A Two-Way Path to Health: Exploring Whether Environmental Factors Influence Skeletal Muscle Endocrine Function and Modulate Physical Activity-Induced Adaptations in Middle-Aged Women

Poznan University of Physical Education0 个研究点目标入组 300 人开始时间: 2026年8月20日最近更新: 2026年7月15日

适应症

试验速览

阶段: 不适用
状态: 尚未招募
发起方
入组人数: 300
主要终点: Blood Cell Counts (×10⁹/L)

研究概览研究设计入排标准结局指标研究者记录与标识符相似试验

研究概览

简要总结

Given the well-established anti-inflammatory and health-promoting effects of physical activity as a non-pharmacological intervention, an important question remains whether different types of exercise differ in their ability to reduce the body burden of per- and polyfluoroalkyl substances (PFAS) and whether PFAS exposure modifies exercise-induced adaptive responses. The investigators hypothesize that the coexistence of physical inactivity, overweight/obesity, reduced muscle mass, and consequently lower concentrations of myokines/exerkines contributes to impaired cardiovascular function, reduced exercise capacity, and a greater PFAS body burden. Collectively, these factors may adversely affect work ability, reduce occupational participation, and discourage continued employment among middle-aged women. In the context of unfavorable demographic trends, such consequences may represent a significant economic burden for society.

The primary objective of this project is to determine whether baseline PFAS concentrations are associated with the health status of women entering the study and to characterize circulating profiles of myokines/exerkines and arginine metabolites. A secondary objective is to compare the effects of different exercise programs on PFAS concentrations and their potential elimination from the body. In addition, we will investigate whether a history of cancer treatment, despite increasingly favorable clinical outcomes, is associated with long-term alterations in skeletal muscle endocrine function, myokine and exerkine release, and PFAS body burden.

The study will include perimenopausal women. Participants will be allocated to one of two supervised exercise programs: high-intensity circuit training (HICT) or interval walking training (IWT). Both interventions will last six months and will be performed two times per week (with possible additional unit performed at home). This period will be followed by six months of unsupervised maintenance training. Two additional groups will be included: a control group maintaining their usual lifestyle and a group of women who have completed cancer treatment. Participants in the oncology group will be instructed to maintain a daily physical activity level of approximately 7,000-10,000 steps.

Assessments will be performed at baseline, immediately after the intervention, and six months after its completion. Circulating concentrations of selected myokines, exerkines, arginine metabolites, and 18 PFAS compounds will be measured in blood, while PFAS concentrations will also be determined in urine samples. Cardiorespiratory fitness, body composition assessed by dual-energy X-ray absorptiometry (DXA), dietary habits, quality of life, and health literacy will also be evaluated.

详细描述

To date, PFAS exposure has been linked to disturbances in lipid and cholesterol metabolism, oxidative stress, and endocrine dysfunction, including alterations in thyroid and steroid hormone regulation. However, there is a lack of data regarding the effects of PFAS-chemicals widely used in numerous industrial and consumer applications and ubiquitous in the environment-on exercise-induced adaptive responses.

Over the past two decades, research has demonstrated the critical role of specific proteins released by skeletal muscle (myokines) and other organs, including the brain, heart, and liver (collectively referred to as exerkines), in mediating physiological adaptations to exercise. The extent to which PFAS influence these signaling pathways remains unknown. The limited evidence available from animal studies suggests that PFAS may adversely affect the metabolic potential of skeletal muscle. Given the widespread presence of PFAS in the environment and their accumulation within the human body, the research proposed in this project has substantial societal and public health relevance.

Scientific evidence indicates that PFAS bioaccumulate in critical organs, including the liver, kidneys, and placenta, potentially affecting fetal development and long-term metabolic health. PFAS have been detected in multiple tissues and are characterized by prolonged biological half-lives ranging from several months to as long as six years. PFAS are known to disrupt lipid metabolism and vascular function, potentially contributing to the development of metabolic syndrome and type 2 diabetes mellitus. They have also been identified as compounds capable of altering lipid storage and energy metabolism, thereby promoting obesity. Available evidence further suggests that PFAS exposure is associated with an increased risk of cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. These adverse health effects may be amplified in urban populations exposed to high levels of environmental pollution and characterized by sedentary lifestyles with limited physical activity. Consequently, both elevated PFAS exposure and physical inactivity may independently and synergistically contribute to the burden of chronic diseases.

Given the well-established anti-inflammatory effects of physical activity and its recognized role as a non-pharmacological strategy for health promotion and rehabilitation, it is essential to determine whether PFAS accumulation limits exercise-induced adaptations and impairs the endocrine function of skeletal muscle. Recent studies suggest that environmental pollutants may influence exercise responses and PFAS clearance dynamics. However, the mechanisms regulating exercise-induced PFAS redistribution remain largely unknown. A limited number of animal studies have demonstrated potential adverse effects of PFAS on skeletal muscle cells and their regenerative capacity, whereas comparable human studies are lacking.

In recent years, myokines and exerkines have emerged as key mediators of health-promoting adaptations to exercise. Nevertheless, little is known about how persistent environmental pollutants modulate their secretion and biological activity. In our previous studies, we observed substantial interindividual variability in exercise-induced responses of several key myokines and exerkines, including interleukin-6 (IL-6), soluble IL-6 receptor, gp130, irisin, decorin, follistatin, myostatin, IL-15, N-lactoyl-phenylalanine (Lac-Phe), and brain-derived neurotrophic factor (BDNF). Given the ubiquitous presence of PFAS and their potential impact on public health, further research is urgently needed to elucidate the mechanisms of PFAS bioaccumulation, elimination, and potential mitigation strategies.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Basic Science
盲法: Single (Outcomes Assessor)

入排标准

年龄范围: 35 Years 至 75 Years（Adult, Older Adult）
性别: Female
接受健康志愿者: 是

入选标准

•(HICT, IWT and Control groups):
•aged 35-75 years
•qualified by a physician for participation in the study and with no contraindications to the training intervention (e.g., heart failure, asthma, chronic obstructive pulmonary disease [COPD], or arthritis)
•Inclusion Criteria (Onco Group):
•aged 35-75 years,
•Diagnosed with invasive breast cancer, Stage I-III disease according to the TNM classification,
•Estrogen receptor-positive (ER+) breast cancer, defined as expression in at least 10% of tumor cell nuclei,
•Adjuvant hormone therapy with an aromatase inhibitor for at least 6 months,
•BMI between 18.5 and 32 kg/m².
•Eastern Cooperative Oncology Group (ECOG) performance status of 0-
•No chronic diseases limiting the possibility of oncological treatment.
•No contraindications to daily physical activity.
•Willingness to maintain a daily step count of 8,000 steps.

排除标准

•(HICT, IWT and Control groups):
•history of cardiovascular disease,
•previous hospitalization for cardiovascular conditions,
•ongoing cardiovascular treatment, or recent cardiovascular symptoms,
•advanced osteoporosis
•Exclusion Criteria (Onco Group):
•Stage IV invasive breast cancer according to the TNM classification.
•ECOG performance status ≥
•Unstable ischemic heart disease.
•Cardiac arrhythmias.
•Advanced degenerative joint disease.
•Rheumatic disorders (including rheumatoid arthritis, osteoarthritis, or fibromyalgia).
•Progression of chronic diseases.
•Pregnancy.
•BMI <18.5 or >32 kg/m².
•Uncontrolled hypothyroidism or hyperthyroidism.