This supplement proposes new studies to advance the goals of the parent R01 grant ?Prebiotic Regulation of Longevity?. In our studies, we have discovered a pro-longevity compound, colanic acid (CA), produced and secreted from bacteria residing in the host, which regulates mitochondrial activities to exert its beneficial effects on the host. In the parent R01 grant, we proposed genetic and molecular studies in bacteria, Caenorhabditis elegans and mice to dissect the regulatory mechanisms underlying this novel longevity-promoting mechanism. In our recent studies, we also found that CA attenuates age-associated pathologies caused by toxic amyloid-b accumulation, and discovered a CA inducer, cephaloridine, that promotes the induction of CA from bacteria and lifespan extension in the host. Therefore, in this supplement, we propose to expand the parent award to add new studies on Alzheimer?s disease (AD). In the specific aim 1, we will determine the protective effect of CA and cephaloridine in C. elegans AD models; in the specific aim 2, we will determine the protective effect of cephaloridine in mouse AD models; in the specific aim 3, we will develop cephaloridine derivatives with enhanced CA induction activity. All the experiments are designed for the timeframe of one year. Successful accomplishment of these studies will significantly expand the scope and impact of the parent award by bridging aging biology, nutrition science and AD research. These studies will open a new avenue to apply nutraceutical approaches for the prevention and treatment of AD and will shed light on the extension and improvement of quality of life for AD patients in our current society and future generations.
Results from this supplement are important for public health as increased incidence of Alzheimer?s disease with age. Studies in this supplement will provide a novel prebiotic approach for the prevention and treatment of Alzheimer?s disease and develop new chemical compounds for targeting the microbiota-gut-brain axis to improve brain health.
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| Jiang, Xiqian; Wang, Lingfei; Carroll, Shaina L et al. (2018) Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox Biology Applications. Antioxid Redox Signal 29:518-540 |
| Lin, Chih-Chun J; Neve, Isaiah A A; Wang, Meng C (2018) Neuronal regulation of longevity by staying cool. Genes Dev 32:197-198 |
| Jiang, Xiqian; Zhang, Chengwei; Chen, Jianwei et al. (2018) Quantitative Real-Time Imaging of Glutathione with Sub-Cellular Resolution. Antioxid Redox Signal : |
| Han, Bing; Sivaramakrishnan, Priya; Lin, Chih-Chun J et al. (2017) Microbial Genetic Composition Tunes Host Longevity. Cell 169:1249-1262.e13 |
| Yu, Yong; Mutlu, Ayse Sena; Liu, Harrison et al. (2017) High-throughput screens using photo-highlighting discover BMP signaling in mitochondrial lipid oxidation. Nat Commun 8:865 |
| Chen, Jianwei; Jiang, Xiqian; Zhang, Chengwei et al. (2017) Reversible Reaction-Based Fluorescent Probe for Real-Time Imaging of Glutathione Dynamics in Mitochondria. ACS Sens 2:1257-1261 |
| Jiang, Xiqian; Chen, Jianwei; Baji?, Aleksandar et al. (2017) Quantitative real-time imaging of glutathione. Nat Commun 8:16087 |
| Lin, Chih-Chun Janet; Wang, Meng C (2017) Microbial metabolites regulate host lipid metabolism through NR5A-Hedgehog signalling. Nat Cell Biol 19:550-557 |
| Wang, Meng C (2017) Building multidisciplinary research. Mol Biol Cell 28:2905-2907 |
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