Impact of aerobic exercise versus resisted exercise on endothelial activation markers and inflammatory cytokines among elderly

Background Aging is the major risk factor for the development of cardiovascular diseases as aging increases plasma levels of pro-inflammatory mediators and endothelial dysfunction. Physical exercise is a potential strategy for improving the endothelial dysfunction and chronic inflammation that accompanies aging. However, there is a need to differentiate between aerobic and resistance exercise training regarding endothelial activation markers and systemic inflammation among elderly population. Objective The aim of this study was to compare the impact of six months of aerobic versus resisted exercise training on inflammatory cytokines and endothelial activation markers among elderly. Material and methods Eighty previously sedentary elderly subjects participated in this study, their age ranged from 61–66 years. All subjects were randomly assigned to supervised aerobic exercise intervention group (group A, n=40) or resistance exercise group (group B, n=40). Results The mean value of interleukin-10 (IL-10) was significantly increased, where the mean value of inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), E-selectin, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were significantly decreased in group (A) and group (B). In addition, there were significant differences in the mean levels of the investigated parameters between group (A) and group (B) at the end of the study. Conclusion The current study provides evidence that aerobic exercise is more appropriate in modulate entering altered endothelial activation and inflammatory markers than resisted exercise among elderly population.


Introduction
Aging is associated with evident changes in the cardiovascular system that reflect alterations of biochemical adaptive mechanisms 1,2 as aging is associated with endothelial dysfunction and low systemic inflammation where the cytokines levels are usually elevated 3,4 . Inflammation is considered to have a role in disease development & prognosis 5 , and high levels of inflammatory markers in-duce an increased risk for development of cancer and cardiovascular diseases 6,7 . Aerobic exercise training may significantly lower blood pressure in older hypertensive individuals, improving endothelial function and vascular tone 8 . In particular, swimming exercise has been shown to elicit hypotensive effects and improvements in vascular function in previously sedentary older adults 9 . However, aerobic and resistance exercise can improve the functional capacity among elderly population 10,11 . Aerobic and resistance exercises training has been recommended as an anti-inflammatory therapy [12][13][14] .
It has been suggested that exercise is associated with an improvement in endothelial function, arterial wall properties and healthy status, with a parallel reduction in sys-tolic blood pressure, inflammatory process, and oxidative stress [15][16][17] . Regular aerobic exercise can slow down the age-related losses in endothelial function 18 .
As there is limitation in studies reporting the differences between the benefits of aerobic exercise and resistance exercise upon endothelial activation markers and systemic inflammation among elderly Saudi subjects. This study was an intention to compare the influence of six months of aerobic exercise and resisted exercise upon endothelial activation markers and immune system response among elderly.

Patients and methods Subjects
Eighty sedentary Saudi elderly volunteers; their age ranged from 61 to 67 year, recruited from the community. They were considered sedentary if they had not performed exercise of 15 minutes duration more than two times per week for the previous six months. Exclusion criteria included smoking, cancer, arthritis, immune disorders, taking medications that affect immune function (i.e. aspirin, anti-inflammatory drugs and anti-depressants), recent surgery, infection and vaccination. Participants were randomized to either an aerobic exercise group (group A) or resistance exercise group (group B). Both groups participated in the exercise intervention conducted three times per week for six months (starting in April-June and ending in October-December, 2017). Exercise sessions were supervised and monitored by trained exercise specialists. Infored consent was obtained from all participants. This study was approved by the Scientific Research Ethical Committee, Faculty of Applied Medical Sciences at King University.

Measurements
The following measurements were taken before the study and after six months at the end of the study. A. Inflammatory cytokines: Blood samples were drained from the antecubital vein after a 12-hour fasting, the blood samples were centrifuged at + 4 °C (1000 = g for 10 min). "Immulite 2000" immunassay analyzer (Siemens Healthcare Diagnostics, Deerfield, USA) analyzed Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels. However, tumor necrosis factor-alpha (TNF-α) was measured by ELISA kits (ELX 50) in addition to ELISA microplate reader (ELX 808; BioTek Instruments, USA); intra-assay coefficients of variation was less than 3.5% for all measurements. B. Determination of endothelial activation markers: The serum samples were stored at −80 °C to be used by the enzyme-linked immunosorbent assays (ELISAs) in order to measure levels of ICAM-1 and VCAM-1 , E-selectin, (R&D Systems).

Procedures
A. Aerobic exercise training program: Patients in group (A) were enrolled in aerobic exercise training sessions on a treadmill (the initial, 5-minute warm-up phase performed on the treadmill at a low load, each training session lasted 30 minutes and ended with 5-minute recovery and relaxation phase) either walking or running, based on heart rate, until the target heart rate was reached, according to American College of Sport Medicine guidelines. The program started with 10 minutes of stretching and was conducted using the maximal heart rate index (HRmax) estimated by 220-age. First 3 months = 60-70% of HR max , second 3 months = 70-80% of HRmax 19 . B. Resistance exercise training: Patients of group (B) were enrolled in resistance exercise training sessions. The program started with 10 minutes of stretching and was conducted with exercises done on nine resistance machines. The resistance machines used were: chest press, bicep curl, triceps extension, lower back, abdominals, leg press, leg curl and leg extension. Subjects performed three sets of 8-12 repetitions, with 60 seconds of rest between each set. Resistance was increased by five pounds after the subject was able to complete three sets of eight repetitions on three consecutive days. Subjects were trained using between 60 and 80% of their one maximal repetition weight (1-RM) 20 .

Statistical analysis
The mean values of the investigated parameters obtained before and after six months in both groups were compared using paired "t" test. Independent "t" test was used for the comparison between the two groups (P<0.05).

Results
The two groups were considered homogeneous regarding the demographic variables (figure 1). The mean age of group, (A) was 64. 28  There were no significant differences in age, weight, height, body mass index (BMI), systolic blood pressure, diastolic blood pressure and maximal heart rate (HRmax) between the two groups.

Discussion
Aging is associated with increased cardiovascular risk, systemic inflammation and endothelial dysfunction 21,22 .
To the best of our knowledge, this is the first comparative study between aerobic and resistance exercises addressing inflammatory and endothelial activation markers among elderly subjects after six months of exercise training.
Our results demonstrated that both aerobic and resistance exercise training resulted in reduction in the mean values of TNF-α, IL-6 and CRP, in addition to elevation in the mean value of IL-10 which suggested that exercise training could modulate systemic inflammation biomarkers in elderly individuals with more significant changes following aerobic exercise training. Several studies have shown that moderate physical exercise promotes the modulation of inflammation [23][24][25] . Several large cohort studies have found a relationship between self-reported physical activity levels and systemic markers of inflammation: higher levels of physical activity are coupled to lower levels of circulating inflammatory markers in elderly individuals [26][27][28] . Regarding the aerobic exercise training, our results agreed with Nicklas et al. showed that regular aerobic exercise training was efficient in lowering IL-6 levels even without weight loss 29 . While, Santos and colleagues proved that moderate aerobic exercise training for 60 min/day, 3 days/week for six months can improve sleep in the elderly via anti-inflammatory effect of aerobic training 30 . However, Kohut et al. reported that 10-months of aerobic, but not resistance exercise, significantly reduced serum inflammatory mediators in older adults 31  Our results demonstrated that aerobic exercise training resulted in greater significant reduction in the mean values of ICAM-1, VCAM-1 and E-selectin than resistance exercise training. These findings agreed with Yang and colleagues investigated exercise effects on the vascular function in hypercholesterolemia, male New Zealand white rabbits proved that animals of exercise groups who ran on a treadmill at 0.88 km/h for 10-60 min/day, 5 day/ week, and 8 weeks in total resulted in reduction in the expression of adhesion molecules and ameliorates the severe vascular dysfunction induced by high cholesterol feeding 40 . While, Zoppini and colleagues proved that a twice-weekly, 6-month, progressive aerobic-training program, without a concomitant weight loss diet, is associated with significant decreases in circulating P-selectin and ICAM-1 levels (P<0.01) and with a less atherogenic lipid profile in addition to significant increase in level of HDL cholesterol by 12% (P<0.05) and decreased uric acid levels by approximately 33% (P=0.021) in overweight, non-smoking, older type 2 diabetic individuals 41 . However, Jilma and colleagues stated that after two different training protocols on an bicycle ergometer and endurance exercise in healthy untrained men at normal altitude have little influence on serum levels of the circulating vascular adhesion molecules 42 . Moreover, Link and colleagues investigated the systemic effect of physical training on the lower limbs, on the endothelial function of the radial artery in 22 men with congestive heart failure after one month, when compared to the control group 43 . Similarly, Payvandi and co-workers stated that increased levels of physical activity during daily life are associated with improved endothelial function in patients with peripheral arterial disease 44 .
The current study has important strengths and limitations. The major strength is the supervised nature of the study as all exercise sessions were supervised. In the other hand, the major limitations is only elderly subjects enrolled in the study, so the value of this study only related to this age group, also small sample size in the two groups may limit the possibility of generalization of the findings in the present study. Finally, within the limit of this study, aerobic exercise is more appropriate than resisted exercise in modulation of inflammatory and endothelial activation markers among elderly. Further researches are needed to explore the impact of exercise training on quality of life and other biochemical parameters among elderly.