will reveal determinants of premature aging and aid the development of preventive interventions and pharmacological treatments on an individualized basis.