Abscisic acid ameliorates d-galactose -induced aging in mice by modulating AMPK-SIRT1-p53 pathway and intestinal flora

Abstract

Abscisic acid (ABA) is a plant hormone with various biological activities. Aging is a natural process accompanied by cognitive and physiological decline, and aging and its associated diseases pose a serious threat to public health, but its mechanisms remain insufficient. Therefore, the purpose of this study was to investigate the ameliorative effects of ABA on d-galactose (D-Gal)-induced aging in mice and to delve into its molecular mechanisms. Aging model was es-tablished by theintraperitoneal injection of D-Gal. We evaluated the oxidative stress by measuring superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) levels in serum. Proteins content in brain were determined by Western blot. D-Gal-induced brain damage was monitored by measuring the levels of acetylcholinesterase (AChE) content and hematoxylin-eosin staining (H&E). To evaluate the effects of ABA on aging, we measured the gut microbiota. The results demonstrated that ABA increased SOD, CAT and AChE, decreased MDA level. H&E staining showed that ABA could improve D-Gal-induced damage. In addition, ABA regulated the B-cell-lymphoma-2 (BCL-2) family and Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling pathway, while further regulating the acetylation of p53 protein by modulating the AMPK pathway and activating SIRT1 protein, thereby inhibiting the apoptosis of brain neurons and thus regulating the aging process. Interestingly, ABA improved the ratio of intestinal bacteria involved in regulating multiple metabolic pathways in the aging process, such as Bacteroides, Firmicutes, Lactobacillus and Ak-kermansia. In conclusion, the present study suggests that ABA may be responsible for improving and delaying the aging process by enhancing antioxidant activity, anti-apoptosis and regulating intestinal flora.