Anti-aging effects of oligomeric proanthocyanidins isolated from persimmon fruits.

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. The expression of phosphorylated neurofilament-H was significantly elevated in the hippocampal CA1. This indicates that oligomers induce an increase in the density of axons. To investigate the protective mechanisms of oligomers against brain dysfunction with aging, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more markedly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with aging and VEGFR-2 signaling may provide new suggestions for protection against memory deficit in the aging brain. In addition, we revealed that the administration of oligomers extended the life span of SAMP8. Oligomers elevated SIRT1 expression, which is recognized as an essential factor for life span extension in the brain. However, the administration of oligomers did not induce stereotypical behaviors such as rearing, jumping, or hanging from the lid of a cage, while food restriction increased these frequencies without a significant change in motor function. The present study suggests the promising role of oligomers as an anti-aging agent to extend life span.