Visit 1 (1 hour): Paperwork and Anthropometrics

Upon arriving at the Human Testing Center at the University of Massachusetts-Amherst, you will be asked to read this Informed Consent document. During the first visit, laboratory personnel will review the informed consent document with you and answer questions. Once consenting is complete, you will be asked to fill out the study questionnaires (PAR-Q+, Health History Questionnaire and MR Safety Screening Questionnaire), sign a release form allowing us to send a letter to your personal physician clearing you to participate in the study, and fill out a University of Massachusetts W-9 and a Photo Release Form. After you complete this paperwork, we will measure your height, body mass, blood pressure and heart rate. Lastly, you will be issued an activity monitor and provided with instructions on how to wear it and fill out activity logs for a period of 7 days

Visit 2 (3-4 hours): Body Composition, Blood Draw and Muscle Biopsy

During your second visit, we will measure your body composition using MRI and dual-energy X-ray absorptiometry (DEXA). Both of these tests will determine the quantity of muscle and fat in your body. We will measure the composition of your thigh with MRI. Before entering the magnet room, we will review your MR Safety Screening Questionnaire and have you remove all jewelry. We will then scan you for metal using a hand-held metal detector. Next, you will be escorted into the Magnet Room, where you will be positioned in the scanner on your back, with your head on a pillow and your arms resting comfortably at your side. We will lay a mat or circular coil on one of your thighs and slide you into the center of the magnet. This mat/coil will be used to obtain images of your thigh muscles. This will take about 20 minutes. We will then remove you from the magnet and place the mat/coil on your other leg. We’ll then move you back into the magnet and repeat the MRI scans; this process will also take approximately 20 minutes. It will be important that you not move during the scanning. For the measures of both thighs, we will use Velcro straps to secure your feet so that you do not move in the event that you fall asleep during the study. Headphones will be provided to you to limit the amount of noise from the scanner, and to enable clear and constant communication between you and the investigators. We will talk with you and let you know when each set of measures will begin, and how long they will take. We will also measure your overall body composition using a DEXA scan. For this test, you will lie on an examination table while the machine scans your entire body with a low-level X-ray. The measurement takes approximately 10 to 15 minutes depending on your height and weight.

You will also be asked to undergo a blood draw (to examine testosterone and dihydrotestosterone levels in men and estradiol levels in women) of 30 ml (~2 tablespoons) and biopsies of the thigh muscle from your right and left legs. You need to be fasted (no food, but you can drink as much water as you like) for at least 8 hours before both of these procedures. The biopsy procedure allows us to obtain muscle tissue to test the function of the individual fibers that make up your muscles (muscle fibers are ‘cells’ that make up your muscles). Because we expect the function of your muscle fibers to change as a result of the exercise training, it is necessary to perform a biopsy at baseline and then after you complete the exercise program. However, because you will be performing different types of resistance training exercise with your left and right legs, it is necessary for us to test the function of muscle fibers from each leg to determine if they are different. For example, if your left leg is assigned to traditional resistance training and your right leg is assigned to power training, we want to determine how the function of muscle fibers in each leg changes following the programs. The details of the muscle biopsy are described below.

You will be instructed not to consume any anti-inflammatory drugs (i.e. Ibuprofen or aspirin) or any aspirin-containing drugs such as Alka-Seltzer, Pepto-Bismol, or certain decongestants that contain anti-inflammatory drugs (i.e. Dristan) within 4 days of the muscle biopsy to reduce risk of bleeding. You will be given a telephone number that may be used to reach the Muscle Biology Laboratory. If you areunsure as to whether a medication you intend to take contains aspirin, it is strongly advised that you call one of the study investigators before taking the medication.

A trained physician will perform the needle biopsy procedure, which involves the removal and examination of a piece of muscle tissue. The muscle biopsy will be obtained under local anesthesia. A small incision (about 1 cm) is made into the skin and fascia. To take a biopsy, a needle is then inserted into the muscle. A small "plug" of tissue remains in the needle when it is removed from the muscle. This is about the size of 2-3 grains of rice. More than one needle insertion may be needed to obtain a large enough specimen for testing and examination.

The muscle that we will biopsy is the outer thigh muscle at a location of about mid-way between the knee and hip. You will feel some pressure or "tugging" sensations. Many people experience mild discomfort, but some subjects find the biopsy procedure painful. If there is pain, the physician will provide more anesthetic to the area to reduce the pain. The anesthetic is called Lidocaine (like Novocaine) and may burn or sting when injected (before the area becomes numb). After the anesthetic wears off, the area may be sore or painful for a day or two and may limit your activity. The post-biopsy sensation has been compared to what your leg feels like after hitting your thigh against a table top when walking past. Occasionally, muscle soreness lasts longer, but in these cases is typically gone within 7 days of the biopsy. The incision site takes time to heal, several days to a week, so must be cared for, similar to a cut, using written instructions we will provide you after the biopsy. The risks associated with biopsies are small and include the following: infection (a slight risk any time the skin is broken), hematoma (blood collected beneath the skin that under very rare conditions could require surgery), bruising of the area, and damage to the muscle tissue or other tissues in the area (very rare). These risks are very low because there are no big blood vessels near the biopsy site and because the muscle tissue usually stops any bleeding by pressing against itself. Also, studies have shown that the muscle rapidly repairs itself after the biopsy. It is possible that you may have temporary numbness around the biopsy site for several days to weeks. At the biopsy site, a small scar about 1 cm long or less could result, but usually this will fade in time. Risks are minimized by having a trained and qualified medical physician perform the biopsy using sterile equipment.

Visit 3 (45 minutes): Biopsy Sites Check and Dynamometer Familiarization

Three to four days after your biopsies, you will come to the Human Testing Center so we can check your biopsy sites. These checks will be performed by Dr. Miller and/or trained members of his laboratory. At this time, you will also become familiar with the dynamometer that will be used during Visits 4 and 5 to measure your leg muscle strength and power. This will involve extending and flexing your legs at different speeds while in a seated position until you are comfortable performing this task.

Visit 4 (1.5-2 hours): Leg Strength, Physical Function and Start of Exercise Training Program

During your fourth visit, we will measure your leg muscle strength and power using a dynamometer. We will test the strength of your right and your left legs. For these tests, you will be asked to extend and flex your leg several times while in a seated position. For each leg, you will be asked to perform this movement at 7 different testing speeds, and each speed will require 3 repetitions (7 speeds x 3 repetitions = 21 repetitions). In addition to the voluntary contractions, electrical stimulation will be used to examine muscle activation. For this test, two self-adhesive electrode pads will be attached to your thigh, one near your knee and one at the top of your thigh. These pads will briefly (0.5 s) stimulate your thigh muscle and make it contract. This procedure will be performed several times until the current produces a muscle contraction that is about half the strength of your maximal voluntary contractions. Collectively, the leg muscle strength tests take approximately 30 minutes to complete. You will also be asked to complete the Advanced Short Performance Physical Battery (SPPB-A) to assess mobility function. The SPPB-A includes a short walk, static and dynamic balance assessments, and repeated chair stands. You will also be asked to complete the single-step test (SST) to measure limb performance unilaterally. To perform the SST, you will be asked to stand on one leg (test leg) on a 15 cm high, single step and must touch the ground with your other leg by performing a squat with the test leg and then return to the standing position. During this visit, we will also familiarize you with the muscle strength testing procedures on the dynamometer. Following the completion of the physical function tests, you will begin the exercise training program.

Visit 5 (1.5-2 hours): Physical Function and Leg Strength Tests

Approximately one-week before completing the 16-week exercise training program, you will be asked to complete the same tests that you did during Visit 4.

Visit 6 (3-4 hours): Body Composition, Blood Draw and Muscle Biopsy

After completing the 16-week exercise training program, you will be asked to undergo body composition tests (MRI and DEXA), a blood draw, and biopsies of the thigh muscle from your left and right legs, similar to Visit 2.

Visit 7 (5 minutes): Biopsy Site Check

Two to four days after your biopsies, you will stop by the Human Testing Center so we can check your biopsy sites. These checks will be performed by Dr. Miller and/or trained members of his laboratory.