Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation

Wenhao Chen; Zile Shen; Wenxi Dong; Guowei Huang; Dingye Yu; Weizhe Chen; Xialin Yan; Zhen Yu

doi:10.1016/j.phymed.2024.155567

Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation

Phytomedicine. 2024 Mar 24:129:155567. doi: 10.1016/j.phymed.2024.155567. Online ahead of print.

Authors

Wenhao Chen¹, Zile Shen², Wenxi Dong², Guowei Huang¹, Dingye Yu³, Weizhe Chen², Xialin Yan⁴, Zhen Yu⁵

Affiliations

¹ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
² Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
³ Department of General Surgery, Huadong Hospital, Fudan University, Shanghai 200040, China.
⁴ Department of Colorectal Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: yanxialin2015@163.com.
⁵ Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: yuzhen@tongji.edu.cn.

PMID: 38579644
DOI: 10.1016/j.phymed.2024.155567

Abstract

Background: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia.

Purpose: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro.

Methods: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo.

Results: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca²⁺ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue.

Conclusion: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.

Keywords: Ca(2+) homeostasis; Mitochondria-associated membrane; Polygonatum sibiricum polysaccharide; Senescence.