Dietary neoagarotetraose extends lifespan and impedes brain aging in mice via regulation of microbiota-gut-brain axis

Tao Li; Shaoqing Yang; Xiaoyan Liu; Yanxiao Li; Zhenglong Gu; Zhengqiang Jiang

doi:10.1016/j.jare.2023.04.014

Dietary neoagarotetraose extends lifespan and impedes brain aging in mice via regulation of microbiota-gut-brain axis

J Adv Res. 2023 Oct:52:119-134. doi: 10.1016/j.jare.2023.04.014. Epub 2023 Apr 20.

Authors

Tao Li¹, Shaoqing Yang¹, Xiaoyan Liu¹, Yanxiao Li², Zhenglong Gu³, Zhengqiang Jiang⁴

Affiliations

¹ Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
² Department of Nutrition and Health, College of Engineering, China Agricultural University, Beijing, China.
³ Division of Nutritional Sciences, Cornell University, NY, USA; Greater Bay Area Institute of Precision Medicine (Guangzhou), Nansha District, Guangzhou 511400, China; Institute of Life Sciences, Fudan University, Shanghai 200433, China. Electronic address: zg27@cornell.edu.
⁴ Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China. Electronic address: zhqjiang@cau.edu.cn.

Abstract

Introduction: Dietary oligosaccharides can impact the gut microbiota and confer tremendous health benefits.

Objectives: The aim of this study was to determine the impact of a novel functional oligosaccharide, neoagarotetraose (NAT), on aging in mice.

Methods: 8-month-old C57BL/6J mice as the natural aging mice model were orally administered with NAT for 12 months. The preventive effect of NAT in Alzheimer's disease (AD) mice was further evaluated. Aging related indicators, neuropathology, gut microbiota and short-chain fatty acids (SCFAs) in cecal contents were analyzed.

Results: NAT treatment extended the lifespan of these mice by up to 33.3 %. Furthermore, these mice showed the improved aging characteristics and decreased injuries in cerebral neurons. Dietary NAT significantly delayed DNA damage in the brain, and inhibited reduction of tight junction protein in the colon. A significant increase at gut bacterial genus level (such as Lactobacillus, Butyricimonas, and Akkermansia) accompanied by increasing concentrations of SCFAs in cecal contents was observed after NAT treatment. Functional profiling of gut microbiota composition indicated that NAT treatment regulated the glucolipid and bile acid-related metabolic pathways. Interestingly, NAT treatment ameliorated cognitive impairment, attenuated amyloid-β (Aβ) and Tau pathology, and regulated the gut microbiota composition and SCFAs receptor-related pathway of Alzheimer's disease (AD) mice.

Conclusion: NAT mitigated age-associated cerebral injury in mice through gut-brain axis. The findings provide novel evidence for the effect of NAT on anti-aging, and highlight the potential application of NAT as an effective intervention against age-related diseases.

Keywords: Alzheimer’s disease; Gut microbiota; Longevity; Neoagarotetraose; Neuronal injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging
Alzheimer Disease* / drug therapy
Alzheimer Disease* / metabolism
Alzheimer Disease* / microbiology
Animals
Brain / metabolism
Brain / pathology
Brain-Gut Axis*
Longevity
Mice
Mice, Inbred C57BL

Substances

neoagarotetraose