The budding yeast has been used as a model organism for the basic mechanism of aging, which provides useful assay systems for measuring both replicative and chronological lifespans. In the course of our screening program for substances that extend replicative lifespan, cucurbitacin B (CuB) was found as a hit compound from a compound library, which contains cerebrosides, phenols, sesquiterpenoid, triterpenoids, and sterols isolated from natural products by our research group. Importantly, it prolonged not only the replicative lifespan but also the chronological lifespan in yeast. CuB increased gene expression, suggesting that CuB induces autophagy. Indeed, the GFP signal generated from the cleavage of GFP-Atg8, which is a signature of autophagy, was increased upon CuB treatment. On the other hand, CuB failed to increase the chronological lifespans when either or , essential autophagy genes, was deleted, indicating that the lifespan extension by CuB depends on autophagy induction. Furthermore, CuB significantly increased superoxide dismutase (Sod) activity and the survival rate of yeast under oxidative stress, while it decreased the amount of reactive oxygen species (ROS) and malondialdehyde (MDA) production, indicating that CuB has activity to antagonize oxidative stress. Additionally, CuB did not affect replicative lifespans of , , , and mutants with the K6001 background, indicating that aging-related genes including , , , and participate in the antiaging effect of CuB. These results suggest that CuB exerts antiaging activity by regulating autophagy, ROS, antioxidative ability, and aging-related genes. Finally, we discuss the possible intracellular targets of CuB based on the phenotypic comparison between the CuB and global gene deletion databases.
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http://dx.doi.org/10.1155/2019/4517091 | DOI Listing |
Sci Rep
January 2025
Wildlife Institute of India, Dehradun, 248001, Uttarakhand, India.
Intra-specific interactions among top carnivores are among the most intriguing behavioural aspects and essential components of population dynamics. Static interactions pertain to space use, while dynamic interactions involve spatio-temporal patterns influenced by social structure, distribution, mate selection, and density. Previous studies have focused on static interactions, successfully estimating spatial overlap but leading to a knowledge gap of dynamic interaction to be able to compute attraction and avoidance on similar spatio-temporal scales.
View Article and Find Full Text PDFBlood Adv
January 2025
KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Allosteric regulation of ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type-1 motif, member 13) activity involves an interaction between its Spacer (S) and CUB1-2 domains to keep the enzyme in a closed, latent conformation. Monoclonal antibodies (mAb) uncouple the S-CUB interaction to open the ADAMTS13 conformation and thereby disrupt the global enzyme latency. The molecular mechanism behind this mAb-induced allostery remains poorly understood.
View Article and Find Full Text PDFAnimals (Basel)
December 2024
Sichuan Key Laboratory of Conservation Biology on Endangered Wildlife, Chengdu Research Base of Giant Panda Breeding, Chengdu 610081, China.
The giant panda () is one of the animals with the largest body weight differences between its birth and adult stages, where the newborn cub is 0.1% the size of its mother. The rapid growth of panda cubs has been reported previously, but little is known about the growth pattern of their entire lifetime.
View Article and Find Full Text PDFFront Genet
December 2024
Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Introduction: We investigated the relationship between systematic regulators of inflammation and the risk of age-related macular degeneration (AMD), both wet and dry forms, by using bidirectional, two-sample Mendelian randomization (MR).
Methods: We performed bidirectional two-sample Mendelian randomization analysis using genome-wide study (GWAS) data for 91 plasma proteins from 14,824 individuals of European descent across 11 study groups. Next, we utilized data from the FinnGen consortium to study AMD using the inverse- variance-weighted approach for Mendelian randomization.
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