A Two-Way Path to Health: Environmental Influences on Skeletal Muscle Endocrine Function

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.