Aging leads to declines in functional capacity and effort tolerance. Muscle strength remains stable from ages 25 to 50 but declines significantly after age 60, affecting activities like stair climbing and walking, reducing autonomy and independence. While muscle atrophy is a significant factor, macrovascular endothelial dysfunction also impairs skeletal muscle performance in older adults. Nitric oxide (NO), produced by endothelial cells, regulates vascular homeostasis and contractile function. NO enhances muscle fiber shortening velocity, reduces twitch time-to-peak contraction, and increases the rate of force development. Aging-related endothelial dysfunction reduces NO availability, leading to reduced muscle mass and sarcopenia via decreased skeletal muscle perfusion. Increased arterial stiffness disrupts ventricular-vascular coupling, reducing cardiac output and contributing to age-related muscle weakness. Additionally, microvascular function decreases with age, contributing to altered physical work perception and reduced function. Low capillary density is linked to reduced walking speed in older adults and reduced walking time in peripheral arterial disease patients, supporting the microvasculature's role in functional performance. Reduced muscle mass also increases central hemodynamic load, impacting arterial stiffness and cardiac function.

Resistance training (RT) is recommended to mitigate aging effects like loss of strength and muscle mass and reduce cardiovascular risk and all-cause mortality. Guidelines suggest 1-3 sets of 8-12 repetitions at 60-80% of the individual's repetition maximum (1RM), performed at least twice a week. However, older adults with osteoarthritis and cardiovascular conditions often cannot tolerate high mechanical stress and are prescribed lower intensity-resistance training (LIRT) at 40-50% of 1RM, typically yielding negligible muscle hypertrophy or strength gains. Blood flow restriction (BFR) training, which applies pressure bands to restrict blood flow during LIRT, increases muscle volume and strength. While BFR shows promise, it can cause acute increases in arterial stiffness and blood pressure in older adults, necessitating caution in its prescription.

This study aims to compare macrovascular and microvascular function responses to acute resistance exercise with and without BFR in young and older adults. We hypothesize that older adults will show a more pronounced increase in macrovascular and microvascular dysfunction following resistance exercise compared to younger participants. In this parallel group randomized controlled trial, participants will be randomly assigned to either LIRT-BFR or high-intensity resistance training (HIRT). Each participant will attend three sessions: a familiarization session and two experimental sessions involving the randomized exercise conditions. Measurements of brachial blood pressure, heart rate, and macrovascular and microvascular function will be taken at rest and during recovery periods post-exercise.

In this parallel group crossover randomized trial, young and older adults participants will be randomly assigned to 2 experimental conditions: a LIRT+BFR and HIRT. These two conditions were chosen because acute LIRE+BFR and HIRE have been shown to increase similarly heart rate and blood pressure in older adults. Each participant will report to the Laboratory on 3 occasions, at least 1 week apart. In visit 1, participants will have their body weight and height measured, and be evaluated twice for macro- and microvascular function within 30 min at resting condition (control). After that, they will become acquainted with the exercise protocol and determine their one-repetition maximum (1RM) for the bilateral leg press exercise and knee extension. In visits 2 and 3, participants will perform the experimental conditions in a simple randomized order, to which participants will be blinded until arrival at the laboratory.

The allocation sequence will be generated by Dr. XM, using a web-generated simple randomization scheme (http://www.randomizer.org/), and placed in sequentially numbered, opaque, sealed envelopes to ensure concealment of the allocation process and minimize potential biases to researchers and participants, delivered to field researchers, who will be blind, on the day of the first visit.

Each session will begin with 15 minutes of supine rest on a cushioned examination table. This will be followed by: 1) assessment of brachial blood pressure, heart rate and microvascular function at rest as measured by finger photoplethysmography (Vicorder, Berlin, Germany). Following these assessments, participants will engage in one of the previously randomized resistance training experimental conditions for roughly 30 min. After that, participants immediately return to the examination table and will recover in the supine position for 30 minutes, during which brachial blood pressure, heart rate and microvascular function will be re-evaluated 5-, 30-min intervals into recovery and compared to those at rest. Post-exercise time measurements are aimed to characterize the post-exercise biphasic response of the microvascular function.

Participants will be instructed to avoid caffeine and alcohol for 24 hours, and fully void before the session. They will also be advised to avoid vigorous exercise-related activities 24 hours before each session, including the familiarization session. All evaluations will be led by 4 physiotherapy students per participant (4:1), with over 30h of training in the evaluation and training protocols. During the participant's time in the laboratory, a certified professional in basic life support and automated external defibrillators (AEDs), will be present at the clinic.

Based upon an effect size of 0.141 derived from the mean and dispersion response of carotid-radial pulse wave velocity to Non-Autoregulated Blood Flow Restriction resistance exercise. 48 participants are required, (24 per group), matched for sex, assuming a 5% alpha error, and 20% beta error, with a 1:1 ratio between groups. To account for a 10% dropout rate, a total of 52 will be recruited.

Young adults at Egas Moniz School of Health & Science will be recruited through Instagram ads and strategically placed posters. Interested individuals will use a QR code to access a form with study details and eligibility criteria. Eligible participants will receive an electronic informed consent form to sign before their first visit. Older adults will be recruited from local senior centers, gyms, and community programs via email. Those who meet the eligibility criteria will receive a printed informed consent form to sign before their first clinic visit.

Inclusion Criteria:

• Aged between 18-30 years and those over 60 years.

Exclusion Criteria:

• Past or current history of coronary heart disease, stroke, oncological disease, or major cardiovascular events.
• Individuals who had undergone surgery within the last two months
• Body mass index (BMI) greater than 30 kg/m²
• Declared sleep apnea
• Active kidney or liver disease
• Active tobacco smokers
• Sensory impairments
• Neurological or orthopedic functional impairments, musculoskeletal pathologies affecting exercise capacity
• Physically active for more than six months with a weekly activity level of 1,000 MET/min.

Data obtained in this study may be provided to qualified researchers with academic interest in vascular responses to resistance training with blood flow restriction. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact xmelo@egasmoniz.edu.pt

Outcomes will be assessed by the same experts in every time point. Participants and evaluators will be blinded until arrival of the participant for the fist experimental condition.