Why do People Respond Differently to Resistance Training?

It is well known that regular resistance training (RT) can have health benefits. However, considerable heterogeneity in RT responses has been observed. The mechanisms underlying an individual's ability to respond to RT are mainly unknown but involve a complex network of genomic and non-genomic factors. The investigators aim to examine heterogeneity in physiological responses to RT while closely monitoring other environmental factors (e.g., physical activity levels, nutrition, sleep, and stress). Participants are healthy sedentary males and females aged 18-50 (n=400). A controlled 12-week RT intervention will be conducted in two separate data collection periods due to our sample size to characterize RT response. Data will be collected before, during, and after the study period by using measurements of muscle size, physical fitness characteristics, and body composition, as well as by collecting blood samples and questionnaires. The investigators will identify the underlying factors contributing to why people differ in their physiological responses to RT. For this, comprehensive background data will be collected to identify common denominators underlying individual differences in response to RT. The investigators will use sophisticated analytical methods to reveal new predictors of training response for different traits. This research project aims to gain insight into the sources of individual variation in physiological responses to RT. On this basis, exercise training can be personalized to optimize the benefits of RT for all individuals. Ultimately, the investigators will also be able to justify better using RT as part of individualized healthcare strategies in the future.

The benefits of regular resistance training (RT) are well acknowledged, but it is also well known that tremendous inter-individual variability can be detected in responses to RT. The reason(s) for individual variations in responses to RT is a very complex physiological phenomenon and is still poorly known. The individual variation in trainability suggests genetic diversity, but also non-genetic determinants potentially contribute significantly to RT responses.

The investigators hypothesize that in this study, a broad spectrum of adaptive responses to RT is detected. By scrutinizing participants' backgrounds, it can be elucidated why individuals respond differently to regular RT. Furthermore, it is hypothesized that the investigators can identify specific predictive markers for RT responsiveness. That is possible by combining information on training responsiveness with the personal characteristics of the participant.

Healthy young adults aged 18-50 will be recruited to the study in two periods to understand the biological basis of heterogeneity in RT responses by minimizing potential age and health-related physiological confounders. They are premised to respond positively to the study's primary outcome, which is the cross-sectional area (CSA) of the m. vastus lateralis (VL). To collect comprehensive data, the number of participants is maximized within the practical limitations based on our previous and extensive RT studies. Therefore, of the 400 recruited participants, 240 will first undergo 12 weeks of RT (data collection I), after which 160 participants will perform an RT period with a similar design (data collection II). Thus, an RT period will be conducted in two separate periods for both of these subsamples, as 240 is the maximum number of participants that can be supervised with our comprehensive and time-consuming physiological measures within the allocated data collection timeframe. Participants comprise an equal proportion of males and females, and sex differences in RT responsiveness will be investigated as a secondary aim of the study. Combined, data collection I and II are referred to as intervention I.

The study design of the data collection I is a single-arm trial (ethical statement number 60/13.00.04.00/2023). After assessing eligibility, participants engage in the baseline measurements and the 12-week fully supervised RT intervention. Additionally, we employ a randomized dual-trial design in data collection II (ethical statement number 1394/13.00.04.00/2023) in which one arm performs a non-RT control period before an RT period, whilst the other arm only performs RT. Moreover, test-retest baseline measurements will be performed in data collection II. The RT protocol is similar for both data collections. The participants will train two times a week, and the program will target all major muscle groups. Each training session includes exercises for the lower (leg press, knee extension) and upper body (bench press, biceps curl, and seated row). The participants will perform \~10 repetitions per set (approximately 60-80% of 1RM, 8-12 RM zone) and three working sets per exercise. The last set of each exercise is performed to momentary failure in each session. Loads are increased progressively in each exercise, session to session, during the RT period using double progression based on the final set of each exercise. A questionnaire on perceived exertion after each exercise session (sRPE) will be obtained to evaluate the participant's intrinsic effort in performing exercises. The training is executed in a local university gym with a standardized time of day, and training diaries are used to track the training loads.

The measurements are obtained at baseline and after the intervention in data collection I. Furthermore, mid-measurements are also performed in data collection II. Participants are informed of the study goals and are carefully familiarized with study protocols. All the tests are carried out at the same time of day. The participants are given feedback on their test results during the project. In addition to genetics, environmental factors are essential in explaining individuality in training responses. In this project, the investigators focus on gathering comprehensive data on variables of participants' background, nutrition, health status, and physical activity that can potentially influence the heterogeneity of RT adaptations.

Eligibility Criteria:
Inclusion Criteria:

* age 18-50
* healthy (e.g., no diagnosed type 2 diabetes, cardiovascular disease, musculoskeletal disorders, etc.)
* limited experience in resistance training

Exclusion Criteria:

* medication affecting the cardiovascular system or metabolism
* metabolic, musculoskeletal, cardiovascular, or other diseases or disorders which may preclude the ability to perform exercise training and testing