OBJECTIVE  To observe the improving effect and preliminary mechanism of Astragalus membranaceus on natural aging model based on different model organisms.

  METHODS  Non-rodent and rodent natural aging models were constructed, including three model organisms: Caenorhabditis elegans, Drosophila melanogaster and wild-type mice. Elegans and Drosophilae were divided into four groups: blank control group, low, medium and high dose groups of total extract of Astragalus membranaceus. The mice were divided into four groups: natural aging group, administration group, dirty cage aging group and dirty cage feeding plus administration group. The mice in the administration group were given the total extract of Astragalus membranaceus by gavage daily for 5 consecutive months. Elegans and drosophilae were fed until all of them died to calculate the life span and survival rate; the motor ability and pharyngeal pump frequency of elegans were evaluated. Being cultured after Day38, all drosophilae were exposed to UV irradiation for 15-30 min every 2 days until they all died to calculate their survival rate under UV stimulation. Cochineal intestinal transport and glucose absorption tests were used to evaluate the intestinal function of mice. Alcian blue periodic acid Schiff (AB-PAS) staining and Edu staining were used to observe the length of intestinal villi, the depth of crypt, the number of goblet cells, and the migration distance of intestinal stem cells in mice. The expression of related genes in the intestinal tract of mice was detected by qPCR. Paired-end sequencing analysis of small intestine contents DNA fragments was performed using the Illumina PE250 platform.

  RESULTS  Astragalus membranaceus could significantly improve the natural life span of elegans (P < 0.05), restore the movement ability (P < 0.05) and pharyngeal pump rate (P < 0.01), and reduce the accumulation of lipofuscin (P < 0.01). Under UV irradiation stimulation, the lifespan of Drosophila was significantly shortened (P < 0.05), while Astragalus membranaceus could significantly prolong the lifespan and improve the motor ability of male Drosophila in the middle of life under this stress state (P < 0.05). In addition, Astragalus membranaceus significantly improved the intestinal nutrition absorption function and transport function of mice (P < 0.05), as well as the morphology of intestinal villus (P < 0.01); increased the migration distance of intestinal stem cells (P < 0.001). The sequencing results of intestinal flora showed that the species diversity and richness of intestinal flora in aging mice decreased (P < 0.01); the bacterial abundance of Firmicutes reduced significantly (P < 0.05). Astragalus could significantly increase the abundance of Bacillus, unidentified Lactobacillus in aging mice (P < 0.05, P < 0.01).

  CONCLUSION  Astragalus membranaceus can prolong the life span of model organisms, improve the aging characteristics of natural aging mice, regulate the intestinal flora homeostasis and improve the activity of intestinal stem cells.