Study of Food Factors in Relation to Regulation of the Anti-aging Protein SMP30

(JSNFS Award for Young Investigators (2024))

Abstract

Senescence marker protein-30 (SMP30), originally discovered in rat liver, is a marker of aging. Importantly, SMP30 expression decreases with age in a sex hormone-independent manner and suppresses oxidative stress. Previously, however, no studies have investigated the regulation of SMP30 expression by nutrients or phytochemicals. In the present study, we demonstrated that epigallocatechin gallate (EGCG) and resveratrol positively regulated SMP30 expression in rat hepatoma-derived Fao cells. Furthermore, treatment with tert-butyl hydroperoxide, an oxidation promoter, decreased the expression of SMP30, whereas EGCG treatment inhibited these effects both in vivo and in vitro. Also, RSV suppressed the substantial downregulation of SMP30 expression caused by oxidative stress and hydrogen peroxide, leading to release of accumulated lactate dehydrogenase. The present findings offer new perspectives on the anti-aging properties of EGCG and RSV. Finally, the effects of ascorbic acid (AsA) deficiency on the relationship between SMP30 and acute liver injury were investigated in osteogenic disorder Shionogi rats, which have a hereditary defect in AsA biosynthesis. Importantly, the level of SMP30 protein in extracellular vesicles (EVs) was significantly increased under conditions of AsA deficiency. These results suggest that the release of SMP30 in EVs under AsA deficiency is involved in acute-phase responses. The findings of this study offer new perspectives on the anti-aging properties of SMP30 as a food factor, and also suggest that SMP30 in EVs could be used as a biomarker.