Regulation of transglutaminase-2 and related miRNAs expression by calorie restriction in aorta of aging female mice.

Background: Transglutaminase-2 (TG2) plays a key role in age-related vascular stiffness. This study aims to evaluate the effects of calorie restriction (CR) on TG2 mRNA and protein levels and identify differentially expressed microRNAs (miRNA) predicted to target TG2.

Methods And Results: Female mice were assigned to ad libitum (AL), chronic CR (CCR), and intermittent CR (ICR) groups for 80 weeks. Expression levels of miRNAs predicted to target TG2 (miR-423-5p, miR-700-5p, miR-484, miR-7048-5p, and miR-7053-5p) were identified in blood and aorta samples. TG2 mRNA expression levels in the aorta were analyzed. A similar trend was observed between blood and aorta samples for miR-423-5p, miR-484, and miR-700-5p. TG2 mRNA expression was significantly lower in the ICR-R group compared to the AL group. TG2 protein levels  in aorta were lower in the CCR group than that of in the AL group in old age. Endothelial nitric oxide synthase (eNOS) protein levels were also determined owing to their role in NO-dependent TG2 regulation and were lowest in the CCR group, with an overall decline in aging mice.

Conclusions: The CR intervention reveals protective potential against vascular stiffness, as TG2 levels were lower in the aorta of aging CR mice. These findings provide translational insights into the epigenetic regulation of TG2 by CR in vascular aging.