The Still Largely Unmapped Neuroprotective Mechanisms of Exercise
Regular moderate exercise delays the onset of neurodegeneration in late life. Since exercise produces sweeping changes throughout the body and the operation of cellular metabolism. It is easy enough to look at what is known of the connections to brain aging, such as a reduction in the chronic inflammation associated with aging, or upregulation of beneficial metabolites leading to an increase in BDNF expression and consequent neurogenesis, and say that these are the most important factors. But one suspects that any number of other relevant mechanisms may remain to be discovered and characterized, and since researchers don't have a good grasp on the relative importance of the known mechanisms, those unknown mechanisms could well account for a sizable fraction of the outcome.
Regardless, the difference in late life health between highly active hunter-gatherer populations and largely inactive populations in wealthier regions of the world is sizable. This is particularly true for cardiovascular disease, but also applies to much of the panoply of common conditions that afflict older people. Degree of life-long exercise is likely a primary contributing factor in that difference. Given that we know that exercise is one of the safest forms of intervention, not to mention one of the cheapest, it seems self-sabotaging not to undertake more of it.
New insights into how exercise protects against neurodegenerative diseases
Accumulating evidence finds that exercise can improve brain function and delay or prevent the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's disease. While the underlying mechanisms remain unclear, recent research suggests that exercise-induced activation of peripheral systems such as muscle, gut, liver, and adipose tissue may affect neural plasticity. Cathepsin B (CTSB), a myokine, and brain-derived neurotrophic factor (BNDF) have been found to possess robust neuroprotective effects.
In a new study, investigators looked at whether increasing aerobic exercise intensity would increase the amount of CTSB and BDNF circulating in the blood. Sixteen young healthy subjects completed treadmill-based aerobic exercise at maximum capacity and then at 40%, 60%, and 80% of capacity. Circulating CTSB and BDNF were measured in blood samples taken after each bout of exercise, and CTSB protein, BDNF protein, and mRNA expression were measured in skeletal muscle tissue. Researchers found that high intensity exercise elevates circulating CTSB in young adults immediately after exercise, and that skeletal muscle tissue expresses both message and protein of CTSB and BDNF.
Further, new review articles cover interorgan crosstalk between muscle, liver, adipose tissue, the gut microbiome, and the brain. While it is well known that exercise protects the central nervous system, it has only recently been found to depend on the endocrine capacity of skeletal muscle. Researchers highlight the impact of myokines, metabolites, and other unconventional factors that mediate effects of muscle-brain and muscle-retina communication on neurogenesis, neurotransmitter synthesis, proteostasis, mood, sleep, cognitive function and feeding behavior following exercise.
They also raise the possibility that detrimental myokines resulting from inactivity and muscle disease states could become a novel focus for therapeutic intervention. "We propose that tailoring muscle-to-central nervous system signaling by modulating myokines and metabolites may combat age-related neurodegeneration and brain diseases that are influenced by system signals."