Objective:Active muscle contraction is assumed to be essential in the anti-inflammatory effect of physical exercise, also in older adults. Although stretching does not involve active muscle contractions, its (anti)inflammatory effects remain unclear. This systematic review aims to determine whether stretching affects the inflammatory profile of older adults and if it can be considered as an appropriate control intervention for exercise immunology studies. Methods:This systematic review was registered in PROSPERO (CRD42023388920) and conducted in accordance with PRISMA guidelines. PubMed and Web of Science were systematically screened for articles describing the effect of muscle stretching on the inflammatory profile (immune cell proportions, cytokines, oxidative markers, and inflammatory gene expression in muscle/immune cells) in older adults. A methodological quality assessment was performed using the ROB2 tool and effect sizes (ES) were calculated. Results:Nine randomized controlled trials were included, all showing sufficient methodological quality and reporting effects on basal levels of inflammation. Muscle stretching had no effect on the number of naïve, memory, and senescence-prone T-cells or circulating inflammatory markers CRP and IL-6 neither on most studied oxidative stress markers (SOD, NO, VCAM, ICAM, PTX3, OX-LDL, MDA, HNE, nitrotyrosine, ox-LDL, and protein carbonyls). However, the oxidative stress marker LPO increased (ES=0.76) while CAT, ROS, fibrinogen, and MDA-LDL decreased (ES between -0.50 and -0.63) after stretching in older persons with chronic diseases. Contradictory results were found for TNF-alpha and gene expression levels. One study observed no changes in circulating TNF-alpha after stretching in healthy women, while another study showed an increase in muscle gene expression of TNF-alpha (ES=1.60) as well as circulating TNF-alpha (ES=0.64) in men with peripheral arterial disease. Regarding gene expression changes in pro/anti-inflammatory related genes, one study analysing RNA extracted from peripheral blood mononuclear cells showed stretching-induced increases (fold change≥1.5) or decreases (fold change≤0.67), while another study using RNA from buffy coat samples demonstrated no effect on gene expression. Conclusion:Passive or active types of muscle stretching appears to be a suitable active control for exercise immunology studies in older populations. However, in populations with peripheral artery disease with stretching may affect the inflammatory profile, possibly due to a higher overall inflammatory status.
The immunological benefits of exercise are commonly attributed to its immune-boosting effects such as the release of exercise-induced factors (e.g., exerkines) and activation of anti-inflammatory molecules. However, this may not fully explain its benefits in chronic inflammatory conditions. We propose a complementary view whereby exercise potentially functions as a biological detoxifier by removing harmful immunological debris such as damage-associated molecular patterns (DAMPs), senescent cells, dysfunctional mitochondria and pro-inflammatory extracellular vesicles (EVs) that drive chronic immune activation. We highlight key mechanisms by which exercise may reduce or remove these harmful signals, including autophagy and mitophagy activation, enhanced efferocytosis, reduced senescence burden, and modulation of EV cargo. This "immune detox" model may help explain the clinical benefits of exercise in conditions where the immune system is overactivated, not deficient. It shifts the narrative from immune boosting to restoring immune balance, and could have potentially important implications for biomarker discovery and personalized exercise prescriptions in chronic disease.
Exercise represents a non-pharmacological strategy capable of concurrently modulating tumor metabolism and immunity. Regular physical activity reprograms systemic and tumorlocalized metabolic networks, including glucose, lactate, amino acid, and lipid pathways, while enhancing innate and adaptive immune responses. Exercise-induced myokines (e.g., IL-6, IL-15, irisin, SPARC) and improved vascularization contribute to reshaping the tumor microenvironment (TME), mitigating immunosuppressive metabolite accumulation, and promoting T cell and NK cell infiltration. Mechanistically, exercise activates integrated signaling networks including AMPK-mTOR-HIF1α, PGC-1α-ERRα, and IL-6/STAT3 axes, supporting metabolic flexibility and anti-tumor immunity. Translational and clinical studies suggest exercise can enhance chemotherapy and immunotherapy efficacy, while precision exercise prescriptions based on FITT principles, biomarkers, and patient-specific tolerance may maximize therapeutic benefits. This review summarizes the molecular and systemic mechanisms of exercise-induced metabolic-immune reprogramming and outlines strategies for clinical translation in oncology.
Background:Estimating the occurrence of acute respiratory illness (ARI) in athletes is crucial for understanding the need for preventive measures. This study aimed to estimate the occurrence of ARIs in athletes compared to non-athlete controls. We evaluated which of the published studies on the occurrence of ARI in athletes were eligible, giving due consideration to the epidemic nature of viral ARIs. Methods:We performed a systematic search of PubMed, EBSCOhost, and Web of Science databases from January 1990 to May 2023. Only studies reporting the occurrence of ARIs in athletes, with a duration of at least 12 months and simultaneously employing non-athlete controls, were included. The random effects model was used to calculate the incidence rate ratio (IRR) of ARI in athletes compared to non-athlete controls, with 95% confidence intervals. Results:Our search yielded 218 results, of which 6 studies met the essential criteria for viral ARIs and were included in our metaanalysis. Since the exact number of ARIs was not reported in many studies, we had to estimate the total number of ARIs for both athletes and non-athlete controls. The occurrence of ARIs was 1.87 times higher in athletes compared to non-athlete controls (3.2 vs 1.7, pooled IRR 1.87, 95% CI 1.08 to 3.26). Publication bias analysis or a funnel plot was not evaluated because the primary objective of none of the studies was to determine the occurrence of ARI in athletes. Most of the studies on the occurrence of ARIs in athletes had a duration of less than 12 months and did not include a concurrent control group, making them ineligible considering the seasonal and contagious nature of ARIs. Conclusion:Our meta-analysis suggests that athletes suffer from significantly more ARIs than non-athletic subjects. Our observations highlighted the lack of high-quality long-term studies on the occurrence of ARIs in athletes.
Conventional chemotherapies can stimulate the immune system by increasing tumour antigenicity (e.g., neoantigen exposure to immune cells) and altering adjuvanticity in the tumour (e.g., danger associated molecular patterns and cytokines). These molecules promote the recruitment, activation, and maturation of dendritic cells, which in turn, prime and activate cytotoxic T cells against tumour cells. However, several factors can decrease the immunostimulatory efficacy of chemotherapeutic agents. These include reduced tumour cell antigenicity and adjuvanticity and compromised immune function at a local and systemic level. Findings from preclinical studies show that dietary restriction and exercise promote systemic changes that may help to restore immune system function through several mechanisms, including an enhanced infiltration and function of antitumoral immune cells and a decrease in immunosuppressive cells, leading to a reduction in tumour volume. In addition, dietary restriction and exercise training in mice have been shown to enhance the efficacy of chemotherapy. In human studies there is also emerging evidence that dietary restriction and exercise can impact the immune system towards a more antitumoral profile. In this review, we discuss the immunostimulatory effects of dietary restriction (caloric restriction and fasting) and exercise training in preclinical cancer models, and potential synergies with chemotherapy. We then review clinical studies assessing the effects of these interventions on immune-related endpoints and tumour responses. Finally, we propose that combining dietary restriction with exercise could be a promising strategy to increase chemotherapy efficacy.
