Changes in selected exerkines concentration post folk-dance training are accompanied by glucose homeostasis and physical performance improvement in older adults – Scientific Reports

The main finding of the current study is that a 12-week folk-dance training performed by older adults significantly improved insulin sensitivity indicators with a significant drop in BDNF and the rise of irisin concentrations. Additionally, CAF, a potential marker for muscle atrophy, resulted in a reduced association with improved physical performance. It is worth to note that such beneficial effects in insulin sensitivity were pronounced, especially among those subjects who presented the worse condition (i.e., frank insulin resistance) at baseline.

The improvement in insulin sensitivity and resistance indicators was visible mainly in HOMA-IR, HOMA-%S, and QUICKI. The positive effects were more pronounced in the folk-dance training group compared to the balance training group, among whom only a tendency to improve insulin sensitivity indicators was observed. The discrepancies between groups may result from slight, although not significant, differences in baseline values of these parameters. These results reflect the findings of previously published research, where the positive effect of physical training was more pronounced among people with type 2 diabetes, hypertension, hyperlipidemia, or metabolic syndrome. Indeed, the recorded reductions in total cholesterol, LDL, fasting insulin, and HOMA-IR were not as pronounced in healthy subjects²⁰. Further, the latest studies indicated that the cut-off point of HOMA-IR for predicting the prevalence of metabolic syndrome is 1.8, and a value of 1.62 was obtained for identifying individuals at risk of IR^30,31. Both training groups in the current study are above this cut-off point. Thus, we could summarize that moderate-intensity aerobic exercise effectively counteracts risk factors for CVD and glucose metabolism indexes.

Together with beneficial changes in insulin sensitivity registered in our trained groups, we noted the reduction of blood pressure. Although the awareness of the need for physical activity is growing, the elderly may be afraid of undertaking regular physical activity. Both resistance and long-term aerobic training have been commonly suggested to reduce blood pressure in middle-aged individuals with pre-hypertension and frank hypertension³². The magnitude of blood pressure reduction observed after physical training might be comparable to those induced by first-line anti-hypertensive drugs³³. Our results supported these observations and proved that both moderate-intensity training programs effectively reduce blood pressure. The potential mechanism underlying this effect may be the aerobic exercise-induced increases in nitric oxide (NO) bioavailability, consequently improving endothelial function and endothelium-dependent vasodilation³².

Additionally, we hypothesize that the amelioration in insulin resistance was associated with a reduction in BDNF concentrations.The primary function of BDNF is to regulate neurogenesis in the brain; however, it has also been shown to have a pivotal role in the regulation of peripheral metabolism, especially energy balance and insulin sensitivity³⁴. Although the mechanism of action of BDNF in the central nervous systems quite well known, the peripheral pathways are not well understood. A novel metabolic pathway has been presented by Fulgenzi et al. It has been proposed in a mouse model that the BDNF receptor TrkB.T1 is expressed by pancreatic β-cells where it regulates insulin release¹⁴. Previous human research has shown that low circulating concentrations of BDNF are associated with insulin resistance, type 2 diabetes, and cognitive impairments¹². However, Boyuk and co-workers have also observed contradictory results, who found higher serum BDNF concentration in T2M patients and a positive correlation with HOMA-IR and triglycerides³⁵. It has been suggested that BDNF, through crossing the blood–brain barrier, may shift to the central nervous system and ameliorate the detrimental effects of insulin resistance in the brain as an antioxidant and neurotrophic factor^36,37.

The results from studies conducted on humans are ambiguous regarding the relationship between BDNF and long-term exercise protocols. No effects³⁸, enhancement in circulating BNDF concentration^15,39, and decrease have been observed⁴⁰.Previously published studies indicated that the post-exercise increase in BDNF concentration was associated with improved mood, cognitive functions, and quality of life^41,42. However, the elevation of BDNF and improvement of cognitive functions depended on the subjects’ age, the intensity of exercise, and metabolic factors, including, for instance, peripheral lactate concentration, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor levels (VEGF)⁴³. When considering the high-intensity exercise modality, most of these observations were about young, healthy subjects. In agreement with previous results⁴⁰, our study indicates that serum BDNF concentration decreased after aerobic training, regardless of the type, associated with the reduction in HOMA-IR and the increase in QUICKI indexes.

Another exerkine that may regulate insulin resistance in response to physical training is irisin. Irisin is expressed in skeletal muscle and other tissues and seems to induce a brown-like phenotype in some white adipocytes, which improves multiple metabolic parameters by increasing energy expenditure⁴⁴. Therefore, irisin could potentially protect against different conditions such as cardiovascular diseases, type 2 diabetes mellitus, or fatty liver disease. In the current study, we observed an amelioration in insulin resistance, especially in the dance training group, with a positive association with circulating irisin, supporting the hypothesis of an insulin-like action of irisin. Irisin, indeed, enhances the expression of genes involved in glucose transport and lipid metabolism in myocytes (GLUT4, HK2, and PPARA), inhibits the expression of genes that are involved in glycogenolysis or gluconeogenesis and downregulates proteins associated with insulin resistance pathway^45,46.

Along with insulin sensitivity improvement, the reduction of the systemic immune-inflammation index was evidenced in the balance group and a trend to reduction in the folk-dance group. In the last published review, authors pointed out that irisin-mediated alterations in cytokine production results in reduced macrophage migration and infiltration, vascular leukocyte adhesion and migration, and acute phase inflammatory response⁴⁷. Thus, it cannot be ruled out that the drop in SII was the effect of irisin’s action. The reduction of the SII index and changes in irisin have particular meaning due to the potential role of irisin in obesity-related cancer prevention as well as in osteoporosis and neurodegenerative diseases- commonly noted among aged people⁴⁸. Noteworthy, sarcopenia’s pathophysiological mechanism(s) contemplates the deterioration of the homeostatic systems, including the immune system. In opposition to the previous observation, any alternations were recorded in other pro-inflammatory cytokine IL-18⁴⁹ in the current study. Also, Gomarasca et al. did not indicate changes in circulating IL-18 concentrations in obese men and women following a 12-week moderate-intensity aerobic NW training program⁵⁰. However, among our subjects at baseline, a significant positive correlation was noted between IL-18 and visceral fat area, insulin, HOMA-IR, and triglycerides, and a negative correlation with HOMA-%S and QUICKI index. These results suggest that IL-18 could take part in the pathogenesis of obesity and insulin resistance, but it may not be sensitive to exercise intervention.

Although we did not determine muscle mass, our study focused on motor and functional balance test results (TUG and 6MWT). In both training groups, together with shifts of BDNF and irisin, the amelioration of these muscle functions was recorded. As irisin has been suggested as muscle wasting and muscular performance biomarker²³, these changes are significant since sarcopenia (the decline of fibers numbers and its size reduction) and dynapenia (reduction of strength) are highly prevalent in the elderly⁵¹. The scientific data point out that dynapenia precedes the process of sarcopenia, which is expressed by weakening motor abilities. Thus, the attenuation of this drop and the improvement of glucose homeostasis can be considered a preventive strategy against sarcopenia. Therefore, changes in these two proteins may indicate a positive effect of this training on preventing age-related loss of muscle mass.

Among the proteins considered as biomarkers of muscle atrophy and sarcopenia analyzed in this study—myostatin and CAF, only the latter substantially changed. Although previous studies showed a reduction in myostatin concentration, we did not observe such an effect. However, different results have been reported depending on sex, age, and exercise type (aerobic or resistance)⁵². The myostatin decrease was mainly observed after resistance forms of training⁵³. Significant post-training changes have been noted in CAF—one of the best indicators of neuromuscular junction integrity and thus may be a potential biomarker for the progression of age-related functional decline and muscle atrophy²⁰.CAF is associated with one of the mechanisms of functional deterioration in aging—a decline in neuromuscular junction integrity. This pathology leads to sarcopenia development and worsening in physical performance²⁴. The results of our study suggest that dance training may be effective in coping with functional decline related to aging via the reduction of CAF concentration. Only a few studies assess changes in circulating CAF levels following physical exercise^20,25. It should be indicated that previous researches show both increases, no effects, and decrease in circulating CAF concentration after exercise interventions. One of the previous researches indicated that one year of physical activity intervention combining moderate-intensity walking, strength, and balance exercises did not reduce CAF concentration²⁰. On the other hand, Fragala and co-workers observed that a 6-week resistance training increased CAF concentration in a group of elderly²⁵. However, this study assessed the resistance form of training. One study confirmed our observations and indicated that recreationally active aged individuals, who regularly practiced dance for more than 3 years, had significantly lower CAF concentration compared to their counterparts involved in other aerobic physical activities. Additionally, elderly dancers demonstrated better dynamic balance and functional performance²⁶. In the current study, a significant decrease in CAF concentration was observed in the dance training group, with an improvement in dynamic balance and physical performance, measured by TUG and 6MWT tests. Somehow, in the balance training group, a tendency to reduction in circulating CAF was also observed; however, this result was not statistically significant. The obtained results suggested that dance training is more effective in protecting from NMJ degeneration. We are far from speculating, but dance training may induce greater neuroplasticity and NMJ health than resistance or aerobic training since it involves both motor and sensory, cognitive and coordinative⁵⁴. Moreover, dance training belongs to creative activities.

This study presents some limitations that should be highlighted. Future studies should include assessing cognitive functions to evaluate if the changes in exerkines are related to cognition improvement. However, for this purpose, previous studies, including ours, indicated that dance training is an effective method to improve cognitive abilities²⁹ due to the engagement in sensory, cognitive, and coordinative functions⁵⁴.

Overall obtained data indicated that both training programs effectively improve physical performance, dynamic balance, and inflammatory status and reduce high blood pressure. However, folk dance appears to be more beneficial in ameliorating insulin resistance. The changes in response to training interventions are connected with shifts in BDNF, irisin, and CAF concentrations. Since there is limited data regarding the direct connection between BDNF, irisin, and CAF in humans, obtained results have particular meaning and fill the gaps in this research area.