Lycopene alleviates age-related cognitive deficit via activating liver-brain fibroblast growth factor-21 signalling.

Jia Wang, Lu Li, Li Li, Yuqi Shen, Fubin Qiu

Nutritional and Food Sciences Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: [email protected] and Food Sciences Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes' support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases.

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Research summary

The paper investigates the role of lycopene in alleviating age-related cognitive deficits through the activation of liver-brain FGF21 signaling, which suggests a potential mechanism linking nutrition to cognitive health in aging. This addresses a significant aspect of aging by exploring a nutritional intervention that may influence cognitive decline, thus contributing to the understanding of aging processes. However, while the findings are solid, they appear to be an incremental advance rather than a major breakthrough, limiting the overall impact.

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