Background: Forest bathing and aerobic exercise are known to be factors that increase natural killer (NK) cell, but it is considered to provide a greater effect when the two factors are combined. To date, it has not been studied whether aerobic exercise combined with forest bathing can further increase innate immunocytes, including NK cell. Therefore, this study investigated the effect of aerobic exercise + forest bathing on NK cell and whether stress hormones (epinephrine and cortisol) are involved in this physiological process. In addition, this study tried to confirm whether the mixed effect of the two had a more positive effect on cardiorespiratory endurance as well as body composition in the elderly men. Methods: Thirty-two participants were randomly assigned to one of four groups: control group (CON, n = 8) which was not provided with any intervention, exercise group (EXE, n = 8) which performed treadmill exercises without phytoncide, phytoncide group (PHYT, n = 8) which was provided with phytoncide intervention, and exercise + phytoncide group (EXE + PHYT, n = 8) which performed treadmill exercises and was provided with phytoncide. Treadmill exercises and phytoncide exposures were performed for 45~60 min a day, 3 days a week for 12 weeks. Results: Compared with CON, (1) the leucocytes and lympocytes of EXE, PHYT, and EXE + PHYT showed positive changes. Specifically, total NK cells, NKT cells, and NKG2D + NK of the EXE + PHYT increased after 12 weeks of intervention. (2) The cortisol concentrations of EXE, PHYT, and EXE + PHYT showed decreasing changes, whereas the epinephrine concentration were significantly increased. (3) Although there were no changes in the muscle mass of EXE, PHYT, and EXE + PHYT, cardiorespiratory endurance was significantly increased in those groups. In addition, the body weight, fat mass, and fat percentage significantly decreased only in the EXE + PHYT. Conclusions: This study confirmed that forest bathing and aerobic exercise positively affected immunocyte function in elderly men. It also found that the improved results from forest bathing + treadmill walking were caused by an increase in cardiorespiratory endurance by increased epinephrine concentrations. In addition, this increased cardiorespiratory endurance can be interpreted as significantly reducing the body weight and fat in the group that participated in the exercise combined with phytoncide exposure.
As age increases, the function of immunocytes decreases, leading to cancer, disease, or death . Although the immunosenescence that occurs in the body may be a natural phenomenon, there are many ways to delay or inhibit this process. The human immune system has innate immunity and acquired immunity. However, innate immunity can protect the human body more effectively against cancer that can come from aging or substances that invade from the outside . Upon identification of danger or a foreign invader, innate immunocytes, such as natural killer (NK) cells, respond by destroying infected cells and releasing cytokines and chemokines to recruit additional cells to fight the infection and alter host tissues, a process commonly referred to as inflammation . NK cells are a type of leucocyte in the blood and are innate immunocytes that mainly produce and mature in the bone marrow to directly destroy cancer cells. There are a total of about 100 million NK cells in the body. The anticancer mechanism of NK cells is well known. That is, NK cells recognize abnormal cells, make holes in the cell membrane with perforin, and induce apoptosis by introducing granzyme B into the cytoplasm, or destabilize the osmotic pressure of the cytoplasm and excessive inflow of water and salt to cause cell necrosis .
In order to protect the human body from immunosenescence, the amount or sensitivity of innate immunocytes, including NK cells, must be improved. Efforts to increase the number and quantity of innate immune cells from the past to the present have been continued through scientists in many fields such as Immunology, Medicine, Pharmacy, Biology and Exercise Physiology. In particular, phytoncide emitted from trees located in the mountains has attracted much attention in the academic world as it is known to effectively destroy infected cells or tumor cells by increasing NK cells in the human body . Since several studies have shown that phytoncide increases the activity of NK cells [6, 7, 8, 9], phytoncide is expected to have anticancer and antiaging effects by increasing NK cells activity. Phytoncides are volatile substances that are emitted or secreted by plants to resist pathogens. It consists of phenolic compounds, alkaloids, and glycosides, including terpenes, which are the main components. Among the terpenes, monoterpenes have adrenal cortex stimulation, antiseptic, sterilization, and antiviral effects. Tannin, the second most abundant component in phytoncide, has detoxification, sterilization, hemostasis, and anti-inflammatory effects . When phytoncide is inhaled as a gas, it relieves stress, strengthens intestinal and cardiopulmonary functions, and has a sterilization effect. In addition, it is reported that phytoncide has an antibacterial effect, which can increase immunity.
It is also reported that physical exercise slows or prevents the aging process
by enhancing cardiorespiratory endurance and basal metabolic rate, as well as
improving immunocyte function [11, 12]. In particular, moderate aerobic exercise
is considered to have anticancer effects because it increases NK cells .
Crist et al.  reported that NK cell tumor cytotoxicity was
significantly improved after treadmill exercise was performed by elderly women.
Recently, Lee and Jee  reported that increasing muscular strength and
endurance through a resistance exercise for 12 weeks in cancer survivors could
improve adaptive immunocytes. In fact, the increase in NK cell activity due to
exercise is explored by regulating the autonomic nervous system and the action of
hormones caused by the body’s response to exercise. According to Tønnesen
et al. , there was no change in NK cell activity after cortisol
alone, but epinephrine alone or cortisol + epinephrine administration increased
NK cell activity. It can be considered that the epinephrine regulated by the
Here, we can speculate that exercising in the mountains with a high level of phytoncide can prevent the decline of immune function due to aging and activate the function of innate immune cells that destroy cancer cells. However, it was not easy to establish a scientific basis for such a theory due to the lack of an experimental environment or research manpower. Moreover, it is not known whether exercise while forest bathing is consistent with the exercise mechanism described in previous studies [17, 18]. Therefore, this study investigated the effects of aerobic exercise combined with forest bathing on the innate immuocytes including NK cells and receptors in elderly men. In addition, this study investigated how cortisol and epinephrine, which affect innate immunocytes, change as a result of exercise with abundant phytoncides, and whether aerobic exercise combined with forest bathing can improve their effects.
The participants were aged between 61 and 79 years from Seoul Seniors Tower in Seoul and Inje, Korea. All participants did not exercise regularly for over six months, but expressed willingness to improve their immunosenecense. The inclusion criteria included (1) no or minor early knee orsteoarthritis that is confirmed by the anteroposterior, weight-bearing, and short knee X-ray; (2) over 60 years of age; and (3) male. Exclusion criteria included: having a deformity of the knee, hip, or back; central or peripheral nervous system involvement; having a history of taking any medication including steroids or intra-articular injection within the previous 6 months; having undergone surgery within the previous 6 months; using a pacemaker; having internal metallic materials; having a history of impairment of a major organ system or a psychological disorder .
Specifically, all participants were assigned using random number tables and identification numbers upon recruitment. Initially, forty two elderly men enrolled in this study. Two participants were excluded from the process of grouping, and forty participants were randomized. In the experimental phase, two participants in the control group (CON), two participants in the exercise group (EXE), one participant in the phytoncide group (PHYT), and three participants in the exercise + phytoncide group (EXE + PHYT) were lost. Finally, a total of 32 participants were included in the study as shown in Fig. 1.
Participants’ allocation (consolidated standards for reporting of trials flow diagram).
Thirty-two participants who met the inclusion criteria were randomly assigned to one of four groups: a CON (n = 8) that was not provided with any intervention, an EXE (n = 8) that performed a treadmill exercise without phytoncide; a PHYT (n = 8) that was provided with phytoncide intervention; and an EXE + PHYT (n= 8) that performed a treadmill exercise with phytoncide provided. Participant characteristics are presented in Table 1.
|Groups without phytoncide||Groups with phytoncide|
|CON||EXE||PHYT||EXE + PHYT||X
|(n = 8)||(n = 8)||(n = 8)||(n = 8)|
|Body weight (kg)||72.98
|Muscle mass (kg)||34.09
|Fat mass (kg)||20.18
|Percent fat mass (%)||28.01
|Percent muscle mass (%)||47.03
|Body mass index (kg/m
|All data represents mean |
This prospective, cross-sectional randomized controlled trial was conducted in accordance with the Declaration of Helsinki (2013 version) and was approved by the ethics committee (September 1, 2018 to August 31, 2019; 2-1040781-A-N-012021024HR and Seoul Songdo Hospital; 2021-008) This study was registered in the Korean Clinical Research Information Service. Prior to the study, participants received detailed explanations regarding the study procedures and written informed consent was obtained from all participants. The participants were assessed at two different time points and two different places, including Seoul and Inje of Gangwondo, South Korea over 12 weeks. The purpose of this study was to investigate the effects of treadmill walking on cortisol, epinephrine, and NK cells and receptors in two areas with low and high levels of phytoncide, targeting elderly males of similar age groups. The assessment was performed before and after the intervention period. The participants involved in the PHYT and EXE + PHYT left in Inje, Gangwondo the day before the experiment, received intervention for 3 days and were allowed to return to their residence in the afternoon at the end of the week. To prevent communication among the groups at each location, the participants were classified according to their community areas. Moreover, the interventions and measurements were also scheduled at different times to prevent communication among the CON, EXE, PHYT and EXE + PHYT. The CON was scheduled at 10:00, the EXE at 12:00, the PHYT at 10:00, and the EXE + PHYT at 12:00. For the CON and PHYT, they gathered at the immune center at the scheduled time and performed only meditation while lying on a mattress for 60 min at each place. The assessments were performed at Week 0 and at Week 12. The intervention program consisted of treadmill walking, which was conducted 60 min a day, 3 consecutive days a week for 12 weeks. The independent variables in this study included forest bathing and treadmill walking, whereas the dependent variables consisted of leucocytes, lymphocytes, NK cells/receptors, epinephrine, cortisol, body composition, and cardiorespiratory fitness.
The weather and climate conditions were obtained through the Korea Meteorological Administration (https://www.weather.go.kr/w/index.do)  and information regarding phytoncide concentrations was obtained through the Korea National Institute of Forest Science (https://www.forest.go.kr/kfsweb/kfs/idx/Index.do) . The experiments in this study were conducted between June and August 2021. The environmental characteristics related to phytoncide concentration, temperature, humidity, and wind speed in the two locations are shown in Table 2.
|Average temperature (
|Average maximum temperature (
|Maximum temperature (
|Average minimum temperature (
|Minimum temperature (
|Average humidity (%)||72.67
|Minimum humidity (%)||37.33
|Average wind speed (m/s)||2.10
|Maximum wind speed (m/s)||7.83
|Maximum wind speed/direction (º)||190.00
|Maximum instantaneous wind speed (m/s)||15.97
|Maximum instantaneous wind speed/direction (º)||276.67
|Phytoncide concentration (pptv)||575.30
|All data represents mean |
The EXE and EXE + PHYT participated in a treadmill exercise in a supervised exercise program 3 days a week for 12 weeks. The treadmill exercise for EXE was conducted at the Exercise Immunity Center in Seoul where phytoncide was low, while the treadmill exercise for EXE + PHYT was conducted at the Exercise Immunity Center in Gangwon-do where phytoncide was high. During the treadmill exercise for EXE + PHYT, all doors and windows were opened so that fresh air with high phytoncide concentration could be inhaled. The elderly who participated in this study observed whether treadmill exercise was possible in advance, and participants in EXE and EXE + PHYT, who had to do this exercise, were allowed to exercise for a set period on the treadmill assigned to them. During exercise, four exercise prescribers observed the elderly at a close distance, and one observed the data transmitted from the heart rate clock through a laptop placed on the table. The dosage of the exercise regimen was determined through the FITT principle, wherein the frequency, intensity, time (duration), and type of exercise together quantify the total dose . In particular, when designing an exercise program, this study tried to prescribe 150 min of moderate-intensity, or 75 min of vigorous-intensity, exercise per week as suggested by Physical Activity Guidelines Advisory Committee , and is shown in Table 3.
|Items||Exercise types||Exercise training phases|
|0–3 week||4–6 week||7–9 week||10–12 week|
|Warm-up||Standing stretching||10 min||10 min||10 min||10 min|
|Work-out||Aerobic training||F||3 days||3 days||3 days||3 days|
|I||60% VO₂peak||70% VO₂peak||80% VO₂peak||85% VO₂peak|
|T||60 min||55 min||50 min||45 min|
|Cool-down||Sitting/Lying stretching||15 min||15 min||15 min||15 min|
|F, frequency; I, intensity; T, time; VO₂peak, peak oxygen consumption.|
As shown in Table 3, EXE and EXE + PHYT began with warm-up conditioning for 10 min as instructed by the researcher. Next, all participants performed the workout. Aerobic exercise training was performed 3 days a week, every other day (Monday, Wednesday, and Friday), and the intensity of exercise included walking or running at 60–85% of VO₂peak. For this, a heart monitor was used to maintain a heart rate according to the exercise intensity. Phase I started with 60 min of walking and progressed to 45 min of brisk walking and light jogging in Phase IV, where the program ended. The pulse rate was measured during the treadmill exercise using the Xcoach system (Spornix, Seoul, Korea). The Xcoach system is a device that can analyze the exercise intensity and fatigue recovery ability through real-time heart rate/exercise intensity wireless monitoring of the subject. As shown in Fig. 2, it consists of a heart rate measuring chest belt, data transmitter/receiver, and an exercise intensity display wristwatch, and it is composed of a laptop (program installation) that receives the data transmitted from the transceiver. Before the exercise, all subjects were instructed to place a sensor (heart rate checking) in the center of the chest and fix the torso with a band. And the heart rate transmitted from the sensor on the wristwatch was derived from the exercise intensity, and it was received and quantified by a laptop computer. Lying stretches were performed for 15 min after exercise.
Device for checking a heart rate.
All subjects were prohibited from exercising and taking drugs for more than 12 h
before blood collection, and after fasting, about 10 mL of blood was collected
from the antecubital vein, centrifuged at 3000 rpm for 15 min, and stored in a
Flow cytometry analysis of NK cells and receptors in the elderly. A front scattered light (FSC)-A and side scattered light (SSC)-A plot was used to identify nucleated cells. (A) A lymphocyte gate was set based on the size and granularity of the cells. (B) Single cells were gated, and doublets were excluded. (C) CD14+ macrophages were excluded. (D) NK cells were defined as CD3-CD56+. (E) Two NK cell subsets were identified: CD16+ and CD16- NK cells. NKG2D and KIR2DL3 were defined as CD314 and CD158b, respectively.
Subpopulations of human peripheral blood cells were analyzed as follows: 50
For the accuracy of the test, participants were asked to limit food, alcohol and
caffeine intake prior to the test. They were also asked not to exercise on the
day before the test and to urinate just before the test. The body composition
including height was measured by Inbody 770 (Biospace Co., Ltd., Seoul, Korea).
All participants took off all metal objects attached to their bodies.
Participants were asked to stand on the device and hold the handles for
2~3 min. Only body weight, muscle mass, fat mass, percent fat,
and body mass index were selected from among various data to be derived from the
body composition test and used for analysis. Cardiorespiratory endurance of
participants was estimated by obtaining maximum oxygen uptake (VO
During the entire study period, all subjects consented not to change their daily diet and activities. In order to investigat this, the researchers conducted weekly evaluations using the following two methods and informed them. First, a diet diary was given to them for recording what they had in the morning, afternoon, and evening. A researcher input the type and amount of diet into CAN-Pro 5.0 (http://canpro5.kns.or.kr; Korean Nutrition Society, Seoul) every day, calculated the calorie intake, and evaluated it every 3 weeks. Second, the activity status in daily life was checked with the short-form type of International Physical Activity Questionnaire . Participants’ physical activity levels were recorded over the past last weeks. Metabolic equivalents (MET)/min (kcal/kg/min) for daily calorie output was calculated every 3 weeks. The total scores were calculated by adding the time and frequency of walking, moderate-intensity activity, and vigorous activity. The recorded calorie intake and output data were averaged at Week 3, 6, 9, and 12 and analyzed at Week 0 and Week 12.
Sample size was determined using G*Power program , which calculated with a
priori effect size (0.4) of f
As shown in Table 1, age, height, and body composition among the four groups were not significantly different prior to the experiment. There were also no significant differences in temperature, humidity, and airflow between the two experimental places, but a significant difference in phytoncide concentration existed as shown in Table 2. That is, the demographic and environmental variables of this study indicated homogeneity of this study. Moreover, there were no significant differences in the controlled variables, such as the daily amount of diet and physical activity, as shown in Table 4.
|Daily physical activity (kcal)|
|Daily dietary amount (kcal)|
|All data represents mean |
As shown in Table 5, VO₂peak before the start of the study showed a significant positive correlation with total NK cells (rho = 0.477) and NK T cells (rho = 0.374). After the study completion, VO₂peak showed a significant positive correlation with total NK cells (rho = 0.403), NK T cells (rho = 0.396) and epinephrine (rho = 0.396). Before the start of the study, total NK cells showed no significant correlation with NK T cells, cortisol and epinephrine. After the study completion, total NK cells showed significantly positive correlation with NK T cells (rho = 0.521) and epinephrine (rho = 0.454), whereas a negative correlation with cortisol (rho = –0.500). Moreover, NK T cells showed a positive correlation with epinephrine (rho = 0.603), and cortisol showed a negative correlation with epinephrine (rho = –0.382).
|VO₂peak||Total NK||NK T||Cortisol||Epinephrine|
|VO₂peak, maximal oxygen consumption; NK, natural killer cell.|
As shown in Table 6, although neutrophils and KIR2DL3 + NK did not show significant interactions between group and time, there were significant changes in leucocytes, lymphocytes, total NK cells, NKT cells, and NKG2D + NK after 12 weeks. Among those that showed an interaction effect, leucocytes showed a similar tendency to increase in EXE-PHYT, EXE, and PHYT, but decreased only in CON in post-hoc test. Lymphocytes increased significantly in EXE-PHYT and PHYT, increased slightly in EXE, and decreased in CON. Total NK cells, NKT cells, and NKG2D + NK in the post-hoc test showed the highest changes in EXE-PHYT, followed by EXE, PHYT, and CON sequentially.
|Time||Groups||Repeated ANOVA (F)||η²|
|Total NK cell||Pre||8.93
|NKG2D + NK||Pre||53.50
|KIR2DL3 + NK||Pre||34.83
|All data represents mean |
After the experiment, cortisol and epinephrine concentrations showed significant
changes in the four groups. As shown in Fig. 4 (left), the cortisol concentration
of CON at baseline was 16.43
Differences of cortisol and epinephrine concentrations between
times and groups. In the figure, CON, control group; EXE, exercise group without
phytoncide; PHYT, phytoncide group; EXE + PHYT, exercise + phytoncide group with
As shown in Fig. 4 (right), epinephrine concentration of CON at
baseline was 38.81
As shown in Table 7, although muscle mass did not show the significant interaction between group and time, there were significant changes in body weight, fat mass, percent fat, and body mass index (BMI) after 12 weeks. Although the body weight including fat mass, percent fat, and BMI showed an interaction effect, only fat mass and percent fat showed significant differences between groups in post-hoc test. That is, the fat mass of CON and PHYT was similarly high, while that of EXE and EXE-PHYT was similarly low. Specifically, in the case of fat mass, EXE-PHYT and EXE showed the smallest decrease, while CON and PHYT showed an increase. The percent fat showed similar results to fat mass.
|Time||Groups||Repeated ANOVA (F)||η²|
|Body mass index||Pre||25.00
|All data represents mean |
As shown in Fig. 5, VO₂peak showed significant changes in the four groups after
the experiment. The VO₂peak in CON at baseline was 34.58
Differences of physical fitness between times and groups. In the
figure, CON, control group; EXE, exercise group without phytoncide; PHYT,
phytoncide group; EXE + PHYT, exercise + phytoncide group with phytoncide;
This study was conducted while controlling for daily activities and diet in elderly men for 12 weeks. During the experiment, aerobic exercise was performed for 45~60 min according to the principle of gradual overload 3 days a week. Characteristically, the following results in this study were obtained as a result of executing the program at the same time in both locations, one with high phytoncide and one low phytoncide concentration. Prior to the full-scale analysis, this study analyzed the correlation between the variables. As a result, VO₂peak showed a significant positive correlation with total NK cells and NK T cells before and after the experiment. At the end of the study, total NK cells showed a significantly positive correlation with NK T cells and epinephrine, whereas a negative correlation with cortisol. Moreover, NK T cells showed a positive correlation with epinephrine, and cortisol showed a negative correlation with epinephrine. This study also found that forest bathing and aerobic exercise positively affected immunocyte function and that the improved results from forest bathing + aerobic exercise were caused by an increase in cardiorespiratory endurance and epinephrine. In addition, this increase in cardiorespiratory endurance can be interpreted to have significantly reduced the body weight, fat mass, fat percentage, and BMI of the two groups that participated in the treadmill exercise.
Short-term or long-term exercise and training affect the rise and fall of
hormone levels. In particular, these two hormones analyzed in this study are
major components of the physiological stress response  and are usually
excreted in response to exercise. Basically, cortisol is a corticosteroid hormone
that promotes gluconeogenesis and acts on fat and water metabolism. It is a
stress hormone that promotes muscle contraction due to excitement in nervous
tissue. On the other hand, epinephrine is a type of catecholamine and is one of a
group of similar compounds that exhibit sympathetic excitatory action. The blood
level of these hormones can be interpreted as a change in the secretion rate of
the hormone secreted by the endocrine gland. The increase in circulating plasma
hormones during exercise depends on an increase in secretion rate, a decrease in
circulating or clearance of the hormone, a decrease in plasma volume due to
sweating, or one or more of a combination of factors. Among the combined effects,
the phytoncide used as an intervention in this study caused significant changes
in stress hormones and NK cells, even without exercise. In particular, the
leucocyte and lymphocyte concentrations of the PHYT that received only phytoncide
increased to a similar degree after 12 weeks as that of the EXE-PHYT that
received both phytoncide and aerobic exercise. In other words, although
phytoncide can affect leucocytes and lymphocytes to some extent, when combined
with aerobic exercise, the degree of exposure to phytoncide increases, suggesting
that more beneficial effects can be provided. As shown in Table 5, the leucocytes
concentration in CON was 4.96
During exercise, cortisol rises after strenuous exercise. The heart and blood
vessels play an important role in stability and reflex control during exercise to
increase cardiac output, heart rate, and blood pressure. Generally, cortisol
concentration returned to pre-exercise levels within 2~3 hours
after a single bout of exercise. Cortisol is a corticosteroid hormone that
passively inhibits the secretion of adrenocorticotropic hormones from the
hypothalamic-pituitary-adrenal axis . In addition, it is involved in the
metabolism of energy substrates, promotion of the synthesis and secretion of
other hormones, regulation of reproductive functions, nervous system, immune
function, and adaptation to stress such as exercise, while also playing an
important role in synthesizing catecholamines at the sympathetic nerve endings
. It is also known that an abnormally high concentration of cortisol
suppresses fever and causes loss of immunity. High cortisol levels ultimately
cause tissue destruction and negative nitrogen balance in the body. Although the
effects of exercise on cortisol levels show somewhat contradictory results, it is
generally accepted that exercise increases them. On the other hand, around
70~80% of the epinephrine secreted from the adrenal medulla
plays a role in the cardiovascular system, expanding cardiac output, myocardial
contractility, heart rate, muscles and cardiovascular blood vessels .
Epinephrine increases the blood glucose concentration by decomposing the glycogen
stored in the liver and muscle while freeing fatty acids to increase the blood
fatty acid concentration, thereby promoting the metabolic rate . In this
study, while combining forest bathing with aerobic exercise decreased cortisol
levels, epinephrine increased. Contrary to the results of previous studies in
which epinephrine concentration decreased during long-term training, this study
showed increased epinephrine concentration, which is thought to be due to the
effect of phytoncide exposure through forest bathing to some extent. In other
words, it is thought that long-term forest bathing combined with aerobic exercise
affected the metabolic effect of increasing epinephrine and inducing sympathetic
nervous system activity, thereby increasing the mobilization of energy substrates
and the rate of energy consumption. These results can also be seen in the body
weight, fat mass, percent fat, and BMI which were significantly changed after 12
weeks. As shown in Table 7, after the end of the experiment, the body weight of
CON increased ~3.91%, while the body weight of EXE, PHTY and EXE
+ PHTY decreased ~2.71%, ~0.24% and
~4.16%, respectively. In particular, the muscle mass of EXE and
EXE + PHTY, which performed treadmill exercise, increased 4.53
Previous studies reported that forest bathing enhanced NK cell activity, the
number of NK and NKT cells, and intracellular anti-cancer proteins in lymphocytes
[35, 36, 37]. Li et al.  reported that the increased NK activity was the
leading cause of aromatic volatile substances derived from trees, called
phytoncides, such as
This study also found that the NKG2D + NK concentrations of the EXE, PHYT, and EXE-PHYT increased, while KIR2DL3 + NK receptors were not changed compared with those of CON. NK cell activation receptors recognize ligands expressed when target cells are in an abnormal state. Typically, the NKG2D + NK receptor detects UL16-binding proteins (ULBPs) and major histocompatibility complex (MHC) class-I-chain-related protein (MIC), which are intracellular molecules whose expression is increased during DNA damage, cancer, and infection in the human body [6, 42]. On the other hand, inhibitory receptors of NK cells measure the presence or absence of intracellular molecules that are constitutively expressed on the surface of target cells . Typically, NK cells express inhibitory receptors specific to MHC class I. If the target cell is deficient in MHC class I, a signal that can inhibit NK cell activity is not transmitted. An MHC class I-specific inhibitory receptor expressed in NK cells includes human KIR (killer cell immunoglobulin-like receptor). In addition, the existence and role of many other activation/inhibitory receptors that can regulate the activity of NK cells have been reported. Therefore, to understand and effectively regulate the activity of NK cells [44, 45], it is essential to elucidate how the activity of NK cells is regulated by the combination of these various receptors [8, 9]. In particular, the specific effects that phytoncide or exercise provides in relation to inhibitory receptors remains to be found.
Ultimately, this study detected that aerobic exercise combined with forest bathing positively affected NK cell and NK cell related to receptors through activated epinephrine and inhibited cortisol. Moreover, this change in the immunoendocrine system in the body can be promoted a little more through exercise, and when phytoncide is incorporated, it has been confirmed that desirable changes in body composition can come through the development of cardiorespiratory endurance. However, this study has some limitations. First, the sample size consisted of only elderly men. Second, although hundreds of types of immunocytes exist, this study only observed a select portion of NK cells and related receptors. Considering these limitations, further studies investigating the effectiveness of aerobic exercise + forest bathing are encouraged to include a greater number of participants with diverse demographic backgrounds and to use multiple immunocyte tests.
This study found that aerobic exercise combined with forest bathing positively affected immunocyte function via controlled hormones in elderly men. It also found that the improved results from forest bathing + treadmill walking were caused by an increase in cardiorespiratory endurance by higher epinephrine concentrations. In addition, this increased cardiorespiratory endurance can be seen to significantly reduce body weight, fat mass, fat percentage, and BMI of the group that participated in exercise combined with phytoncide exposure.
NK, natural killer cell; NK T, natural killer T cell; NKG2D, natural-killer group 2, member D; KIR, killer cell immunoglobulin-like receptor; MHC, major histocompatibility complex; RPE, rating of perceived exertion; CON, control group; EXE, exercise group without phytoncide; PHYT, phytoncide group; EXE + PHYT, exercise + phytoncide group with phytoncide.
SP and Y-SJ conceived the idea. Y-SJ developed the background and performed the calibration of different devices used in the tests. J-KL and Y-SJ verified the methods section. All authors discussed the results and contributed to the final manuscript. SP and Y-SJ performed the tests. Y-SJ wrote the manuscript with support from SP and J-KL. All authors contributed to the final version of the manuscript. SP and Y-SJ contributed to the interpretation of the results and data analysis, and they drafted the manuscript and designed the figures and tables. All authors provided critical feedback and helped shape the research, analysis, and manuscript.
The study was conducted according to the guidelines of the Declaration of Helsinki (2013 version) and approved by the Institutional Review Board of Sahmyook University (2-1040781-AB-N-01-2017083HR) and Seoul Songdo Hospital (2021-008).
The authors wish to thank the participants of this study. And I (Yong-Seok Jee) appreciate my school and President, Ham for giving me the sabbatical year in 2021.
This research received no external funding.
The authors declare no conflict of interest. Y-SJ is serving as one of the Guest editors of this journal. We declare that Y-SJ had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to DM.
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