Domestic researchers revealed that the starting point of the problem of muscle weakening as one ages is the 'brain.'
The National Research Foundation of Korea noted on the 13th that a research team led by Professor Kim Sang-ryong and Professor Lee Joon-young from Kyungpook National University, along with Dr. Nam Young-pyo, Dr. Kim Se-hwan, and Senior Researcher Kim Jae-gwang from the Korea Brain Research Institute, identified that the functional decline of the dopamine neural system located in the substantia nigra and striatum is one of the fundamental causes of the decrease in muscle mass due to aging, and that it is possible to suppress muscle atrophy based on this.
Deterioration of motor function and muscle atrophy due to aging drastically lowers the quality of life in old age. It has been confirmed that the 'substantia nigra-striatal dopamine neural system,' which is a key brain circuit for motor control, is highly sensitive to aging and closely linked to physical abilities; however, there have been almost no attempts to apply this to anti-aging research.
The research team believes that inducing anti-aging effects in the aging-sensitive substantia nigra-striatal dopamine neural system could solve the issues of decreased motor ability and muscle atrophy caused by aging.
First, the researchers confirmed that the expression of sirtuin 3 (SIRT3), one of the anti-aging factors in the substantia nigra of aged mouse models, decreases with aging. Sirtuin 3 is one of the proteins found in mammals, which plays roles in delaying aging and regulating energy metabolism.
When a gene that enhances the expression of sirtuin 3 is delivered into dopamine nerve cells, mitochondrial function, which plays a key role in energy production within cells, is activated, and the expression of the aging marker protein (p16INK4a) decreases.
In a mouse model with increased expression of sirtuin 3 in the substantia nigra, an evaluation of motor function showed that the decline in motor function was alleviated, and skeletal muscle mass was also maintained. Additionally, analysis of skeletal muscle tissue revealed that the neuromuscular junction, where nerves and muscles connect, was also protected in this mouse model.
Professor Kim Sang-ryong said, "This shows that the fundamental cause of the decline in physical strength and muscle atrophy that occurs in everyone as they age may be due to the decline in brain-motor nerve function related to aging," adding, "It is expected to provide a foundation for the future development of customized anti-aging therapies that protect the nervous system."
This research achievement was published in the international journal of biochemistry and molecular biology 'Signal Transduction and Targeted Therapy' on the 12th.
References
Signal Transduction and Targeted Therapy (2025), DOI: https://doi.org/10.1038/s41392-025-02234-7