Fight Aging!

BDNF levels decline with age. Much of the focus on BDNF has been its role in neurogenesis in the brain. Interventions such as exercise and reversing (or compensating for) the aging of the gut microbiome can boost BDNF levels and cognitive function in animal studies. For a different view on the relevance of BDNF, researchers here report on their investigations of the role of BDNF in muscle tissue, finding that it can upregulate the mitochondrial quality control mechanism of mitophagy, improving muscle function. They also note that obesity can harm muscle tissue function by reducing BDNF levels and thereby causing a loss of mitochondrial function. This work is perhaps a good reason to pay more attention to some of the known ways to upregulate BDNF as a basis for therapies.

A decline in metabolism and endurance of skeletal muscle is commonly observed in obese patients, but the underlying mechanism is not well-understood. Researchers developed a special obesified mouse model by removing the gene of brain-derived neurotrophic factor (BDNF) exclusively in their skeletal muscle. BDNF is originally identified as an important growth factor for maintaining the survival and activities of neurons. Recent studies have proposed that BDNF is also a muscle-secreted protein (i.e., myokine), but its physiological significance is unknown.

Researchers found that obesity reduced the amount of BDNF in the skeletal muscle of mice. They also observed that the mice without BDNF in their muscle, called 'MBKO' (Muscle-specific BDNF Knockout), gained more body weight and developed worse insulin resistance when the animals were fed with a high-fat diet. In addition, the research team found that MBKO mice have less energy expenditure than their control cohort. The research team further demonstrated that the mitochondria in the muscle of MBKO mice were unable to recycle, leading to the accumulation of damaged mitochondria in the tissues.

Researchers also utilized cultured cell models to pinpoint the molecular mechanism for the defective mitochondrial turnover in BDNF-deficient muscle cells. They found that muscle-secreted BDNF used AMP-activated protein kinase, the well-known energy sensor in cells, to trigger the Parkin/PINK1 pathway for inducing mitophagy (a highly regulated mechanism to recycle the materials in cells in response to various challenges) in skeletal muscle. To extend these findings to therapeutic application, the research team further tested if restoring the BDNF signaling in muscle would rescue the obesity-induced mitochondrial damage. They fed the obese mice with 7,8-dihydroxyflavone, a natural bioavailable BDNF mimetic in plants currently used in the clinical trials of Alzheimer's disease, and found that obesity-induced mitochondrial dysfunction was alleviated.

Link: https://www.hku.hk/press/press-releases/detail/23625.html