Volume 27, Issue 2 (Spring 2021)                   Intern Med Today 2021, 27(2): 164-181 | Back to browse issues page

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Taheri F, Fathi M, Hejazi K. The Effect of 10 Weeks Core Muscle Training on Levels of Follistatin, Myostatin, and Pain in Elderly Women. Intern Med Today 2021; 27 (2) :164-181
URL: http://imtj.gmu.ac.ir/article-1-3544-en.html
1- Department of Sport Physiology, Faculty of Sport Sciences, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran.
2- Department of Sport Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran. , mfathei@um.ac.ir
3- Department of Sport Physiology, Faculty of Sport Sciences, Hakim Sabzevari University, Sabzevar, Iran.
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1. Introduction

Changes in skeletal muscle mass are among the inevitable old age problems and are associated with progressive skeletal, muscular weakness [1]. Because of the growth of the elderly population, loss of body mass and tissue has become significantly more prevalent, which is one of the structural-postural changes due to aging [2]. If muscle mass begins to decline, symptoms of decreased functional independence and back pain will gradually increase with age. This decreasing trend is intensified by having bad habits [3, 4]. However, improving lifestyle such as following a proper diet and exercising are solid and appropriate ways to deal with this erosive process [2, 5]. Many studies have examined muscle changes that occur with age. These studies have found that aging is associated with an increase in atrophy and muscle weakness of the lower extremities more than the upper extremities [6]. Also, there is an inverse relationship between aging and the size of the muscles of the central part of the body (abdomen and back) [7].
On the other hand, several studies have shown that muscle weakness is associated with musculoskeletal pain, such as back pain [8]. Because with increasing age, the muscles of the central part of the body, such as the multifidus muscle, become weak and atrophic, and this weakness can cause Low Back Pain (LBP) [9]. Therefore, the decrease in muscle mass during the aging process is an indirect but very influential factor in causing LBP [8]. Besides, losing muscle mass is associated with a decrease in physical function of the elderly, which affects their quality of life [2, 10].
Myostatin is a secretory factor and a member of a large family of secretory growth factors and has a critical negative regulatory role in skeletal muscle growth and homeostasis, which is secreted into the bloodstream as an endocrine agent after expression in skeletal muscle. Myostatin exerts its inhibitory effect (inhibition of proliferation and differentiation of satellite cells) on the surface of muscle cells by binding to the activin receptor and ultimately reducing muscle mass [11]. It has been observed that the expression of myostatin increases during periods of inactivity, and also the inhibition of serum myostatin leads to an increase in strength and muscle mass [12]. 
Another factor related to muscle mass that can be mentioned is follistatin. It is a single-chain polypeptide with diverse functions and is a member of the large family of growth factor-beta, the largest family of secreted growth factors, differentiation, and homeostasis of the body. This family plays a significant role in regulating and promoting the growth of body tissues [13]. Essential roles of follistatin include neutralizing the actions of growth factor-beta transporter proteins, including myostatin, tissue growth and differentiation, and regeneration and repair of damaged tissues [13].
Recent research has shown that various exercises can increase follistatin and reduce myostatin [14]. Santos et al. examined the effect of eight weeks of resistance training in different ways (including high and low-intensity squats) on the expression of myostatin gene inhibitors in active men. The subjects were grouped in strength training, resistance training, and controls. The researchers concluded that the expression of myostatin signaling pathway inhibitors was increased [15]. Yarahmadi et al. evaluated the effectiveness of core stability exercises on functional disability, dynamic balance, and lumbar-pelvic proprioception in patients with non-specific chronic LBP and concluded that a significant improvement was observed in functional disability, dynamic balance, and proprioception of the core stability of the exercise group [16]. By examining the effect of 6 to 12 weeks of core stability training on the lumbar joint position sense in 38 patients with LBP, Pantoma et al. concluded that core stability training improved the sense of lumbar joint position and reduced pain and functional disability [17]. Rastegar Moghaddam et al. reported that performing 10 weeks of core stability exercises significantly increased the longitudinal and transverse cross-sectional areas of the multifidus muscle. On the other hand, the subjects’ level of pain in the group of core stability exercises in the fifth and tenth weeks compared to the beginning of the intervention was significantly reduced [18]. After studying the effect of eight weeks of elastic band resistance training on serum myostatin and body composition of 26 older women, Vatankhah Khozani et al. concluded that the training significantly reduced the percentage of fat and myostatin level in the intervention group compared to the control group [19].
In summary, very little research has been done on the different forms of exercise, and which exercise method can have the most positive effects on the follistatin and myostatin factors. Regarding the effects of different training methods, especially core stability training exercises, there are still ambiguities about how these exercises affect physiological factors such as follistatin and myostatin. Different exercises can have various effects on the ratio of follistatin to myostatin, anaerobic function, and fatigue index. However, no research has investigated the difference between core stability training exercises on these indicators. Thus, we decided to answer whether core muscle training exercises affect serum follistatin and myostatin, as well as the pain in women with chronic LBP. Therefore, the present study aimed to evaluate the effect of 10 weeks of core muscle training on the levels of follistatin, serum myostatin, and pain in women with chronic LBP.

2. Materials and Methods

 This research is a quasi-experimental study in which the experimental and control groups were compared with pre-test and post-test. The study population includes older women over 60 years (age range between 60 and 70 years) with chronic low back pain selected by the available and purposive sampling method. In the first stage, women were introduced to the nature and manner of cooperation with the study procedure. The inclusion criteria included chronic low back pain (more than 3 months), age over 55 years, body mass index between 25 and 30 kg/m2. The exclusion criteria included pregnancy, specific spinal abnormalities (spondylolysis or spondylolisthesis), lumbar scoliosis with an angle of more than 10 degrees, severe osteoarthritis of the knee, and severely debilitating diseases. Subjects voluntarily participated in the research based on the study conditions and consciously signed the consent form. The samples were then randomly divided into experimental (n‌=‌9) and control (n‌=‌9) groups.
To evaluate the body composition, we measured the subjects’ height with Seka height meter (made in Germany) with 5-mm precision accuracy. Their hips and waist circumferences were measured with a tape measure (Mabis, Japan) with 5-mm precision accuracy. Finally, we measured their body fat percentage and weight with a precision accuracy of 100 g using a bioelectrical impedance device (model InBody _720 / South Korea).
All measurements were performed while the subjects had abstained from eating and drinking four hours before the test. So their bladder, stomach, and intestines were empty as much as possible. The subjects were allowed to enter the project after cardiovascular examination, blood pressure measurement, and electrocardiogram registration by a specialist physician.
In this study, the numerical version of the Visual Analog Scale (VAS) was used to estimate the subjects’ pain intensity [20]. On the VAS, a horizontal line 100 mm long is presented with two extremes of painless (left) and severe pain (right) on either side of the line. Based on these two extremes, the person marks his pain status on the line. The amount of pain is calculated in millimeters. The interpretation of data obtained from VAS is as follows: the numbers 0-4 mm are painless, 5-44 mm is mild pain, 45-74 mm is moderate pain, and 75-100 mm indicates severe pain [20].
The Back Performance Scale (BPS) was assessed by a 15-point scale (Borg 6-20 points) (five tests). The tests on this scale included wearing socks, picking up paper from the floor, getting out of bed, leaning forward, and lifting a box. Each test had four answers, from simple (zero points) to difficult (3 points). In the test of the wearing sock, the person sits on a high bench so that her feet did not touch the ground. Then, he was asked to raise his feet to her abdomen by bending the knee and grasp the toes with both hands. In the test of picking paper from the ground, a person in a standing position was asked to remove the paper placed on the ground before her. In the getting out of the bed test, the person is asked to lay down and then sit without using her hands. In the leaning forward test, the person should stand with straight knees 10 cm apart and is asked to bring the hands as close to the ground as possible without bending the knees. In the box lifting test, the person should stand before the table with a height of approximately 76 cm and place a box weighing 5 kg on the floor and back on the table for 1 minute. Then, the number of repetitions was recorded. The maximum score was 15 and represented the person’s worst lumbar function, and the minimum score was zero, which represents the best lumbar function.
The exercise activity protocol was also implemented for 10 weeks and included eight types of core ground muscle exercises focusing on isotonic and isometric strengthening of the lumbar and multifidus muscle [18] (Figure 1). 

The core muscle exercises were as follows: A, Boat or contraction of the back muscles, without leaning on a chair, B: Deep breathing with chest muscle stretching and contraction of the back muscles without leaning on a chair, C: Isometric contraction in the muscles that open the waist, D: corrected crunches and sit-ups E: Bridge movement, F: lumber extension when lying on the stomach, G: Shoulder flexion and static strengthening of the muscles that stabilize the spine, H: Thigh flexion, In all exercises, remind the subject not to hold her breath and talk to the subjects constantly.
In this study, blood samples were collected 48 hours before the training session and 48 hours after it. The Sampling was performed between 6 and 7 AM after 8 to 10 hours of fasting. About 5 mL of blood were taken from the vein of the subject’s left hand in a sitting position and at rest.
To determine the amount of follistatin and myostatin, we used the ELISA method and laboratory kit of follistatin and myostatin (CUSABIO  Japan).
The collected data were analyzed by SPSS version 21. After ensuring the normality of the data distribution using the Shapiro-Wilk test and homogeneity of variances by Levene’s test, the correlated t test and Analysis of Covariance (ANCOVA) were used to compare intragroup and intergroup changes, respectively. The significance level was considered less than 0.05.

3. Results

The characteristics of the experimental and control groups are shown in Table 1

Table 2 shows that the changes of intragroup variables of weight (P=0.1), body mass index (P=0.9), body fat percentage (P=0.5), skeletal muscle mass (P=0.8) did not change significantly at the end of the training period. The relative pain scale (P=0.001) was significantly reduced. Follistatin (P=0.001) and myostatin (P=0.001) levels increased and decreased significantly at the end of the training period, respectively. But in the control group, these changes were not significant (P>0.05). There was a significant difference between the experimental and control groups in the intergroup mean variables regarding relative pain scale, serum follistatin, and myostatin (P<0.05). 

The changes in the intragroup means in the tests of rising from the bed (P=0.03), bringing the fingers to the ground (P=0.03), lifting the box (P=0.04), and the total score of lumbar function scales of women with chronic LBP decreased significantly at the end of the study period (P=0.02) (Table 3). Changes in mean intergroup variables in the tests of wearing socks, getting out of bed, bringing fingers to the ground, lifting the box, and total score of lumbar function scales are significantly different between the experimental and control group (P<0.05). 


4. Discussion

This study aimed to evaluate the effect of 10 weeks of core muscle training on the levels of follistatin, serum myostatin, and pain in women with chronic LBP. The present study results showed that core muscle training led to a significant increase in follistatin levels and a significant decrease in serum myostatin. Hoffman et al. also reported that three to six months of resistance training and elastic band training with dietary supplementation improved exercise performance and increased follistatin, decreased the ratio of follistatin to activin A, and did not significantly alter myostatin levels [21]. In the study of follistatin changes, the muscle’s anabolic response is consistent with previous studies [22, 23]. In other words, due to anabolic resistance and disruption of muscle anabolic signaling pathways, the muscles of the elderly do not respond like the muscles of young people to protein supplements and require more time and protein consumption [22]. More than 80% of protein synthesis after food intake is related to protein consumption and amino acids play an essential role in this process [24]. Follistatin is a positive regulator of muscle growth factor, and various studies have been performed to evaluate changes in this hormone in response to exercise.
After exercise, the levels of activin-follistatin gene expression in rat liver change, and activin mRNA levels decrease [25]. In general, few studies have examined muscle hypertrophy markers in response to core stability exercises in older women with LBP. The cellular and molecular mechanisms that transmit cellular signals, followed by muscle growth, are not yet fully disclosed. Exercise-induced muscle contraction is the process of converting a mechanical signal into a series of molecular events. These molecules regulate gene expression, protein synthesis, and protein breakdown by activating specific signaling pathways that include primary and secondary messengers, followed by muscle cell adaptation [26]. Primary messengers who initiate cascading processes include calcium current, redox potential, stretching, phosphorylation potential, and mechanical tensions. Muscle tension alone and independent of the increase in contractile activity can also stimulate protein synthesis through several pathways. Extracellular matrix stretching activates intracellular signals, leading to changes in gene expression and protein synthesis [27]. According to the results of the present study and previous studies, core stability training by balancing the positive and negative regulators of muscle growth can play a role in improving the physical condition of the elderly. By the decline of muscle growth regulators in old age, the inhibitory role of negative regulators, including myostatin, is more prominent [19]. Of course, it is also worth considering that older people have mobility limitations due to the problems created in the physiological and physical condition; therefore, applying the exercise load and maintaining the training duration face limitations that the use of this type of exercise can help these people more. Therefore, this type of training intervention helps rehabilitation and sports programs for the elderly [17].
 The present study results showed that core stability exercises lead to a significant reduction in the degree of pain and improved lumbar function in older women with chronic LBP. In the study of chronic LBP changes in older women, the multifidus muscle plays a stabilizing role in the spine and prevents the spine from bending. As we know, multifidus muscle atrophy is associated with low back pain [28]. The multifidus muscle is in a confined anatomical position. It is surrounded on both sides by transverse and shock-absorbing processes, and its volume and hypertrophy can increase only from transverse and superficial directions. This is the reason for the triangular shape of this muscle [29]. The cross-sectional area of ​​the multifidus muscle decreases with age, and if this muscle atrophy is compensated, chronic low back pain in older women can be reduced.
In studying the cause of chronic LBP, several etiologies have been stated, including atrophy, loss of strength, and mass of multifidus muscle due to aging [28, 30]. Thus, the weakness of abdominal muscles, deep trunk muscles, and lack of proper control of deep trunk muscles such as multifidus muscle are among the main etiologies [31]. Numerous studies have reported a reduction in LBP in response to exercise [32, 33]. However, the mechanism of this reduction is not well understood. Three theories are proposed to explain the mechanism of pain relief; 1) mechanical theory (increase of core strength and stability), 2) neurological theory (desensitization), and 3) acting theory (classified activity) [34]. In all these theories, exercise is a physical or behavioral tool that reduces the severity of pain and disability due to low back pain [34]. In mechanical theory, core stability exercise was performed for 10 weeks, and only after five weeks, the pain decreases significantly. Also, from the perspective of physiological adaptation to sports activity, neuronal adaptation, which is the first response of the neuromuscular system to sports activity [35], can be responsible for increasing strength and subsequently reducing chronic LBP in older women [22, 36]. Contradictory results are likely to be due to differences in the participants’ physiological conditions, health, duration, type and intensity of exercise, and nutritional status. Since this study had many limitations, including various diets, different adaptive responses to physical activity, a small number of subjects due to the withdrawal of some of them from participating in the present study, and individual differences, caution should be observed in interpreting the results.

5. Conclusion

In general, core muscle exercises led to a significant reduction in the relative intensity of pain. Follistatin and myostatin levels increased and decreased significantly at the end of the training period, respectively. The low back function also improved in older women with chronic LBP at the end of the training. However, due to the importance of physical activity in preventing and treating many pains, experts recommend exercise counseling to treat chronic back pain. Besides, exercise increases the strength and social participation of older women. Therefore, these interventions are a good treatment for chronic LBP, which is very common, especially among the elderly.

Ethical Considerations

Compliance with ethical guidelines

This study was approved by the Ethics Committee of theBojnourd University of Medical Sciences (Code: IR.IAU.BOJNOURD.REC.1395.023). 


The article was extracted from the MA. thesis of the first author at the Department of Sports Physiology, Faculty of Sports Sciences, Islamic Azad University of Bojnourd.

Authors' contributions

Implementation of the protocol: Fatemeh Taheri and Mehrdad Fathi; Final approval: All Authors; Conceptualization : Mehrdad Fathi; Data analysis, Writing – original draft, and writing – review & editing: Keyvan Hejazi.

Conflicts of interest

The authors declared no conflict of interest.


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Type of Study: Original | Subject: Physiology
Received: 2020/06/2 | Accepted: 2020/08/31 | Published: 2021/04/1

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