Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved..

Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and αSMA staining), inflammatory response (IL-1β, IL-6, and TNF-α), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:173

Enthalten in:

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 173(2024) vom: 27. März, Seite 116415

Sprache:

Englisch

Beteiligte Personen:

Nie, Lulin [VerfasserIn]
He, Kaiwu [VerfasserIn]
Qiu, Chaoming [VerfasserIn]
Li, Qing [VerfasserIn]
Xiong, Bocheng [VerfasserIn]
Gao, Chuanyue [VerfasserIn]
Zhang, Xiufen [VerfasserIn]
Jing, Mei [VerfasserIn]
Wu, Wei [VerfasserIn]
Liu, Jianjun [VerfasserIn]
Zhang, Gaoxiao [VerfasserIn]
Zhang, Zaijun [VerfasserIn]
Yang, Xifei [VerfasserIn]
Sun, Yewei [VerfasserIn]
Wang, Yuqiang [VerfasserIn]

Links:

Volltext

Themen:

AMP-Activated Protein Kinases
AMPK signaling
EC 2.7.11.31
Galactose
Journal Article
Mitochondrial function
Motor deficits
Muscle aging
Neuroprotective Agents
Pyrazines
Tetramethylpyrazine nitrone
Tetramethylpyrazine nitrone (TBN)
X2RN3Q8DNE

Anmerkungen:

Date Completed 27.03.2024

Date Revised 27.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.biopha.2024.116415

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369688961