Acute Inflammatory Response to Eccentric Exercise in Young and Master Resistance-trained Athletes.

This study aimed to compare the acute inflammatory response following high-intensity eccentric exercise between resistance-trained young and master athletes with similar performance levels. Resistance-trained young (n=8; 22±2 years) and master (n=8; 52±4 years) male athletes of a similar performance level performed a standardized high-intensity eccentric squat exercise protocol (10 sets of half-squats at 70% of 1-repetition maximum). The serum concentration of 20 biomarkers related to tissue damage, inflammation, remodeling, and repair was measured at baseline, immediately after exercise, and over a 72 h recovery period. Both groups experienced similar muscle damage as evidenced by a comparable increase in creatine kinase activity 24 h after exercise (p<0.001). Interleukin-6 (p=0.009) and growth hormone (p<0.001) increased immediately post-exercise in both groups. Monocyte chemoattractant protein-1 increased immediately post-exercise only in young athletes (p=0.003) and then decreased 24 h later. There were no significant differences for the remaining variables, including cell markers related to neutrophil/macrophage activation or pro/anti-inflammatory cytokines. Resistance-trained young and master athletes, matched for performance level, showed an overall similar inflammatory response to eccentric exercise, possibly reflecting regulatory mechanisms or immunological adaptations to chronic stimulation in master athletes.

Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study.

OBJECTIVE: To investigate the role of central obesity on immunometabolic response in peripheral blood mononuclear cells (PBMCs) from normal weight and overweight/obese young men. METHODS: Eighteen individuals were classified as normal weight (NW; n = 9 - age: 25 ± 5 and BMI: 21.4 ± 1.7) and overweight/obese (OW; n = 9 - age: 29 ± 7 and BMI: 29.2 ± 2.7). The body composition was evaluated by dual-energy x-ray absorptiometry (DXA), waist circumference, and visceral and subcutaneous fat depots by ultrasound. Physical activity levels, metabolic parameters, immune phenotypic characterization, cytokine production by lipopolysaccharide (LPS) -stimulated whole blood cells and LPS or phorbol 12-myristate 13-acetate (PMA)-stimulated PBMC, and mitochondrial respiration in PBMCs were evaluated. Expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR-4), hypoxia-inducible factor-1 alpha (HIF-1α), and adrenergic receptor beta 1 and 2 (AR-ß1 and ß2) genes were evaluated in cultured PBMC using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Individuals with overweight/obese (OW) presented higher glucose (P = 0.009) and leptin (P = 0.010) than individuals with normal weight (NW). PBMCs of OW under stimulation with LPS presented a lower production of interleukin-10 (IL-10) (P = 0.011) and macrophage inflammatory protein-1alpha (MIP-1α) (P = 0.048) than NW. Mitochondrial respiration rates were not different between NW and OW subjects. Cultured PBMCs in LPS-stimulated condition indicated higher gene expression of AR-ß2 in OW, while PMA-stimulated PBMCs presented lower expression of AMPK (P = 0.002) and higher expression of NF-κB (P=<0.0001) than NW. OW presented higher numbers of CD3+CD4+ T cells (P = 0.009) and higher expression of programmed cell death protein 1 (PD-1) in CD8+ T cells (P = 0.001) than NW. CONCLUSION: Central obesity promoted reductions in interleukin 10 production response and increase in AR-ß2 expressions in mitogen-stimulated PBMCs. Furthermore, central obesity altered the phenotype of PBMCs, also increasing the expression of PD-1 exhaustion markers in young adults.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Autophagy of naïve CD4+ T cells in aging - the role of body adiposity and physical fitness.

Life expectancy has increased exponentially in the last century accompanied by disability, poor quality of life, and all-cause mortality in older age due to the high prevalence of obesity and physical inactivity in older people. Biologically, the aging process reduces the cell's metabolic and functional efficiency, and disrupts the cell's anabolic and catabolic homeostasis, predisposing older people to many dysfunctional conditions such as cardiovascular disease, neurodegenerative disorders, cancer, and diabetes. In the immune system, aging also alters cells' metabolic and functional efficiency, a process known as 'immunosenescence', where cells become more broadly inflammatory and their functionality is altered. Notably, autophagy, the conserved and important cellular process that maintains the cell's efficiency and functional homeostasis may protect the immune system from age-associated dysfunctional changes by regulating cell death in activated CD4+ T cells. This regulatory process increases the delivery of the dysfunctional cytoplasmic material to lysosomal degradation while increasing cytokine production, proliferation, and differentiation of CD4+ T cell-mediated immune responses. Poor proliferation and diminished responsiveness to cytokines appear to be ubiquitous features of aged T cells and may explain the delayed peak in T cell expansion and cytotoxic activity commonly observed in the 'immunosenescence' phenotype in the elderly. On the other hand, physical exercise stimulates the expression of crucial nutrient sensors and inhibits the mechanistic target of the rapamycin (mTOR) signaling cascade which increases autophagic activity in cells. Therefore, in this perspective review, we will first contextualize the overall view of the autophagy process and then, we will discuss how body adiposity and physical fitness may counteract autophagy in naïve CD4+ T cells in aging.

Exercise training-induced changes in immunometabolic markers in youth badminton athletes.

The aim of this study was to investigate the metabolic and inflammatory fluctuations in two seasonal phases of badminton training, and the ability of youth badminton athletes to respond to an inflammatory challenge given by acute exercise on these markers. Thirteen youth badminton athletes who participated in national and international competitions were recruited. Metabolic and cytokine profile were measured at rest and in response to a maximal exercise intermittent test, in the pre- and final phases of a badminton annual season. At rest, glucose (-7.58 mg/dL; p = 0.045) and HDL-cholesterol (HDL-c) (-26.87 mg/dL; p < 0.0001) decreased at final-season. The variation of HDL-c in response to a maximal exercise test increased at final-season in comparison to pre-season (+ 10.20 mg/dL p = 0.042). Similarly, delta changes of IL-10 (+ 3.41 pg/ml; p = 0.047) and IL-1Ra (+ 141.3 pg/ml; p = 0.031) were greater at final-season. In addition, a significantly greater variation of the anti-inflammatory IL-10/IL-17 ratio was observed at final-season (+ 0.37; p = 0.010). In conclusion, our results showed a major responsivity of IL-10 and IL-1Ra to a maximal exercise even at the end of an entire season. The major responsivity of these cytokines at this time point suggests a more effective acute inflammatory response in youth badminton athletes. Therefore, the results of this study may be applied by coaches, trainers and sport nutritionist for proper training management.

The growing field of immunometabolism and exercise: Key findings in the last 5 years.

This perspective review highlights the impact of physical exercise on immunometabolic responses in the past 5 years. Understanding immunometabolism as a part of immunological research is essential. Furthermore, the roles of both acute and chronic effects of physical exercise on health, aging, and chronic diseases in immunometabolic changes should be elaborated. In immune cells, ß2 adrenergic signaling stimulates the preferential mobilization of inflammatory phenotypes, such as CD16+ monocytes and CD8+ T cells, into the bloodstream after a physical exercise session. The mobilization of immune cells is closely related to the availability of energetic substrates for the cell and mechanisms associated with the uptake and oxidation of fatty acids and glucose. These cells, especially senescent T cells, are mobilized to the peripheral tissues and undergo apoptotic signaling, stimulating the creation of a "vacant space" where new cells will be matured and replaced in the circulation. This results in the upregulation of the expression and secretion of anti-inflammatory cytokines (IL-10 and IL-1ra), leading to increased regulatory immune cells that provide immunoregulatory properties. Thus, we suggest that a significant nutrient available to the cell will favor oxidative metabolism, augment ATP production, and consequently maintain the immune cells in their quiescent state, as well as promote rapid activation function. Therefore, based on the studies discussed in this perspective review, we highlight the importance of performing moderate-intensity continuous and high-intensity intermittent aerobic exercises, due to a higher magnitude of energetic demand and release of anti-inflammatory cytokines (IL-6 and IL-10).

Feeding Pattern, Circadian Rhythm, and Immune Function: What do we know about?

Feeding pattern is related to health status or chronic diseases, and this depends on the individual's eating habits. Feeding organized with the right time to start and end during the day, promotes an internal biological rhythm, favoring molecular synchronization of the clock genes, which impose an effect on metabolism and immune cells, creating a physiological response related to a healthy profile. On the other hand, a feeding pattern disorganized, without the right time to start and end eating during the day, might lead to nonsynchronization of the clock genes, a disruption condition, which is related to chronic diseases, such as obesity and diabetes type 2. A strategy that should be adopted to favor molecular synchronization is time-restricted eating (TRE), which can organize the initial and end of the eating patterns during the day. Our review points out some cues that suggest TRE as an efficient strategy for healthy profile and can be a good intervention for the treatment of chronic diseases.

Immunometabolism-fit: How exercise and training can modify T cell and macrophage metabolism in health and disease.

BACKGROUND: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally. SCOPE OF REVIEW: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society. MAJOR CONCLUSIONS: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.

Costly immunometabolic remodelling in disused muscle buildup through physical exercise.

The mechanisms underlying the immunometabolic disturbances during skeletal muscle atrophy caused by a plethora of circumstances ranging from hospitalization to spaceflight missions remain unknown. Here, we outline the possible pathways that might be dysregulated in such conditions and assess the potential of physical exercise to mitigate and promote the recovery of muscle morphology, metabolism and function after intervals of disuse. Studies applying exercise to attenuate disuse-induced muscle atrophy have shown a pivotal role of circulating myokines in the activation of anabolic signalling pathways. These muscle-derived factors induce accretion of contractile proteins in the myofibers, and at the same time decrease protein breakdown and loss. Regular exercise plays a crucial role in re-establishing adequate immunometabolism and increasing the migration and presence in the muscle of macrophages with an anti-inflammatory phenotype (M2) and T regulatory cells (Tregs) after disease-induced muscle loss. Additionally, the switch in metabolic pathways (glycolysis to oxidative phosphorylation [OXPHOS]) is important for achieving rapid metabolic homeostasis during muscle regeneration. In this review, we discuss the molecular aspects of the immunometabolic response elicited by exercise during skeletal muscle regeneration. There is not, nevertheless, consensus on a single optimal intensity of exercise required to improve muscle strength, mass and functional capacity owing to the wide range of exercise protocols studied so far. Despite the absence of agreement on the specific strategy, physical exercise appears as a powerful complementary strategy to attenuate the harmful effects of muscle disuse in different scenarios.

Type and Intensity as Key Variable of Exercise in Metainflammation Diseases: A Review.

Monocyte and lymphocyte subpopulations exhibit functions that vary between the anti- and pro-inflammatory spectrum, such as classic CD16- and non-classical CD16+monocytes, as well as T helper 2 lymphocytes (Th2), the Th1/Th17 lymphocytes ratio, and T regulatory lymphocytes (Treg). Metabolic disease-associated inflammation is accompanied by an imbalance in monocyte and lymphocyte phenotypes and functionality, as well as a stronger proportion of inflammatory subpopulations. These changes appear to be important for the development and progression of diseases like diabetes and cardiovascular disease. On the other hand, the regular practice of physical exercise is an important tool to restore the functionality of monocytes and lymphocytes, and to balance the subtypes ratio. However, key variables regarding exercise prescription, such as the type of exercise, intensity, and volume differentially impact on the acute and chronic immune response in individuals diagnosed with meta-inflammation diseases. Here, we discuss the impact of different physical exercise protocols, acutely and chronically, on monocytes and lymphocytes of individuals with metabolic disease-associated inflammation. In this review, we focus on the best effects of different exercise protocols to dose the "exercise pill" in different inflammatory status.

Modulatory Effects of Physical Activity Levels on Immune Responses and General Clinical Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections-A Protocol for an Observational Prospective Follow-Up Investigation: Fit-COVID-19 Study.

Background: This proposal aims to explain some of the gaps in scientific knowledge on the natural history of coronavirus disease (COVID-19), with a specific focus on immune, inflammatory, and metabolic markers, in parallel with temporal assessment of clinical and mental health in patients with COVID-19. The study will explore the temporal modulatory effects of physical activity and body composition on individual trajectories. This approach will provide a better understanding of the survival mechanisms provided by the immunomodulatory role of physical fitness. Methods: We will conduct a prospective observational cohort study including adult patients previously infected with the SARS-CoV-2 virus who have expressed a mild to moderate COVID-19 infection. Procedures will be conducted for all participants at baseline, six weeks after vaccination, and again at 12 months. At each visit, a venous blood sample will be collected for immune phenotypic characterization and biochemistry assays (inflammatory and metabolic parameters). Also, body composition, physical activity level, cardiovascular and pulmonary function, peripheral and respiratory muscle strength, functional exercise capacity, and mental health will be evaluated. Using the baseline information, participants will be grouped based on physical activity levels (sedentary versus active), body composition (normal weight versus overweight or obese), and SARS-CoV-2 status (positive versus negative). A sub-study will provide mechanistic evidence using an in-vitro assay based on well-trained individuals and age-matched sedentary controls who are negative for SARS-CoV-2 infection. Whole blood will be stimulated using recombinant human coronavirus to determine the cytokine profile. Peripheral blood mononuclear cells (PBMCs) from healthy well-trained participants will be collected and treated with homologous serum (from the main study; samples collected before and after the vaccine) and recombinant coronavirus (inactive virus). The metabolism of PBMCs will be analyzed using Respirometry (Seahorse). Data will be analyzed using multilevel repeated-measures ANOVA. Conclusions: The data generated will help us answer three main questions: (1) Does the innate immune system of physically active individuals respond better to viral infections compared with that of sedentary people? (2) which functional and metabolic mechanisms explain the differences in responses in participants with different physical fitness levels? and (3) do these mechanisms have long-term positive modulatory effects on mental and cardiovascular health? Trial registration number: Brazilian Registry of Clinical Trials: RBR-5dqvkv3. Registered on 21 September 2021.

COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease. Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines. Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status. Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

Levels of cardiorespiratory fitness in men exerts strong impact on lymphocyte function after mitogen stimulation.

Relationship between lymphocyte function and cardiorespiratory fitness (CRF) is well-documented at rest; however, upon mitogen stimulation the proliferation and cytokine production alters, but knowledge is incipient about lymphocyte responses after mitogen stimulus according to CRF. So, the purpose of the present study was to analyze the lymphocyte function according to the physical fitness status of healthy young men. The study is divided in two experiments being the first analyzing the lymphocyte phenotypes profile and the inflammatory responses, according to CRF, in lymphocyte cell cultures treated for 48 h with concanavalin A (ConA). The second experiment analyzed the proliferation, reactive oxygen species production, viability, and mitochondrial polarization state in lymphocytes treated with ConA in different concentrations, considering the CRF levels. The results showed a difference in the percentage of total lymphocytes expression between groups (P = 0.011) observing a lower lymphocytes T expression in the group with high maximal oxygen consumption (V̇o2max) when compared with the moderate V̇o2max group. When treated with ConA, the lymphocytes of the low V̇o2max group released higher TNF-α concentration (P = 0.032), reflecting an elevated TNF-α/IL-10 ratio (P = 0.055), parallel with lower IL-6 production (P = 0.027), mainly when compared with the moderate V̇o2max group. In addition, there is a positive relationship between V̇o2max and IL-6 production (r = 0.507; P = 0.016), whereas the percentage of total lymphocytes (LyT%) shows a negative trend with V̇o2max (r = -0.497; P = 0.060). Also, individuals with lower V̇o2max showed reduced absolute and relative ROS production, lower cell proliferation, and higher mitochondrial membrane depolarization. In conclusion, cardiorespiratory fitness degree exerts a strong impact on lymphocyte function after mitogen stimulation.NEW & NOTEWORTHY The innovation of the research is to elucidate the impact of different physical fitness status on metabolism, cell proliferation, and lymphocyte activity and, consequently, on the specific inflammatory response against a mitogen.

Probiotic supplementation in marathonists and its impact on lymphocyte population and function after a marathon: a randomized placebo-controlled double-blind study.

Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10 × 109) and Lactobacillus-Acidophilus (10 × 109) + 5 g of maltodextrin) and placebo (5 g of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood were collected 30 days before (rest), 1 day before (pre), 1 h after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation.

Inflammatory features of obesity and smoke exposure and the immunologic effects of exercise.

Many lifestyle-related diseases, such as obesity and cigarette smoke-induced pulmonary diseases, are associated with chronic systemic inflammation, which has been shown to contribute to the disease initiation and progression, and also for co-morbidities of these diseases. While the source of inflammation in obese subjects is suggested to be mainly the visceral adipose tissue, smoke-induced inflammation originates in the pulmonary system. Here, chronic cigarette smoking induces oxidative stress, resulting in severe cellular damage. During obesity, metabolic stress pathways in adipocytes induce inflammatory cascades which are also accompanied by fibrotic processes and insulin resistance. In both diseases, local inflammatory signals induce progressive immune cell infiltration, release of cytokines and a subsequent spill-over of inflammation to the systemic circulation. Exercise training represents an effective therapeutic and immune regulating strategy for both obese patients, as well as for patients with smoke induced pulmonary inflammation. While the immuneregulating impact of exercise might primarily depend on the disease state, patients with pulmonary inflammation seem to be less responsive to exercise therapy. The current review tries to identify similarities and differences between inflammatory processes, and the consequences for the immunoregulatory effects of exercise as a therapeutic agent.

Regulation of autophagy as a therapy for immunosenescence-driven cancer and neurodegenerative diseases: The role of exercise.

Aging is one of the risk factors for the development of low-grade inflammation morbidities, such as several types of cancer and neurodegenerative diseases, due to changes in the metabolism, hormonal secretion, and immunosenescence. The senescence of the immune system leads to improper control of infections and tissue damage increasing age-related diseases. One of the mechanisms that maintain cellular homeostasis is autophagy, a cell-survival mechanism, and it has been proposed as one of the most powerful antiaging therapies. Regular exercise can reestablish autophagy, probably through AMP-activated protein kinase activation, and help in reducing the age-related senescence diseases. Therefore, in this study, we discuss the effects of exercise training in immunosenescence and autophagy, preventing the two main age-related disease, cancer and neurodegeneration.