When we practice a sporting activity, our muscles produce small molecules that are still little known: myokines. These substances are hormones capable of activating key functions within cells throughout our body. Certain myokines have documented anti-aging effects.
What Are Myokines?
Regular sports practice has multiple benefits on our health, reducing the risk of developing chronic diseases or their intensity, and mortality in general. The biological mechanisms allowing these effects have long been partially understood. Today research indicates a very important role for myokines in mediating these effects. Myokines are small proteins secreted by muscle fibers when they contract. They act on the muscle itself (autocrine action) and the tissues surrounding it (paracrine action), they are also released into the blood circulation. They thus exert effects on more distant organs such as the liver, kidneys, brain, bones, intestine, etc. The muscle can thus be described as a secretory organ due to this hormonal action.
A Very Large Number Of Myokines
The term myokine was first introduced in 2003 by a Swedish researcher, Bengt Saltin. Until this point in time, more than 650 myokines have been recognized. Their role remains poorly understood: the specific functions of only 5% of them have been characterized. The most studied myokines are interleukins 6, 8, 10, 13, 15, and 18, as well as muscle, irisin, fibroblast growth factor 21 (FGF21), myostatin, myonectin, and apelin. They could have therapeutic applications in the context of metabolic disorders because their deregulation in the event of a sedentary lifestyle is conducive to the occurrence of obesity and type 2 diabetes.
Promising Anti-Aging Effects
The field of anti-aging medicine is also closely interested in these compounds. Indeed, the secretion of most myokines diminishes over the years, which could contribute to the aging of the body. For example :
- The length of the end of chromosomes, generally considered a good marker of biological age, is for example correlated with the level of irisin.
- Interleukin 15 appears crucial against skin aging. Administration of IL-15 to aged mice, like physical exercise, improves the collagen content of the epidermis and dermis.
Anti-Aging Effect On Muscles
As we age, muscle mass and strength decrease. When the situation becomes critical, we speak of sarcopenia. A study involving French researchers from INSERM has highlighted the key role of one of the myokines, apelin, in this phenomenon which represents a factor of fragility for the elderly.
Decrease In Apelin With Age
If practicing a sporting activity raises the blood concentration of apelin, the mechanism becomes blunted with age, as the researchers have shown. They first analyzed the blood concentration of apelin in mice at different stages of their life: at the age of 3, 12, and 24 months. The results highlighted a progressive decline as the animals aged. This drop in the blood level of apelin is associated with a rarefaction of the compound itself, and of its receptors, at the muscular level.
When the young mice’s muscles were stimulated to imitate physical activity, they produced a higher amount of apelin compared to what was observed in their older littermates. The team then wanted to check whether these results could be transposed to humans. To do this, they used muscle cell cultures from elderly (68 to 83 years old) and younger (16 to 27 years old) donors. Here again, the loss of apelin content during aging was highlighted, as well as the decline in the reactivity of muscle cells to produce this compound.
Anti-Catabolizing Effect Of Apelin
The researchers then looked at how the muscular system of animals deprived of the action of apelin evolved during aging. To do this, they used a mouse strain deficient in apelin or its receptors. In both cases, the result is the same: the body cannot benefit from the effects of the compound. They found the muscles of these animals deteriorated much earlier than those of their peers.
Apelin Rejuvenates Muscles
To demonstrate indisputably the role of apelin as a source of muscle rejuvenation, a final step was undertaken: the administration of this compound to aged animals. The approach was able to reverse sarcopenia, leading to a significant increase in muscle mass and the proportion of large-diameter fibers. Several mechanisms leading to this restoration of muscle integrity have been identified.Â
Apelin stimulated the formation of new mitochondria, the energy-producing units, and promoted protein synthesis within sarcopenic muscle fibers. Additionally, it increased the amount of muscle stem cells and their ability to proliferate and fuse to regenerate damaged muscles. Previous work has shown that the anti-aging effects of apelin extend beyond the muscular sphere. Its administration slowed down the overall aging of the mouse organism and prolonged their life expectancy.
Cooperation Of Myokines Against Sarcopenia
Other myokines exert favorable effects in preventing muscle aging :
- Irisin also induces muscle regeneration by activating stem cells.
- FGF21 prevents muscle atrophy caused by inflammatory conditions, often present in older people.
- Meteorin-like promotes the formation of new muscle tissue.
- IGF-1 is an essential myokine for muscle growth and regeneration. Low levels of this myokine are associated with an increased risk of sarcopenia.
By increasing the secretion of these myokines, physical exercise in the elderly can thus contribute to the maintenance of muscle function, reducing the risk of falls and fractures which often lead to loss of autonomy.
Anti-Aging Effect On The Brain
Myokines could also represent a means of slowing down brain aging and maintaining mental abilities over the years.
Preventing The Decline Of Mental Faculties
Sport has favorable effects on brain health and cognitive functions, particularly in the elderly population. A meta-analysis demonstrated the central role of physical activity in combating age-related cognitive decline . She synthesized data from 15 studies, covering nearly 34,000 non-demented people, followed for 1 to 12 years. During this period, 3,210 cases of reduced mental capacity were recorded.
The most physically active people had a 38% reduced risk of being affected. Those who maintained a low to moderate level of activity were also protected, with a 35% reduced risk compared to those who were inactive. Sport is also one of the approaches to reduce the risk of developing a neurodegenerative condition such as Alzheimer’s and Parkinson’s disease, or to alleviate the signs.
BDNF, Mediator Of The Benefits Of Sport On The Brain
Several mechanisms can explain the benefits of sport on the brain. Physical exercise improves blood circulation and oxygen supply within brain tissues and reduces levels of stress and inflammation… But these are not the only factors at play. It also acts on the production of an essential compound for the cerebral sphere, brain-derived neurotrophic factor (BDNF).
BDNF is a major member of the neurotrophin family, a protein responsible for the growth, survival, and differentiation of cells belonging to the nervous system. In the brain, the highest levels of BDNF are found in the neurons of the hippocampus, a region involved in learning and memory phenomena. It is also present in significant quantities in the amygdala, cerebellum, and cerebral cortex.
Protection And Formation Of New Neurons
BDNF exerts its beneficial effects by binding to a receptor present on the surface of neurons, the tyrosine kinase receptor (TrkB). It then triggers cascades of reactions within them. One of the activated pathways – the Ras/MAPK/ERK signaling pathway – is involved in neurogenesis, in particular through the activation of transcription factors called CREB.
The ability to form new neurons from stem cells persists into adulthood in certain regions of the brain, particularly in the hippocampus. This phenomenon is important for maintaining brain functions over time. BDNF also promotes the development of structures that allow neurons to communicate with each other, axons, and dendrites. It thus contributes to cerebral plasticity, the ability of the brain to modify the connections between its neurons to carry out new learning or recover after trauma.
BDNF also plays a protective role, promoting neuronal survival through the IRS-1/PI3K/AKT signaling pathway. It leads to the neutralization of compounds that promote cell death such as the Forkhead transcription factor or BAD proteins. The latter has recently been implicated in the development of Alzheimer’s disease.
Reduced BDNF Levels And Impaired Brain Health
Levels of BDNF circulating in the body tend to decrease with aging. This rarefaction is associated with a reduction in the volume of the hippocampus and the occurrence of memory problems. Its levels are also lowered in most neurodegenerative diseases and people with depression. It therefore appears essential to maintain satisfactory levels of this compound to maintain brain health.
Myokines Boost BDNF Production
Several myokines appear to be able to stimulate the production of BDNF in the brain. BDNF itself is considered a myokine because active muscles can produce it. However, it is not released into the bloodstream; it can only act locally, providing specific benefits to the muscle.
The Neuroprotective Action Of Irisin
Irisin is one of the main myokines playing an anti-aging role in the brain. During exercise, it is released from the muscle from a protein called FNDC5 and released into the bloodstream. It crosses the blood-brain barrier and adds to the stock of irisin produced within the organ itself under the effect of exercise.Â
A team recently became interested in its potential protective effect in the context of Alzheimer’s disease. In patients, the quantity of irisin present in the fluid in which the brain bathes is lower than in people with good brain health. The researchers used a mouse animal model of Alzheimer’s disease to better understand the action of myokine. These mice also have an irisin deficiency in the brain. When it was corrected with direct input to the hippocampus, their memory problems improved.Â
The same benefits were observed when irisin was administered into the bloodstream, confirming the machine’s ability to cross the blood-brain barrier and act on the cerebral sphere. A study conducted on 50 women over 65 years old showed that resistance training, two one-hour sessions per week for 12 weeks, is a good way to raise the level of irisin circulating in the body. the organism.
Cathepsin B Improves Cognition
The beneficial effects of sport are also relayed by cathepsin B. Its absence, combined with that of another cathepsin (cathepsin L), results in a spectacular degree of brain atrophy. Work has shown that cathepsin B levels increase in muscle and blood in mice subjected to running activity. In response, the formation of new neurons is stimulated in the hippocampus of animals, whose spatial memory improves.
At least in those sensitive to the action of cathepsin B: in a line of mice deprived of its action following genetic manipulation, sport cannot fulfill its positive role on the brain. Through experiments on neural stem cell cultures, researchers were able to prove that the effects of cathepsin B occur through the stimulation of BDNF production.
The final stage of their study consisted of verifying that these results can be transposed to humans. Volunteers underwent 4 months of training consisting of treadmill running sessions. At the end of this period, the concentration of cathepsin B increased, with notable benefits on memory.
Ketone Bodies Complement The Action Of Myokines
Another type of compound contributes to the favorable effects of sport on the brain. This is β-hydroxybutyrate (BHB), a ketone body produced by the liver from fatty acids when glucose is lacking, and used as an alternative energy source. Discharged into the bloodstream, it can reach the brain. In a study in mice, researchers showed that BHB accumulates in the hippocampus of animals after a race and shed light on its effects.
BHB opposes the action of certain enzymes, histone deacetylases (HDAC) 2 and 3. Histones are proteins around which DNA wraps to form a compact structure called chromatin. HDACs are responsible for the removal of acetyl chemical groups from histone tails. In this way, they maintain chromatin compaction, which prevents gene expression. As BHB inhibits their action, this obstacle is removed and the DNA becomes accessible.
This action makes it possible to restart the production of BDNF. The administration of BHB, initiated in the middle of life in rats, thus makes it possible to improve learning abilities and working memory performance during aging. It also exerts neuroprotective effects in animal models of Parkinson’s and Huntington’s disease.
To data, data in humans is still rare. A study evaluated the effects of training with elastic bands, three days a week for 1 hour, over 4 weeks in elderly people. In participants who had low BHB blood levels before training, the levels improved with physical activity. A slight positive association between BHB levels and cognitive functions then appeared.
Read Also: Why Are We Stronger When We Are Fat?