Sarcopenia is the age-related loss of skeletal muscle mass and function [1]. Due to the gradual decline in muscle mass with age, the focus of research into this disease thus far has mainly been in those over 60 years of age [1]. However, the progressive loss of skeletal muscle mass and strength begins in middle age, and evidence demonstrates that abnormal body composition is apparent before the age of 50 years [2,3]. If abnormal body composition is already present in early middle age, then implementing lifestyle interventions in younger age groups may mitigate the trajectory to low physical function, frailty, and premature death in later life. This could have important public health implications, as older people with sarcopenia are consistently reported to have lower physical function, overall health, and survival than people with normal body composition [4]. Also, low physical activity is common as people grow older [5], increasing the risk for sarcopenia [6].

Two recently published systematic reviews concluded that exercise therapy, with or without combined dietary interventions or supplementation, can be an effective treatment for older adults with sarcopenia [7,8]. However, Yoshimura et al concluded that more high-quality randomized controlled trials (RCTs) are required to confirm these results [7]. To the best of our knowledge, only 3 trials have been conducted in older adults with low muscle mass. A 10-week resistance training program was effective for maintaining functional strength and increasing muscle mass in men and women aged 70 years with low muscle mass [9]. This intervention included moderate- to high-intensity resistance training, where intensity was measured using the Borg CR10 scale, with participants rating their perceived exertion between 6 and 7 out of 10 [9]. Participants performed 8 exercises with the aim of engaging muscle groups in the whole body [9]. In another study, a 12-week multicomponent exercise program improved physical function in sarcopenic or presarcopenic individuals (≥60 years of age) [10]. The intervention consisted of resistance training, balance, flexibility, and aerobic exercises and participants determined their individual resistance load as 12 to 14 on the Borg scale [10]. Finally, a 6-month home exercise program improved physical function in 52 community-dwelling individuals (≥60 years of age) with low muscle mass or sarcopenia [11]. The home program consisted of a combination of walking (20-30 minutes per day) and lower limb resistance exercises (6× squats, 1-minute single-leg standing and 20× heel raises) [11]. To date, to our knowledge, no interventions have been conducted in middle-aged adults with low relative appendicular lean soft tissue mass.

High-intensity interval training (HIIT) was within the top 3 fitness trends for 2016 and is reported to be safe and well tolerated, with adherence that exceeds steady state training [12]. In addition to better adherence, different forms of HIIT are time efficient and provide aerobic fitness and health benefits similar to or better than traditional steady state training [12]. HIIT workouts are usually short and involve aerobic high-intensity exercises, accumulated through short bursts of activity [13]. These short bouts of activity often last between 1 and 4 minutes with a recovery phase between the bouts [13]. A metareview of 33 systematic reviews, including studies across the lifespan, showed that HIIT improved cardiorespiratory fitness, anthropometric measures, blood glucose and glycemic control, arterial compliance and vascular function, cardiac function, some inflammatory markers, and exercise capacity, and decreased heart rate (HR) and increased muscle mass compared with nonactive controls [14]. Different forms of HIIT have been proven safe in different patient populations, including cardiac rehabilitation patients [15,16] and patients with type 2 diabetes [17], rheumatoid arthritis [18], and cancer [19].

To date, to our knowledge, only a few studies have investigated the effects of HIIT on sarcopenia. A recent study in older sedentary adults demonstrated that a combination of HIIT and increased protein intake resulted in a greater increase in mitochondrial content compared with a nonexercise control group, helping to preserve oxidative capacity and slow the process of sarcopenia [20]. The protocol consisted of 5 intervals of 1 minute of stationary cycling at 85% of maximal load reached during maximum oxygen consumption (O₂max) [20]. Another study demonstrated that HIIT can improve skeletal muscle vascularization in older men [21]. The protocol as proposed by Leuchtmann et al consisted of 12 weeks of HIIT followed by 12 weeks of progressive resistance training [21]. The HIIT protocol consisted of seven 1-minute intervals of stationary cycling at 85% of the participants’ peak power [21]. The resistance training consisted of 3 sets of leg extensions, leg press, and squats with a 3-minute rest between sets [21]. After each HIIT and resistance training session, participants received a drink containing 30 g of whey protein [21]. In animal models, HIIT led to a greater muscle mass, larger muscle fiber size, and an increase in mitochondrial biomass in old, sarcopenic, and frail mice compared with nonexercise controls [22]. This research agrees with a study comparing moderate-intensity continuous training versus HIIT in middle-aged rats, showing that HIIT was better at mitigating age-related sarcopenic physiological processes such as oxidative stress and inflammation [23].

The majority of high-intensity training protocols conducted in sarcopenic individuals have been in older adults and are aerobic based. Thus, the opportunity for muscle mass development may be limited. A newer form of high-intensity training using circuit training has recently been proven effective in improving both body composition and strength measurements in middle-aged men and women (50-65 years of age) [12]. In the study by Greenlee et al, 3 center-based trainings a week with at least one day of rest between sessions for 16 weeks, improved muscle mass and muscle strength [12]. The program started with a warm-up and was followed by high-intensity cardioresistance training of 3 sets of 3 to 4 resistance training exercises followed by a set of rope jumping, 4 minutes of high-intensity cardiorespiratory exercises, and 3 sets of 2 to 4 resistance exercises [12]. These exercises were followed by 5 to 15 minutes of whole-body training and 5 to 10 minutes of yoga-inspired flexibility training [12]. HR averaged more than 80% of maximum HR throughout the sessions, and participants spent 66% of the exercise sessions between vigorous and maximal training zones [12].

Despite the positive effects of the study by Greenlee et al, to our knowledge, no high-intensity aerobic resistance training (HIART) intervention studies have been conducted in middle-aged adults with low relative lean soft tissue mass. Therefore, the primary aims of this research are to determine whether HIART can increase lean soft tissue mass and whether these changes can be maintained in the long term. Secondary aims include investigating the effect of HIART on biomarkers of sarcopenia, physical fitness, physical activity, physical function, physical activity enjoyment, self-efficacy, and adherence.

The HIIT Your Exercise Target is a single-blinded RCT testing the effectiveness of a 20-week high-intensity interval circuit training intervention on appendicular lean soft tissue mass. We obtained ethical approval for this study from The University of Otago Human Ethics Committee (H18/131) and registered it (ACTRN12618001778279). All participants will provide written informed consent in accordance with the Declaration of Helsinki. This community-based study will be conducted in the Department of Medicine, University of Otago, Dunedin, New Zealand, with training sessions carried out in the Southern District Health Board staff gymnasium, Dunedin.

We will recruit sedentary but otherwise healthy participants aged between 40 and 50 years through flyers, community webpage postings, electronic bulletin boards, and local newspapers. Interested people will be directed to complete an online screening questionnaire. Participants will be prescreened for exclusion criteria, exercise safety, and their weekly amount of physical activity. We will deem participants to be eligible to attend a screening appointment if their self-reported physical activity level is below the minimum weekly current exercise recommendations [24]; they do not take medications known to affect body composition or HR; they are not diagnosed with moderate or severe hypertension; they are not pregnant or breastfeeding, or planning on becoming pregnant during the intervention; they are not previously diagnosed with or have symptoms of cardiovascular disease or other serious medical condition; they do not weigh more than 159.9 kg (weight limit of the dual energy x-ray absorptiometry [DXA] scanner); they do not live outside of metropolitan Dunedin; and they are able to communicate in English or te Reo Māori. Further exclusion will occur for exercise safety (see the Exercise Safety Screening subsection below). Participants will receive the information sheet and will be given 2 days to decide if they are willing to participate.

Participants will undergo medical screening, as part of the screening questionnaire, to allow identification of those at high risk of an adverse event during high-intensity exercise. We will do individual medical screening, following the guidelines as proposed by the American College of Sports Medicine/American Heart Association. High-risk participants will be excluded after the online screening questionnaire. All other participants, including medium-risk participants, will be monitored with a 12-lead electrocardiogram (ECG) during the O₂max test at their first screening appointment. All ECGs will be assessed by an experienced cardiologist and require approval before the participant can enter the study.

Potentially eligible participants will attend 2 appointments as part of the screening process. During the first appointment, a blood sample will be taken, the participant will undergo a total body DXA scan to measure body composition and they will undergo a O₂max test on a stationary bicycle (see outcome measures below for more detail). At the end of the first appointment participants will receive an accelerometer (ActiGraph ) to wear for 7 days and nights to assess physical activity (see outcome measures for more detail). Participants will be emailed a weblink and will be asked to fill out several questionnaires on demographics, generic health outcomes, self-efficacy, physical activity enjoyment, and lifestyle (see outcome measures for more detail).

During the second appointment, 8 days after the first appointment, we will assess gait speed, 30-second sit-to-stand, hand grip strength, and maximal isokinetic and isometric strength of the quadriceps (see outcome measures for more detail). We will apply further exclusion criteria at this point. We will use sex-specific, height squared adjusted cutoff scores as proposed by Prado et al, to classify low appendicular lean soft tissue mass index (ALMI) measured by DXA [25]. Females with an ALMI greater than 7.72 kg/m² and males with an ALMI greater than 9.59 kg/m² will be excluded.

Figure 1 shows the study flow. Following the screening assessments eligible participants will be randomly allocated to either a control group or HIART group at a 1:1 allocation ratio. Stratified block randomization allocation sequence will be generated in REDCap (REDCap Consortium) and will be used to automatically randomly allocate participants to groups of equal sample size, stratified by sex, age and BMI. The block sizes and allocation sequence will not be disclosed to ensure concealment. The investigator collecting the data will feed data into the computer in separate datasheets, which will be anonymized by a different investigator, to ensure that all other investigators, including lab technicians, cardiologist and the primary investigators remain blinded to the treatment allocation. Statistical analysis will be performed using the anonymized datasets to ensure masking to treatment allocation.

We will conduct outcome assessments at T0 (baseline), T1 (midpoint of intervention, 10 weeks), T2 (end of intervention, 20 weeks), and T3 (end of follow-up, 40 weeks) (Figure 2).

We will assess body composition by a Lunar Prodigy DXA (Lunar Prodigy; GE Medical Systems) and analyze the results with standard software (Lunar enCORE version 16). The regions of interest for regional body composition will be defined using the software provided by the manufacturer. The scanner will be calibrated daily with phantoms for quality assurance. The laboratory coefficients of variation for repeat in vivo scans in adults in our laboratory are 1.8% for total fat mass, 1.8% for percentage fat, and 1.0% for bone-free lean tissue mass. We will measure height with a fixed stadiometer (Harpenden stadiometer; Holtain, Ltd) and weight with an electronic scale (Seca electronic scale; Seca Corp), both with participants wearing light clothing and with no shoes. Waist circumference will be measured at the top of the iliac crest, upper arm circumference will be measured halfway up the upper arm, and thigh circumference will be measured halfway up the upper leg, with nonelastic tape.

In the event of chest discomfort, failure of HR to increase normally with increased workload, light-headedness, severe fatigue, and shortness of breath, which are all abnormal responses to exercise, we will advise the participant to discontinue that exercise session. If symptoms continue for longer than 24 hours, the participant will be referred to their general practitioner. If symptoms are recurrent or take longer than 24 hours to resolve, the participant will be withdrawn from the study.

Strategies to improve adherence will include group-based participation [36], individualized exercise goals, flexibility in rescheduling to another session online, and the use of reminders. We will monitor participation adherence using attendance checklists. Adherence to the set HR goals will be monitored by recording the participants’ HR throughout the exercise sessions using HR monitors (Polar RC3; Polar Electro Oy). Adherence to the home program will be monitored with a self-reported physical activity diary.

Based on a standard deviation of 1.9 kg and an effect size f of 0.39 (obtained from previous literature [37]), our study has 95% power using a 2-sided 5% level of significance to detect clinically meaningful differences in lean soft tissue mass of 1.5 kg between the intervention and the control group with 35 participants per group. We will aim to recruit 84 participants (42 per group), which allows for 15% dropout or unusable data.

All analysis will be conducted in Stata version 15 (StataCorp LP) using the principles of intention-to-treat analysis. We will use descriptive statistics to characterize the groups at baseline. The intention-to-treat analysis for this study will include all participants, including those who are not fully compliant and those with missing outcome data. The primary outcome will be the change in total body lean soft tissue mass. Secondary outcomes include changes in physical fitness, muscle strength, physical function, and blood biomarkers. The primary analysis will compare the primary and secondary outcomes resulting from the intervention, using linear mixed models to model outcomes at T1, T2, and T3 adjusted for baseline values. Standard mixed-model diagnostics will be performed. Group differences will be presented in the form of mean differences for continuous outcomes and an odds ratio for binary outcomes, with their associated 95% confidence intervals.