The number of elderly people (aged 65 and older) in the U.S. will be more than doubled, from 40.3 million in 2010 to 88.5 million in 2050. This rapid growth of the older population dramatically increases the incidence of chronic and degenerative diseases, and presents a grand challenge for public health. To tackle this challenge, our research aims to identify bioactive nutrient compounds that promote organismal longevity and fitness through modulating microbiota-host interactions, and to further characterize their underlying regulatory mechanisms. The microbiota is a collection of diverse species of microorganisms that reside in the host, and its homeostasis is strongly associated with host health and is tightly regulated by both dietary and genetic factors. Diet-driven microbiota compositional changes have been linked to health improvement among the elderly, however identification and validation of specific longevity-promoting bioactive dietary factors remain technically challenging in mammalian systems. During our preliminary studies in Caenorhabditis elegans, we identified a longevity-promoting polysaccharide, colanic acid (CA), which is secreted from bacteria and functions as a prebiotic to improve host mitochondrial dynamics. Our studies further revealed that CA promotes longevity in evolutionarily distant host organisms and is effective in diverse microbial environments. These studies suggest CA as a novel bioactive nutrient compound to improve microbiota homeostasis and to promote host metabolic health and fitness. This proposal seeks to dissect the prebiotic function of CA in the regulation of host longevity through the following specific aims: 1) Elucidate CA-mediated microbial factors that regulate host longevity; 2) Reveal the molecular mechanisms by which CA improves host longevity. 3) Assess the conserved role of CA in promoting host health and longevity in mammals. In these studies, we will apply multidisciplinary approaches and take advantages of powerful prokaryotic, invertebrate and vertebrate model systems. We have established unique collaborations with scientists in diverse areas. Successful accomplishment of the proposed studies will provide a new strategy of prebiotic therapies to improve the quality of later life, an will have significant impacts on research in the fields of nutritional science and aging biology.

Public Health Relevance

Results from this study are important for public health. Improvement of healthy aging in the elderly represents a big challenge for public health. This study will provide insight into prebiotic therapies as promising new strategies to promote health and longevity.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT009050-04
Application #
9689921
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wang, Yisong
Project Start
2016-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Han, Bing; Sivaramakrishnan, Priya; Lin, Chih-Chun J et al. (2018) Microbial Genetic Composition Tunes Host Longevity. Cell 173:1058
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 :
Wang, Meng C (2017) Building multidisciplinary research. Mol Biol Cell 28:2905-2907
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

Showing the most recent 10 out of 11 publications