Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly populations, whereas there is no cure for PD so far. Novel animal models and medications await development to elucidate the aetiology of PD and attenuate the symptoms, respectively. Methods: A neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was used in the current study to establish a PD pathologic model in silkworms. The time required to complete specific behaviours was recorded. Dopamine content was detected by ultra-performance liquid chromatography (UPLC). The activity of insect tyrosine hydroxylase (TH) was determined using a double-antibody sandwich method. Oxidative stress was assessed by changes in antioxidant enzyme activity and the content of oxidative products. Results: MPTP-treated silkworms were characterized by impaired motor ability, reduced dopamine content, and elevated oxidative stress level. The expression of TH, a dopamine biosynthetic enzyme within dopaminergic neurons in the brain, was significantly reduced, indicating that dopaminergic neurons were damaged. Moreover, MPTP-induced motility impairment and reduced dopamine level in the silkworm PD model could be rescued after feeding a combination of levodopa (L-dopa [LD]) and carbidopa (CD). MPTP-induced oxidative damage was also alleviated, in ways consistent with other PD animal models. Interestingly, administration of Lycium barbarum polysaccharide (LBP) improved the motor ability, dopamine level, and TH activity, and the oxidative damage was concomitantly reduced in the silkworm PD model. Conclusions: This study provides a promising animal model for elucidating the pathogenesis of PD, as well as a relevant preliminary drug screening (e.g., LBP) and evaluation.

Metformin is a hypoglycemic agent used clinically in the treatment of type 2 diabetics. In addition, metformin is being investigated as a potential geroprotector. Here, we investigated the effects of metformin silkworm lifespan and the underlying molecular pathways involved. We found that metformin prolonged the lifespan of the male silkworm without reducing body weight, which suggests metformin can increase lifespan through remodeling of the animal's energy distribution strategy. Consistent with that idea, metformin reduced silk production and thus the energy devoted to that process. Metformin also increased fasting tolerance and levels of the antioxidant glutathione, and also activated an adenosine monophosphate-activated protein kinase-p53-forkhead box class O signaling pathway in silkworm. These results suggest that activity in this pathway may contribute to metformin-induced lifespan extension in silkworm by increasing stress resistance and antioxidative capacity while reducing energy output for silk product. The results also show that the silkworm is a potential useful animal model for evaluating the effects of small molecules with potential clinical utility.

The traditional Chinese medicine Astragalus polysaccharide (APS) has been widely used to improve glucose homeostasis and immunoregulator properties. In recent years, it has also been shown to extend the lifespan of Caenorhabditis elegans; however, the underlying molecular mechanisms are not fully understood. Here, our study shows that APS could significantly extend adult stage, mean, and maximum lifespan of the silkworm, Bombyx mori and increase body weight without affecting food intake and fecundity. Meanwhile, the activities of glutathione S-transferase and superoxide dismutase are significantly enhanced, and the reaction oxygen species content is reduced concomitantly. Moreover, the activity of lysozyme is increased dramatically. In addition, APS rescues the shortened lifespan by Bacillus thuringiensis infection in silkworm. Furthermore, the transcription of the crucial genes involved in endoplasmic reticulum stress is upregulated upon the endoplasmic reticulum stress stimulation. APS also significantly ameliorates endoplasmic reticulum stress in silkworm cell line and in vivo. Together, the results of this study indicate that APS can prolong the silkworm lifespan by mitigating endoplasmic reticulum stress. This study improves our understanding of the molecular mechanism of APS-induced lifespan extension and highlights the importance of the silkworm as an experimental animal for evaluating the effects and revealing the mechanisms in lifespan extension of traditional Chinese medicine.

Aging and lifespan study had been the intense subjects of biological science. By now, nematode (Caenorhabditis elegans) and fruit fly (Drosophila melanogaster) are the most widely used experimental invertebrates in aging and lifespan researches. Considering the complicated mechanism, utilization of more model organisms is indispensable for its evolutionary conservation and species specificity. Moreover, it is easier to make a breakthrough in the experimental animal with low cost, relatively integrated and differentiated physiological systems, and simple body composition which is more susceptible to exogenous regulation than mammals. The silkworm, Bombyx mori, has been regarding as a new choice for some aging and lifespan research, especially in longevity genes' function, signaling transduction and medicine efficacy evaluation study as its many features. Here, we discuss the objective conditions of this species as an invertebrate model for aging and lifespan research. Meanwhile, the major limitation reasons were also discussed for future work in research on aging and lifespan.