1144
Received October 18, 2018
Accepted for publication October 20, 2018

“What we have here is a failure to communicate.” 
Cool Hand Luke

Communication between the brain and muscle plays a key 
role in maintaining the function of an individual. A classical 
example of this failure to communicate is after a stroke 
which leads to a failure of the brain to communicate with 
the periphery resulting in the muscle becoming flaccid. With 
aging there is a gradual decline in the communication between 
the central nervous system and skeletal muscle. This leads 
to a decrease in speed of movement, weakness, an increased 
tendency to fall and eventually a decline in function.

A number of studies have shown that deterioration in brain 
function leads to a decline in grip strength and walking speed. 
For example, older persons with the lowest MiniMental Status 
Examination score and poor verbal ability had lower grip 
strength (1). Ten percent variance in gait speed is due to the 
amyloid-beta burden in the brain together with the presence 
of the apolipoprotein E4 gene (2). A classical example of the 
brain-muscle communication decrease with aging is the decline 
in the ability of old persons with dementia or Parkinson’s 
disease to “dual task” (3). “Dual tasking” deficit is the inability 
to maintain walking speed while being asked to carry out a 
mental task. Both children up to 12 and older persons have 
a decrease in walking speed when asked to do an arithmetic 
problem.

With aging there is a decrease in axonal communication 
leading to a decline in the connection between the cortex 
and the spinal cord (4). The decline in dopamine receptors 
with aging results in slowed reaction times (5). With aging 
there is a decrease in motor unit numbers leading to fiber size 
heterogeneity and fiber grouping similar to the changes seen 
in amyotrophic lateral sclerosis and a loss of type 2 muscle 
fibers (6). When this is pronounced, it results in sarcopenia. In 
addition, the increase in adenosine (A1) inhibitory receptors 
over the adenosine 2A receptors results in decreased muscle 
force (7).

From Muscle to Brain

“Methinks that the moment my legs begin to move,
My thoughts begin to flow”

~Henry David Thoreau, 1851

Physical exercise increases hippocampal volume in older 
persons (8). In persons with mild cognitive impairment there 
is an increase in brain activation after 12 weeks of training (9). 
Exercise increases mental performance and function in older 
persons (10-13). Overall, exercise increases neurogenesis, 
neuronal maturation, angiogenesis, hippocampal volume and 
learning and memory in mice (14). Exercise directly increases 
BDNF, APP and BACE-1 in Alzheimer’s disease rat brain (15).

For muscle to produce these effects it produces a variety of 
myokines that have a direct effect on the brain (16). Among 
these myokines the ones that have been shown to have effects 
on the central nervous system include insulin-growth factor-1, 
brain derived nerve growth factor, cathepsin-B, fibroblast 
growth factor-1 and irisin (17). Irisin has been considered 
a major peptide communicator (18), but recently studies 
have suggested that the assays that have been used are very 
nonspecific (19, 20).

Another effect of muscle on the brain is to increase fatigue 
(21). Exercising muscle increases tryptophan and branched 
chain amino acids release in the blood leading to an increase 
in tryptophan in the brain (22, 23). In the brain tryptophan is 
converted into serotonin that inhibits neuronal activity leading 
to a sense of fatigue (24). Exercise also reverses depressive 
behaviors (25).

Cognitive Frailty

Cognitive frailty is defined as a person with reduced 
cognitive reserve associated with physical frailty (26, 27) 
(Figure 1). Persons with cognitive frailty have worse physical 
outcomes than persons who only have frailty (28-30).

Persons who have an increase in regional white matter 
burden (vascular disease) have increased balance and gait 
disorders, falls, urge incontinence, functional decline, and 
disability and worse executive function (31-33). Besides the 

EDITORIAL

BIDIRECTIONAL COMMUNICATION BETWEEN BRAIN AND MUSCLE  

J.E. MORLEY
Division of Geriatric Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. Corresponding author: John E. Morley, MB,BCh, Division of Geriatric Medicine, 

Saint Louis University School of Medicine, 1402 S. Grand Blvd., M238, St. Louis, MO 63104, Email: john.morley@health.slu.edu  

Key words: Brain communication, muscle, function.

© Serdi and Springer-Verlag International SAS, part of Springer Nature

J Nutr Health Aging. 2018;22(10):1144-1145

Published online November 26, 2018, http://dx.doi.org/10.1007/s12603-018-1141-2



THE JOURNAL OF NUTRITION, HEALTH & AGING©

J Nutr Health Aging
Volume 22, Number 10, 2018

1145

role of vascular disease producing cognitive frailty, another 
causative factor is inflammatory cytokines. Inflammatory 
cytokines are elevated in physical frailty (34). The cytokines 
can cross the blood brain barrier leading to impaired cognition 
(35).

Figure 1
Pathophysiology of Cognitive Frailty and Its Outcomes

Motoric Cognitive Risk Syndrome is similar to cognitive 
frailty (36). It is defined as an older person with slow gait and 
memory complaints, without dementia. Its pathophysiology 
is considered to be due to decreased gray matter volume and 
hippocampal volume together with an increase in white matter 
hyperintensities.

Conclusion

A failure to communicate between brain-muscle-brain plays 
a significant role in the aging process. This failure leads to 
frailty, sarcopenia, fatigue, depression and cognitive frailty 
(Figure 2).

.

Disclosures:  The authors declare there are no conflicts

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