Safe ways to help maintain a healthy weight include reducing stress, eating healthy foods, getting enough sleep, and engaging in regular physical activity. Scientific evidence is building that sleep loss 13 can negatively affect different parts of the immune system.

This can lead to the development of a wide variety of disorders. See the recommended hours of sleep per day for your age. Smoking can make the body less successful at fighting disease. Smoking increases the risk for immune system problems, including rheumatoid arthritis.

Over time, excessive alcohol use can weaken the immune system. Taking care of yourself will help your immune system take care of you. Diet and immune function.

Accessed May 13, Western diet and the immune system: an inflammatory connection. Physical Activity Guidelines for Americans , 2nd edition [PDF Washington, DC: US Department of Health and Human Services; J Sport Health Sci.

Exercise, immunity, and illness. In: Zoladz JA, ed. Muscle and Exercise Physiology. Academic Press. T lymphopaenia in relation to body mass index and TNF—alpha in human obesity: adequate weight reduction can be corrective.

Clin Endocrinol Oxf. Changes in nutritional status impact immune cell metabolism and function. Front Immunol.

Increased risk of influenza among vaccinated adults who are obese. Int J Obes Lond. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. Hepatitis B vaccine immunoresponsiveness in adolescents: a revaccination proposal after primary vaccination. Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination.

Strengthening the immune system , since its proper functioning allows us to fight infections, detect and destroy cancer cells before they can cause damage. Decreasing the toxic load of the body by helping detoxificatio n, notably when it is genetically diminished. With this, we help to eliminate accumulated contaminants better, even using chelating substances, to be able to remove heavy metals if necessary.

Keeping tissues and cells well-oxygenated, which is essential for obtaining energy in the cells. When the cell absorbs oxygen, metabolic reactions are activated, which will generate the energy that keeps it alive.

Combatting excessive free radicals , those molecules that are so reactive and capable of irreversibly damaging the cells.

Nourishing cells adequately by providing the necessary nutrients so that they can carry out the metabolic reactions in an optimal way. More than a specialty, Revitalizing Medicine is considered a discipline within the context of Anti-Aging Medicine and with the therapeutic approach of Orthomolecular Medicine since it is dedicated to cellular rehabilitation using biochemical tools that respect cellular integrity and the internal environment.

It is fundamentally oriented towards those people who want to take care of themselves and be protagonists of their health. It is a high-speed and effective therapeutic option. The main objective of Regenerative Medicine is to optimize the vital functions to help face the day to day with more ease.

Revitalization would be the process of restoring the deteriorated functions and is quickly translated into a feeling of well-being and the recovery of mental and physical capacities. There are various therapies to carry it out. From our unit, we propose scientifically guaranteed treatments that will safely allow us to recover our biological balance, such as Ozone Therapy, Serum Therapy, and Intravenous Phototherapy.

Our recommendation is to carry out these treatments in a preventive way at least once a year and in general whenever there is fatigue or tiredness, a decrease of physical or intellectual performance, insomnia, mood alteration, or state of mind. Continued support of each award is contingent on projects meeting aggressive milestones.

The Open BAA began accepting abstracts in March and is open until March Future projects will be funded on a rolling basis. To learn more about projects as they are awarded, visit the awardee page. ARPA-H funds project to restore immune system function.

Evaluation of the changes in functional capability of Treg cells was based on in vitro functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed.

Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well.

Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages. A properly functioning immune system is essential for the continuing survival of the host by maintaining a well-balanced defense against foreign organisms and protection from endogenous altered or virally transformed cells.

However, old age inevitably leads to a number of changes that affect almost every element of the immune system and result in a progressive decline in immune functions. The mechanisms of aging involve changes in both the innate and adaptive elements of the immune system, although alterations in the adaptive arm are more well-defined.

Regarding innate immunity, we would refer to detailed and topical reviews available in this field 2 , 3. Briefly, neutrophils and macrophages show decrease in their global functions involving reduced phagocyte functions and delayed cytokine secretions, while natural killer NK cells exhibit reduced cytotoxicity and diminished migration capacity, as well.

Regarding the adaptive immunity, it has been previously observed that naïve T cells exhibit an absolute decrease with aging, which is accompanied with a relative increase in the population of various memory T cell types, primarily in effector memory T cells 4 , 5.

The changes associated with B lymphocytes are somewhat similar to the alterations observed for T cells. Naïve B cell proportion shows an age-related decrease presumably due to inadequate levels of B-cell activating factor BAFF , which is a key maintenance factor for this lineage.

On the contrary, memory B cells accumulate in older age and exhibit a more restricted repertoire of B cell antigen receptors BCR 9.

Beside the significant reduction in B cell repertoire diversity, the decreased activation and proliferative capacity of B cells can also be observed in elderly individuals thus their functional responsiveness seems to diminish with aging. Animal models revealed that aging also affects the expression of activation-induced cytidine deaminase AID , which is a key enzyme in class switching and somatic hypermutation Consequently, the decreased functional affinity avidity of antibodies in older people leads to suboptimal antibody responses and impairs the quality and efficiency of antibody-mediated immune protection.

Of note, a recent paper revealed that aging and obesity similarly impair antibody responses Interestingly, in older age, the intrinsic functional impairment of immune competence and the lack of proper immune defense are associated with a low-grade chronic systemic inflammation 12 , that may be attenuated by regular physical exercises 13 , 14 , which are also common points with the immunological characteristics of obesity Of note, studies in recent years have shown that obesity and insufficient physical activity have become a global health problem, and physical inactivity is the 4th most important risk factor for global mortality There is growing evidence that regular exercise can reduce the development and progression of a numerous chronic diseases and disabling conditions, such as cardiovascular diseases, hypertension, osteoporosis, certain cancers, cognitive impairment, dementia and depression in the elderly Regarding the immunological consequences of physical activity, regular but not strenuous exercise may increase the protective function of the immune system and reduce the risk of developing infections 18 , In contrast, high exercise training workloads are linked to immune dysfunctions and an increased risk for illness 20 , Consequently, physical activity has been shown to significantly affect immune functions; albeit, these effects seem to be highly dependent on the intensity and duration of different activities.

However, the exact mechanisms of exercise-related immunological changes are still not known in detail and only limited information is available regarding the effects of sport activities on the adaptive immune system in older ages Therefore, the aim of our study was to assess the changes in a wide spectrum of lymphocyte subtypes after a 6-week long, regularly performed, moderate-intensity functional training program in healthy elderly women.

Each volunteer completed a diet and physical questionnaire in the beginning and at the end of the study in order to assess their health condition and determine whether they comply with the criteria. Participants enrolled in the study were non-smokers, and they were abstaining from any physical exercises or sport activities, special diet and vitamin supplements for at least 3 months prior to the study.

Moreover, exclusion criteria included ongoing viral or bacterial infection, allergic or autoimmune disease, chronic disease treated with continuous drug therapy, cancer; alcohol or drug addiction, psychiatric illness, insufficient compliance and dietary changes or usage of dietary supplements during the study period, as well.

All participants attended minute long functional exercise sessions twice a week, in the morning between 8 and 9 a. for 6 weeks under stable climatic conditions 18 - 20°C at UniFit Fitness and Gym Centre in Debrecen.

All training sessions were supervised by trained instructors to minimize the risk of injury. Heart rate was monitored by the heart rate measurement system of the device. After the warm-up and aerobic sections, cyclic exercises were used to prepare the large muscles for muscle force development.

Large muscle groups of the upper, lower limbs and core muscles were trained with the help of TRX, namely, TRX squat, TRX Low Rows, TRX push up, and TRX Standing Hip Drop exercises were carried out.

Each exercise was set individually angle of inclination was set between 10° and 45° to allow the participant to execute 12 regular repetition intensively. Two participants were working together to get sufficient resting time.

To improve the balancing ability, after the TRX exercises, participants were trained with Fitball for 10 min, during the first 3 weeks with help, while in the last 3 weeks alone - without help. All training was finished with stretching section.

Table 1 summarizes the detailed training protocol. Body composition analyses were carried out by an InBody device InBody, Seoul, South Korea.

After the manual input of basic data such as height, sex and age, the measurements takes about 15 seconds. Besides the exact body weight, the analysis give a comprehensive picture on the mass of skeletal muscles and body fat regarding the whole body as well as its different parts including upper and lower extremities and trunk.

Body Mass Indexes BMI were also calculated for each measurement. Short Physical Performance Battery SPPB test was used for the evaluation of the severity of sarcopenia. SPPB evaluation includes a group of measures that combines the results of the gait speed, chair stand and balance tests The scores range from 0 worst performance to 12 best performance.

CAMRY digital hand dynamometer Camry Scale, South El Monte, CA, USA was used to measure the changes in grip strength of both hands, values were given in kilogram. For laboratory experiments, peripheral blood samples were taken baseline and 3 days after the 6-week long exercise program, in order to measure the immunological effects of the physical exercise program.

All samples were collected between and a. to avoid circadian variation. For the comprehensive phenotypic analysis of peripheral lymphocyte populations, heparinized blood samples were collected from the healthy volunteers.

The different cell populations were identified using fluorochrome-conjugated monoclonal antibodies against specific cell surface antigens. For the identification of early and late activated T cells we used CDPE-Cy5 BD Biosciences and human leukocyte antigen HLA -DR-PE Bio-Rad monoclonal antibodies, respectively, with the combination of CD3-FITC Bio-Rad.

NKT cells were identified according to the combination of 6BPE and CD3-PerCP both from BD Biosciences monoclonal antibodies. After the incubation 30 minutes, at room temperature with monoclonal antibodies, the hemolysis of erythrocytes was performed with 0.

The stained cells were assessed with Coulter FC flow cytometer Beckman Coulter and data were analyzed using Kaluza 1. The following monoclonal antibodies were used for cell surface staining: CD4-PE-Cy5 or CD8-PE-Cy5 both from Beckman Coulter. Measurements were performed and data were analyzed on Coulter FC flow cytometer Beckman Coulter equipped with Kaluza 1.

For controls and background measurements, Treg and effector Th cells were cultured separately as well. All measurements were performed in duplicate. The OD of mixed lymphocyte cultures MLR were corrected with the OD of Treg cells cultured separately as a background.

Data were analyzed with GraphPad Prism 8 software Graphpad Software, San Diego, USA. To assess the distribution of the data, Kolmogorov—Smirnov and Shapiro-Wilk normality tests were used.

In case of Gaussian distribution, two-tail paired t test was used, on the other hand, if the data set differed from normal distribution, Wilcoxon test was performed.

software Our calculation indicated that a sample size of at least 24 subjects were required to observe a statistically significant difference between matched data pairs with 0. In order to determine the effects of regular exercise on the fitness level of participants, measurements on body composition and physical performance were performed at baseline and repeated after the last exercise.

A mild significant increase was observed between the before and after values of BMI The characteristics of body composition improved, the fat mass of the body decreased significantly The participants were also able to improve their physical performance after training, since SPPB scores were significantly increased Figure 1 Measurement of physical activity in elderly women before and after the exercise training program.

A Body Mass Index BMI. B Short Physical Performance Battery SPPB index. C Mass of body fat. D Mass of skeletal muscle. E Right hand RH grip strength.

F Left hand LH grip strength. Values were calculated in kilogram kg. Wilcoxon matched pairs test was used. Each data point represents an individual subject. Bars show the mean values. Flow cytometric analyses were performed to evaluate the percentages of a wide-spectrum of immune-competent cell subsets in the peripheral blood of the participants.

According to different cell surface antigens, listed in detail in the previous section, certain lymphocyte subpopulations, including NKT cells, Treg cells as well as activated, naïve and memory cell subsets were identified. Neither total lymphocyte counts nor total NK, T and B cell numbers showed changes 3 days after the last exercise session of the workout program Supplementary Figures 1A, B.

The percentages of NK cells, T and B cells in peripheral blood did not differ significantly either Figure 2A ; however, the distribution of T and B cell subsets showed fundamental changes. The frequencies of Th cells were significantly enhanced Figure 2 The distribution of peripheral lymphocyte subsets in elderly women before and after the exercise program.

Whole blood of 29 participants were stained with fluorochrome-conjugated monoclonal antibodies as described previously.

A Representative dot plots and histograms show the gating strategy of NK, B and T cell populations. The bar chart shows the percentages of NK, B and T cells. B Representative histogram shows the gating strategy and the dot plots demonstrate the distribution of Th and Tc cells.

The bar chart indicates the frequencies of Th and Tc cells. Paired T test was used for statistical analysis. Each data point represents an individual subject, while bars show the mean values.

We found that the ratio of DN B cells was significantly decreased 4. Figure 3 Changes in the division of naïve and memory lymphocyte subsets in elderly women after the workout program. Whole blood of 29 elderly individuals were stained with labeled monoclonal antibodies as described previously.

A Representative dot plot indicates the distribution of naïve, double negative DN , switched and un-switched memory B cells. The bar chart shows the percentages of B cell subsets.

The bar chart indicates the frequencies of Th cell subpopulations. C Representative dot plot demonstrates the distribution of naïve, EMRA, CM and EM Tc cells. The bar chart indicates the frequencies of Tc cell subpopulations. Paired T test or Wilcoxon test was used for statistical analysis. Although there was no significant difference in case of naïve and memory Th cell subsets Figure 3B , a statistically significant elevation was found in the ratio of naïve Tc When we analyzed the ratio of activated T cells, we found that late-activated T cells differed significantly Furthermore, the proportions of Treg cells showed a significant decrease after the workout program 6.

Figure 4 Assessment of the changes of activated T cells, Treg cells and NKT cells in elderly women after exercise program. Whole blood of 29 elderly women were stained with labeled monoclonal antibodies as described previously.

The bar chart indicates the frequencies of activated T cells. The bar chart indicates the ratio of Treg cells. Paired T test was used. We found no significant differences in peripheral blood Th1, Th2, Th17 and Tc cells Figures 5A—C , however, the ratio of Tr1 cells was significantly diminished 0.

Figure 5 Determination of T helper and T cytotoxic cells with intracellular cytokine analysis in elderly women before and after the exercise program. Whole blood of 29 healthy participants were stimulated for 5h and dyed with fluorochrome-conjugated monoclonal antibodies with intracellular staining method as described previously.

C Ratio of IFNγ producing Tc cell. D Proportions of IL producing type-1 regulatory Tr1 cells. We measured the functional activity of Treg cells obtained from 10 healthy elderly volunteers at the baseline and at the end of the training program.

As expected, in the co-culture of MLR, the presence of Treg cells caused an obvious decrease in the proliferation, but there was no significant difference between the before and after values Figure 6B.

We found that the suppressor activity index of Treg cells did not differ significantly from the baseline values by the end of the exercise Figure 6C.

Figure 6 Suppressor activity of regulatory T cells in elderly women before and after the functional exercise program. B The bar chart indicates the proliferations of Th, Treg cells and MLR.

In the case of MLR, the Treg corrected optical density OD is displayed. C Suppressor activity index of Treg cells. Age-related changes in the immune system and their consequences became crucial issues lately, when human life expectancy keeps increasing. However, in the absence of former evolutionary pressures, the human immune system was basically not designed to function for such a long lifetime, which results in the increased susceptibility to infections and cancers in the elderly All these social and economic situation as well as individual health issues point to the urgent need to reveal effective interventions, which may delay the age-related alterations in immunity and prevent their pathological outcomes.

Appropriate and regular physical activity is a promising candidate for this purpose. Nevertheless, physical training could be a double-edged sword that can improve or even worsen immune homeostasis.

Exhaustive exercise leads to the reduction in proportions of immunocompetent cells with effector functions, as well as to a decrease of several cytokines, including IL-6, tumor necrosis factor TNF -α, IFN-γ, IL-1β, IL-2, IL-8 and IL, as well 21 , All of these deteriorating effects on immune functions may be further exacerbated by reducing the length of rest periods between the intensive physical exercises In contrast, regularly performed moderate-intensity physical activity may contribute to a reduction in the risk of cardiovascular disease and cancer by stimulating immune functions Based on the results of a previous study, physical activity may increase the number of NK cells and enhance the activity of neutrophil granulocytes in the peripheral blood 34 , Regarding the functions of the adaptive immune system, it seems that there is a significant difference between the acute impacts of single exercise bout and the effects of regular workouts.

While a single exercise bout has no clear beneficial effect on antigen-specific B cell responses to influenza and pneumococcal vaccination 36 , 37 , numerous studies demonstrated higher antibody responses to influenza vaccination in older adults, typically over 60 years of age, who regularly undertook moderate or vigorous exercise training compared to inactive controls showing that the immunological effects of regular workout may be particularly beneficial in enhancing otherwise poor responses in older age 38 , In addition to the intensity and regularity of exercise, the duration of a training session is also crucial for direction of early consequences on immune system.

In non-professional athletes, a short exercise is associated with an increase in plasma levels of anti-inflammatory cytokines such as IL-4 and IL; however, a longer exercise results in an increase of levels of pro-inflammatory cytokines such as IL-1β and TNF-α In our present study, besides examining the improvements in physical conditions, we focused on the immunological changes in healthy elderly women performing a 6-week training program with moderate-intensity.

Due to the regular physical exercises the characteristics of body composition improved, the fat mass decreased, while skeletal muscle mass increased significantly, and the latter led mild increase in BMI value.

In parallel with alteration in skeletal muscle mass, muscular strength also increased which reflects a significant improvement in the physical performance of the elderly individuals.

Importantly, changes induced by intense physical exercise may last at least 24 hours, and even moderate acute exercise induces significant immune alterations for several hours 29 , therefore we carried out the laboratory measurements 3 days after the last workout. Based on our observations, neither total lymphocyte counts nor total NK, T and B cell numbers showed any alterations 3 days after the last exercise session of the workout program indicating no distorting effects of transient immunological changes, including post-exercise lymphocytopenia.

Focusing on the distribution of naïve and memory subpopulations of B cells, we revealed that the ratio of DN B cells decreased, while percentages of un-switched memory B cells increased at the end of workout program. Of note, the generation of DN B cells seems to be a typical phenomenon due to the aging of immune system.

These cells may be exhausted memory B cells that have reverted their expression of CD27 as they have switched the heavy chain of immunoglobulin. Former studies suggest that these cells do not express HLA-DR, CD80 and CD40 which are important molecules for antigen presentation and T-B cooperation Considering the aforementioned observations, the decreased ratio of DN B cells with increased percentages of un-switched memory B cells suggest a beneficial rearrangement in the distribution of memory B cell subsets in older ages after regular exercises.

In vitro stimulation of both subset revealed that activated CD8 T cells gained more HLA-DR expression during culture Nevertheless, to get a better view on the activation state of T cells, further studies are needed on the different T subsets including naïve and memory Tc and Th cells, as well.

These results are in accordance with previous observations. It is established that this subpopulation expresses elevated β2-adrenergic receptor density and sensitivity which could explain their higher responsiveness to exercise, and it could be further augmented by cytomegalovirus seropositivity 27 , This exercise-associated shift has been reported in a recent study, in which intensive and moderate training resulted in the marked reduction of T EMRA cells, moreover they showed that the training-lifestyle was associated with telomere length preservation.

The concept is that reduced telomere erosion are associated with better immune response against infectious agents Considering that aging is associated with a decline in the number and proportion of naïve T cells, and an accumulation of memory T cells with limited specificities 4 , the applied workout intervention may be effective for the rearrangement of these cell proportions.

Although the exact mechanisms behind these anti-immunosenescence effects of regular exercise are not elucidated yet, a possible theory may answer some questions. It is assumed that the homeostatic number of peripheral T cell repertoire is tightly regulated by a negative-positive feedback mechanism that involves IL-7 and the thymus.

However, regularly executed moderate exercise might prevent immunosenescene by decreasing the accumulation of T EMRA cell clones by their mobilization into the circulation and subsequent extravasation to peripheral tissues where they are exposed to H 2 O 2 induced apoptosis.

Thereby, the negative feedback is reserved and the positive feedback increases thymic output and the accumulation of antigen-inexperienced naive T cells at the periphery 57 , Importantly, it is known that aging is associated with a predominance of Th2 cells, whereas there is a decline in Th1 cell proportions among T-helper cell population In our investigation, the exercise interventions with moderate intensity did not lead to further shift in Th1:Th2 ratios, which change would have been an adverse effect in older age.

Moreover, we did not observe any alterations in the ratios of naïve and memory Th subsets either. Based on our observations, proportions of Th subsets may hardly influenced by exercise in older ages. Regarding T cell subsets with immunoregulatory functions, it was reported that acute, high intensity exercises may cause a significant elevation in Treg cells 62 , and recently, higher levels of TGF-β, which is a known anti-inflammatory cytokine that contributes to the immunosuppressive effects of Treg cells, were also reported after workout On the contrary, a recent study reported a decrease in peripheral Treg cell numbers after regular exercises These observations shed light on the probably most important effects of physical exercises and sports on immune regulation in older ages.

Of note, at the level of adaptive immune system, the network of regulatory T cells is primarily responsible for the suppression of the effector functions of immune responses.

Although, in the regulation of peripheral T cell immune responses, several types of iTreg cells participate, its most widely investigated, key subset is the ILproducing Tr1 cell Frequencies of Treg cells also alter with age, with Treg numbers increasing 66 , 67 , which is considered to contribute to immune suppression in old age Our present findings on the effects of exercises on Treg proportions might point out the most crucial consequence of physical activity in older ages.

Additionally, beside quantitative changes, we also investigated qualitative changes in Treg cells. Based on the results of the in vitro functional tests examining the suppressor capability of Treg cells, neither enhanced nor impaired function was observed.

Taken together, the exercise-associated decrease in the proportion of Treg cells does not trigger a counter-regulatory mechanism that would lead to an enhancement in their suppressor activity. On the other hand, the lower Treg number is not accompanied with a decline of their suppressor function, which impairment would potentially increase the risk for developing autoimmune disorders or allergic diseases 65 , Our findings suggest that exercise-induced changes in the distribution of certain naïve and memory B and T cell subsets as well as in the proportions of regulatory T cells presumably indicate a retuned immune regulation and a restored responsiveness of the immune system.

Thereby, regular exercise, besides improving physical condition and age-related sarcopenia, may also delay or even reverse immunosenescence therefore can be particularly beneficial in maintaining appropriate immune functions in older ages.

Further inquiries can be directed to the corresponding author. All experiments carried out were in compliance with the Declaration of Helsinki. GP designed the study, supervised the research program, analyzed data, and wrote the main manuscript text.

KS performed laboratory experiments, analyses data, prepared figures, and contributed to manuscript writing. IJ performed laboratory experiments.

AB and AA contributed to enrolling participants and data collection. GM instructed exercise sessions. MM designed and supervised the workout program. ZC and PS contributed to the interpretation of findings and edited the manuscript.

LB provided conceptual advices and contributed to the final version of the manuscript. All authors contributed to the article and approved the submitted version. The research was supported by the GINOP The work of GP was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and the ÚNKP New National Excellence Program of the Ministry for Innovation and Technology.

AA received scholarship from the talent development program of EFOP The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol —9. doi: PubMed Abstract CrossRef Full Text Google Scholar.

Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol — Montgomery RR, Shaw AC. Paradoxical changes in innate immunity in aging: recent progress and new directions.

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Department of Phase 1 Trials Center, Harbin Medical University Cancer Hospital. Key Laboratory of Molecular Oncology of Heilongjiang Province,. K Lyu. M Zhou. J Shi. Y Guo. G Wang. T Zheng T Zheng. Address correspondence to T.

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Summary Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. Published by Oxford University Press on behalf of the Association of Physicians.

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