Muscle-Targeted Nanocomposite Therapy Alleviates Age-Related Sarcopenia via Antioxidant and Metabolic Reprogramming.

Area of Science:

• Gerontology
• Biomedical Engineering
• Molecular Biology

Background:

• Sarcopenia is a progressive skeletal muscle disorder characterized by loss of mass and function.
• Limited therapeutic options exist for sarcopenia, posing societal challenges.
• Mitochondrial dysfunction and oxidative stress are identified as key drivers of sarcopenia.

Purpose of the Study:

• To engineer a muscle-targeted nanocomposite for treating sarcopenia.
• To address the pathophysiology of sarcopenia by combining mitochondrial restoration and antioxidant properties.
• To validate the efficacy and safety of the developed nanocomposite in preclinical models.

Main Methods:

• Integrated bioinformatics and clinical validation to identify sarcopenia drivers.
• Engineering of a muscle-targeted nanocomposite (BP-PEG-MOTS-c, BM) combining MOTS-c and black phosphorus nanosheets (BP).
• In vitro and in vivo studies using cellular and murine models of age-related sarcopenia, including RNA-seq for mechanistic profiling and toxicity assays.

Main Results:

• BM treatment alleviated muscle dysfunction and loss in sarcopenia models.
• BM normalized mitochondrial function and reduced lipid peroxidation.
• RNA-seq revealed BM activates PI3K/AKT/Nrf2 and suppresses ROS/p38 MAPK signaling, promoting antioxidant responses and mitochondrial homeostasis.
• The nanocomposite demonstrated superior biocompatibility compared to conventional delivery systems.

Conclusions:

• The engineered nanocomposite (BM) is a promising mitochondrial redox modulator for sarcopenia.
• BM effectively targets key pathological mechanisms of sarcopenia, including mitochondrial dysfunction and oxidative stress.
• BM holds translational potential for treating sarcopenia and other age-associated pathologies.