Electrical Stimulation as a Basis for Some Forms of Compensatory Therapy for Age-Related Degeneration

Functional electrical stimulation has been used as the basis for therapies and prosthetics in cases of paralysis. In theory it can help slow degeneration of paralyzed limbs by exercising muscles, or in some lesser cases bypass damaged nerves sufficiently well to allow very limited function of otherwise paralyzed muscles. As prosthetic systems become more sophisticated, "limited function" increases in scope: consider the proof of concept from last year in which a paraplegic with spinal cord injury walked a few steps. This is still a long way from robust methods of bypassing damaged nerves, however. It is most likely that progress in regenerative medicine will enable repair of even very severe nerve damage before artificial nerve bypasses arrive at the point of enabling paraplegic patients to use their paralyzed limbs in a natural way.

Elsewhere, electrical stimulation of various sorts is used in a variety of therapies for a variety of conditions, and has been for some time - though the evidence for benefits and understanding of mechanisms involved is lacking in many cases. Looking forward to the future, some research groups are exploring the role of electric fields and signals in tissue growth, in regeneration, and in related uses in tissue engineering, as well as potentially providing a basis for selectively disabling cancer cells. But for today I'll point out a few recent research articles that focus firstly on whether or not electrical stimulation of muscles can be of use as a compensatory treatment for age-related muscle wasting, and secondly on electrical stimulation of the brain as a way to increase neuroplasticity - again a way to compensate in part for losses that occur due to aging. As is frequently the case in research, these are not approaches that address any of the root causes of degeneration, but rather try to add more capacity or resilience to impacted tissues. This will always be an inferior approach, capable of producing only lesser benefits, but the cost-benefit analysis for undertaking the work may still be favorable in many cases.

Brain Boost: ONR Global Sponsors Research to Improve Memory through Electricity

Researchers have significantly boosted the memory and mental performance of laboratory mice through electrical stimulation. The study involved the use of Transcranial Direct Current Stimulation, or tDCS, on the mice. A noninvasive technique for brain stimulation, tDCS is applied using two small electrodes placed on the scalp, delivering short bursts of extremely low-intensity electrical currents. "We already have promising results in animal models of Alzheimer's disease. In the near future, we will continue this research and extend analyses of tDCS to other brain areas and functions."

After exposing the mice to single 20-minute tDCS sessions, the researchers saw signs of improved memory and brain plasticity (the ability to form new connections between neurons when learning new information), which lasted at least a week. This intellectual boost was demonstrated by the enhanced performance of the mice during tests requiring them to navigate a water maze and distinguish between known and unknown objects. Although tDCS has been used for years to treat patients suffering from conditions such as stroke, depression and bipolar disorder, there are few studies supporting a direct link between tDCS and improved plasticity. More important, the researchers identified the actual molecular trigger behind the bolstered memory and plasticity - increased production of brain-derived neurotrophic factor (BDNF), a protein essential to brain growth. BDNF is synthesized naturally by neurons and is crucial to neuronal development and specialization.

Biology of Muscle Atrophy and of its Recovery by FES in Aging and Mobility Impairments: Roots and By-Products

We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers.

In extreme examples of muscle degeneration accompanying nerve disconnection, we have gathered data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation (FES) in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it should be possible to defer the muscle decline that occurs in aging people and in those who have become unable to participate in physical activities. Thus, FES should be considered for use in rehabilitation centers, nursing facilities and in critical care units when patients are completely inactive even for short periods of time.

Molecular and Cellular Mechanisms of Muscle Aging and Sarcopenia and Effects of Electrical Stimulation in Seniors

One of the problems associated with aging is that some people cannot move because of pathological conditions like pain, osteoarthritis and so on. Is there an alternative approach instead of physical exercise for these people? Researchers designed a specific way of analyzing electrical stimulation to address the question: can electrical stimulation mimic the effect of physical exercise? In particular, a stimulator for neuromuscular electrical stimulation was designed, especially suiting the requirements of elderly people with diminished fine motor skill. What was demonstrated is that electrical stimulation did improve muscle performance. The increase in muscle strength was associated with an increase of muscle fibers and most importantly with an increase of fast fibers, which are related to the power of the skeletal muscle. We asked: what is the mechanism associated with this increase of muscle strength and increase in muscle mass?

Since IGF-1 is one of the factors that are activated during physical exercise, we verified whether electrical stimulation was able to induce an increase in IGF-1 expression. At first, we analyzed the expression of the different types (isoforms) of IGF-1. All of them were up regulated after electrical stimulation. Then we analyze some downstream pathways activated by IGF-1. We demonstrated that electrical stimulation stimulates not only anabolic pathways, but negatively modulates muscle catabolism. Another component that we analyze is collagen expression. There is remodeling, not only during physical exercise but also in electrical stimulation of extracellular matrix (ECM). Of note histology did not reveal any accumulation of fibrotic tissue in electrical stimulated muscles. To further support the morphological evidences, we analyzed one of the important controllers of fibrosis, namely miR29. The electrical stimulation regulates miR29, which might block the accumulation of fibrosis. We then analyzed the number of satellite cells that can be activated by electrical stimulation. We wanted to verify whether electrical stimulation, similarly to exercise, can increase the activity of these cells. Electrical stimulation indeed increased the number of satellite cells.

In conclusion, what we demonstrated is that electrical stimulation, which can be applied to people that cannot carry out normal physical activity, modulates similar factors associated with physical exercise. All of these data might help to design therapeutic strategies to counteract muscle atrophy associated with aging.

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