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Exercise and the Brain/Nervous System Connection


As a consequence of our current lifestyle choices, including sedentary lifestyle, consumption of non-nutrient rich foods, not managing stress, our brain-body communication continually experiences a dangerous chronic positive energy balance (PPEB) – energy intake is greater than energy expenditure – that may lead to obesity, insulin resistance, the development of age-related diseases such as diabetes, cardiovascular disease, cancers, and neurodegenerative disorders and burdening our already broken healthcare system.

These current lifestyle choices can trigger epigenetics, modifying gene expression, thereby deceiving our evolutionary history encoded in our genes to includes periods of rest and digest with fight or flight. For optimal fitness, our genetics and cellular function needs to be challenged to stimulate the expression of “survival genes” which encode for proteins and enhance cells’ ability to withstand oxidative and metabolic stress. Thus, the concept of hormesis must be stimulated; in other words, “an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress”.

In the past 2 million years, humans are the only primates capable of sustained long distance running which may be due to the long spring-like calcaneus tendons in the legs and the plantar arch of the foot which acts as a spring returning up to 20% of energy generated during weight-loading phase of a running stride. Other adaptations that play a role in endurance running include long legs, and stride length, small feet with short toes, slow twitch muscle cells, large gluteus maximus muscle, structural modifications in the hips and shoulders generating a counter-balance force, sweat glands, reduced body hair and elongated body for heat dissipation, and mouth breathing.

Brain Connection:

The brain and its cognitive capabilities may also played an important role in endurance because of the required complex cognitive processes: the retention and recall of details, like topography, potential food sources, water sources, etc. of the surrounding land were required to effectively and efficiently acquire resources. And it is the nervous system that mediates the body’s movements, from milliseconds to years, that is mediated by nerve cell circuits within the cerebral cortex.

Besides exercises strengthening muscles and improving muscle tone, it is well-established that endurance exercise also strengthens brain cells, stimulate growth, and improve cognitive function. Neurotrophic factors are defined as growth factors that are secreted by tissue preventing cell death of the associated neuron, thus encouraging neuron survival. For example, running stimulates the production of brain-derived neurotrophic factors (BDNF) promoting the growth of dendrites, strengthening synapses and nerve cell generation from brain stem cells.

Age-related Exercise:

A study in young animals showed exercise induced superoxide and nitric oxide in muscle cells, and the stimulation of several transcription factors which induced the expression of antioxidant enzymes and protein chaperones. The proteins produced remained well beyond the exercise period such that stress induced during exercise resulted in long lasting resilience of muscle cells. This method of signaling from the effects of exercise on muscle cells is supported by data showing that treatment of humans with antioxidants vitamin E and C stop the ability of exercise to activate the protein PGC-1A and enhance insulin sensitivity in muscle cells. Oxidative stress in muscle cells trigger mitochondrial biogenesis mediated by PGC-1α regulator during exercise.

Unfortunately, adaptive response of muscle cells to exercise is compromised during the aging process, with no significant increase in protein chaperone and antioxidant enzymes. In addition, the combination of increased basal oxidative stress/damage and inflammation may prevent old muscle cells incapable of adapting to exercise. Since regular exercise during midlife and onwards can delay age-related muscle atrophy, it is probable that signaling pathways that induce the beneficial effects on muscle cells are well-maintained as a result of midlife exercises.

Regardless, an abundance of human studies have indicated that endurance exercises benefit both muscles and cardiovascular health even when initiated in the elderly who had relatively sedentary lifestyles in their midlife.

Neurotrophic Factors and the Brain:

During and post endurance exercise, there is extensive activation of signaling pathways in several different organ systems and nerve cells in the brain cells being highly responsive to exercise. The benefits of endurance exercise has been corroborated by both animal and human studies reinforcing that exercise induces neurotrophic factor expression thereby promoting structural and functional plasticity of neurons and their resistance to injury and disease. Aerobic exercise can elevate BDNF levels, increase hippocampus size and improve memory in the elderly. In running, BDNF expression is induced by synaptic activity-mediated activation of transcription factor CREB and energetic stress-mediated activation of transcription factor CREB. CREB is defined as a stress sensor it induces BDNF expression, and also the expression of multiple genes that encode proteins involved in the protection of neurons against oxidative stress.

Intercellular signaling pathways in the brain have also evolved in the adaptive response to exercise. This includes the expression of

  • Fibroblast growth factor 2 which is involved in protection of neurons against oxidative, metabolic and excitotoxic injury, promotes the growth of astrocytes to provide metabolic neuron support, and proliferation of neural progenitor cells.

  • VEGF which enhances angiogenesis in the hippocampus thereby increasing nutrients to brain cells.

With endurance exercise, energy reserves are utilized by both skeletal and cardiac muscles; but the energy supply must be maintained along the brain pathway because nerve cells require a constant supply of energy, otherwise it will become dysfunctional in the presence of hypoglycemia with low blood & oxygen supply. Thus, endurance training can enhance glucose availability to neurons.

BDNF is a crucial regulator of energy metabolism and mediator in adaptive responses of the brain and body to endurance exercise. Increased expression of BDNF may facilitate enhanced insulin sensitivity in response to endurance exercise and is consistent with studies showing increased BDNF levels in the brain reduce plasma glucose levels and mitigate diabetes in mice.

A recent study indicated that hypothalamic BDNF signaling can induce brown fat cell generation within white adipose via modulation of the autonomic nervous system of the white fat. It was also found that intermittent food deprivation reducing resting heart rate and blood pressure while improving cardiovascular adaptation to stress in rats by increasing parasympathetic tone and improving heart rate variability. This suggests that BDNF acts as a mediator on the heart and ultimately the role of BDNF as an integrator in brain-body interface and endurance of the body’s major systems involved in regulating neural, endocrine, and cardiovascular adaptation.

What Can Be Don? Start Moving:

Research has shown that these four types of exercise are important for optimal health:

  1. endurance

  2. strength

  3. balance

  4. flexibility

Engaging in one category of exercise improves your ability to perform the other types of exercises. ENDURANCE Endurance exercises, also known as aerobic exercise improve cardiovascular health (heart, lungs, circulatory system) by increasing breathing and heart rate thereby helping you perform everyday tasks and delay/prevent diseases such as diabetes, colon and breast cancers, heart disease, and others. To build endurance exercises should be performed for at least 150min of activity per week and makes you breath hard but you can still have a conversation. Avoid sitting for long periods of time.

Types of exercises include

  • brisk walking/jogging

  • yard work such as mowing/raking

  • dancing

  • swimming

  • biking

  • climbing stairs/hills

  • playing tennis/basketball

STRENGTH Strong muscles help keep you independent and provide ease of movement with everyday activities, such as sitting in a chair, climbing stairs, and carrying groceries. In addition, strong muscles support balance and prevent falls and fall-related injuries when your joints move effortlessly. Try using weights or resistance bands to help improve muscle strength. Start of light and progress with increasing weights/resistance when you feel comfortable to advance. Don’t forget to breath.

Exercises should be completed 2x per week. Exercises include

  • lifting weights

  • carrying groceries

  • gripping a tennis ball

  • overhead arm curl

  • arm curls

  • wall push-ups

  • lifting you body weight

  • using resistance bands

BALANCE Exercises focused on balance help prevent falls and prevent serious consequences. Lower body strength exercises will improve balance.

Exercises to improve balance include

  • tai chi

  • standing on one foot

  • heel-to-toe walk

  • balance walk

  • standing from a seated position

FLEXIBILITY Stretching improves flexibility and the slide-glide needed when reaching, bending, rotating the body when you are reaching into a cupboard, tying your shoes, or looking over your shoulder. Exercises include

  • back stretches

  • inner thigh stretches

  • ankle stretches

  • back of the leg stretches

For workout videos and examples of how to do some of the exercises listed below, visit NIA’s YouTube channel.

If you are unsure of the exercises to perform, seek help from a licensed professional such as a physiotherapist, yoga instructor, fitness trainer etc.


Mattson, Mark P. “Evolutionary aspects of human exercise--born to run purposefully.” Ageing research reviews vol. 11,3 (2012): 347-52. doi:10.1016/j.arr.2012.01.007

Neurotrophic factor definition & meaning. Merriam-Webster. Accessed March 12, 2022.

Four types of exercise can improve your health and physical ability. National Institute on Aging. Accessed March 12, 2022.


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