Fig. 4.

L2-Cmu prevents age-related diastolic dysfunction in females. a–c Cardiac aging in CB6F1 female mice is characterized by a decline in diastolic function (E/A ratio), increased LVPWd, and accumulating amounts of fibrosis in the myocardium. However, 6 mo L2-Cmu treatment, beginning at 78 wks of age, was able to preserve diastolic function, reduce LVPWd measures in females [Young (n = 6), Old Con (n = 8), and Old mAb (n = 7)], and largely prevented the accumulation of cardiac fibrosis [Young (n = 4), Old Con (n = 5), and Old mAb (n = 6)]. d Metabolomic analysis of heart tissue in female mice [Young (n = 7), Old Con (n = 8), and Old mAb (n = 7)] revealed that the young and aged metabolome are distinct (see also Supplementary Fig. 5), and predominantly characterized by differences in glycerophospholipids, and to a lesser extent ceramides, while amino acids, biogenic amines, and acylcarnitines were largely unaffected. However, mAb treatment tended to oppose the age-related alterations in several metabolites, including the rise of several glycerophospholipids, resulting in a more youthful metabolomic signature in heart. Further metabolomic data analyses can be found in in Supplementary Fig. 5 and the dataset here: [10.17605/OSF.IO/8QGX9]. e–g Remarkably, the favorable effects of L2-Cmu in males were absent for E/A ratio [Young (n = 5), Old Con (n = 6), and Old mAb (n = 5)] and fibrosis [Young (n = 8), Old Con (n = 8), and Old mAb (n = 8)], suggesting that the beneficial effects of modulating IGF-1 signaling in heart is specific to females. Bars represent mean ± s.e.m. Dot plots overlaid on bar graphs represent individual data points. Different letters denote a significant difference between groups by Tukey HSD, P ≤ 0.05