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Topical Area: Aging and Chronic Disease

Aging and Chronic Disease (Poster Session)

(P23-016-23) Betaine Delaying Muscle Loss by Attenuating Aging-Related Suppression of Autophagy via Mettl21c/VCP Axi

Monday, July 24, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 16

    Presenting Author(s)

  • SC

    Si Chen, MD

    Post doctor
    Sun Yat-sen University
    Guangzhou, Guangdong, China (People's Republic)

    • Co-Author(s)

  • HZ

    Huilian Zhu, PhD

    Professor
    Sun Yat-sen University
    Guangzhou, Guangdong, China (People's Republic)

Disclosure(s):
Si Chen, MD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Aging-related suppression of autophagy pose threat to the muscle loss and may lead to sarcopenia. Our previous study indicated betaine could delay muscle loss. This study aims to investigate whether betaine delays muscle loss by attenuating aging-related suppression of autophagy.

Methods: Male C57BL/6J mice (15-mon) were randomized into control group (Con, n=5) or betaine intervention group (Bet, n=5) for 12 weeks intervention. Young mice (2-mon) were raised in parallel (You, n=5). After intervention, RNA Sequencing was performed to screen the autophagy-regulating genes. C2C12 cells were used to further explore the mechanism. Muscle mass, strength and function were assessed by dual-energy X-ray absorptiometer, grasp meters and rotarod tests. RT-PCR and western blotting (WB) were applied to evaluate the expressions of autophagy markers. Electronic and confocal microscope were performed to assess the flux of autophagy in C2C12 cells. MGG staining was conducted to assess C2C12 differentia. ATP production and VCP assembly capability were also evaluated.

Results: During aging process, the expression of autophagy markers Atg5, Atg7, LC3-II, Becline or p62 decreased and accompanied with decline of muscle mass, strength and function. Betaine attenuated expressions decline of autophagy markers and delayed muscle loss. RNA-Seq revealed a S-adenosyl-L-methionine(SAM)-dependent autophagy-regulating methyltransferase, Mettl21c, was highly expressed in You and Bet group. So Mettl21c was knocked down in C2C12 cells under methionine deprived condition for further study. By elevating SAM concentration, Betaine increased the ATP production to promote assembly of Mettl21c down-stream effector VCP. WB, EM, confocal microscope and MGG staining results collectively shown betaine could increase expression of autophagy markers, activate autophagy flux and promote differentia in C2C12 cells via Mettl21c/VCP axi.

Conclusions: Betaine maintains muscle mass, strength and function by attenuating aging-related suppression of autophagy via Mettl21c/VCP axi.

Funding Sources: The China Postdoctoral Science Foundation (2022M713556); Natural Science Foundation of China (82204020); Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515110848); Natural Science Foundation of China (81773415).