Mairin Slows Muscle Loss by Blocking Fibrosis Through Key Cellular Pathways

Jim Crocker
20th August, 2024

Mairin Slows Muscle Loss by Blocking Fibrosis Through Key Cellular Pathways

Image Source: Natural Science News, 2024

Key Findings

  • Researchers from Chengdu University of Traditional Chinese Medicine found that mairin, a compound in Astragalus membranaceus, can combat age-related muscle loss (sarcopenia)
  • Mairin was shown to prevent muscle fibrosis and atrophy in aging mice, improving muscle mass and strength
  • The compound works by activating the AMPK pathway, which reduces fibrotic signals and promotes muscle regeneration
Sarcopenia, the age-related loss of muscle mass and function, has become a significant health concern among the elderly. This condition leads to physical disabilities and increased mortality. Recent research from Chengdu University of Traditional Chinese Medicine has investigated the potential of mairin, a compound found in Astragalus membranaceus, to combat sarcopenia by targeting fibro-adipogenic progenitors (FAPs)[1]. FAPs are cells that have the ability to differentiate into adipocytes (fat cells) and fibroblasts (cells that generate fibrous tissue). These progenitors are crucial in regulating skeletal muscle development and are implicated in the progression of sarcopenia due to their role in muscle fibrosis and fat infiltration[2]. The study aimed to determine whether mairin could inhibit the fibrotic activity of FAPs and thereby mitigate sarcopenia. In the study, senescence-accelerated mouse-prone 8 (SAMP8) mice, a model known for age-related muscle and cognitive decline[3], were administered mairin orally at doses of 30 mg/kg/day or 60 mg/kg/day. Aging in these mice resulted in significant weight loss, reduced skeletal muscle mass, decreased strength and function, and increased muscle atrophy and fibrosis. However, mairin administration effectively inhibited these age-related physiological declines. Further in vitro experiments demonstrated that mairin at concentrations of 20 μM or 40 μM enhanced the proliferation of FAPs while inhibiting their differentiation into fibroblasts. This suggests that mairin can promote muscle regeneration by preventing the fibrotic conversion of FAPs. Mechanistically, the study found that mairin exerts its anti-fibrotic effects via the AMP-activated protein kinase (AMPK)-transforming growth factor beta (TGF-β)-SMAD signaling pathway. AMPK is a key energy sensor in cells that regulates various metabolic processes, including mitochondrial biogenesis and autophagy[4]. The study showed that mairin increased the phosphorylation of AMPKα, which in turn reduced the levels of TGF-β and phosphorylated-SMAD2/3, proteins involved in promoting fibrosis. This finding aligns with previous studies that have highlighted the importance of AMPK in maintaining muscle health and preventing metabolic disorders[4]. By activating AMPK, mairin appears to counteract the fibrogenic signals mediated by TGF-β and SMAD proteins, thereby reducing muscle fibrosis and improving muscle function. Additionally, the study explored potential target genes of mairin through mRNA sequencing, providing further insight into the molecular mechanisms by which mairin may exert its effects. These findings suggest that mairin could be a promising therapeutic agent for treating sarcopenia by modulating the AMPK/TGF-β/SMAD pathway to prevent FAP-mediated fibrosis. In summary, this research from Chengdu University of Traditional Chinese Medicine provides compelling evidence that mairin can ameliorate sarcopenia by targeting the fibrosis of FAPs through the AMPK/TGF-β/SMAD axis. This study not only expands our understanding of the cellular mechanisms underlying sarcopenia but also offers a potential new avenue for therapeutic intervention in age-related muscle degeneration.

MedicineHealthBiochem

References

Main Study

1) Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-β-SMAD axis.

Published 17th August, 2024

https://doi.org/10.1016/j.gene.2024.148873

Related Studies

2) Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention.

https://doi.org/10.1016/j.mam.2016.04.006

3) Targeting Multiple Mitochondrial Processes by a Metabolic Modulator Prevents Sarcopenia and Cognitive Decline in SAMP8 Mice.

https://doi.org/10.3389/fphar.2020.01171

4) Emerging Role of cAMP/AMPK Signaling.

https://doi.org/10.3390/cells11020308


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