CLINICAL TRIAL: INSULIN AND SARCOPENIA IN THE ELDERLY (CYCLE NO, 2)
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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Aging is associated with specific skin changes that increase the risk of injury, such as pressure ulcers, and delay wound healing, thus complicating the course of other illnesses in seniors. Skin aging is due to both age and prolonged exposure to sunlight. We will focus on the skin changes that are not due to sunlight exposure. Specific Aims and Procedures (summary): 1) To determine if mixed skin protein turnover (synthesis and breakdown) can be used as alternative measures of dermal collagen protein turnover (synthesis and breakdown) in human subjects. 2) To determine if skin protein synthesis is lower and/or breakdown is faster in older individuals as compared to younger controls. Experimental Design (summary): Volunteers will be recruited by an institutional review board-approved advertisement that will be posted at the University of Texas Medical Branch, local newspapers, and social centers, and by word of mouth. We will study 8 younger (18 - 35 years) and 8 older (>70 years) men. Significance (summary): We hope to learn what the normal skin turnover is in healthy younger people, and we also hope to learn if the skin turnover changes with age. We will measure short-term skin growth and breakdown in younger and older people.
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The focus of this project is to explore how muscles grow. Muscle wasting is a common phenomenon in many conditions, such as cancer, AIDS, trauma, sepsis, kidney failure, and is also particularly prevalent in the elderly.
Specific Aims and Procedures (summary): (1) To determine the magnitude of the short-term response of muscle growth to feeding when the food is given before or after a bout of resistance exercise. (2) To determine the magnitude of the short-term response of muscle growth to food that provides an amount of energy that either matches or exceeds the amount of energy used during the exercise. (3) To determine the differences between women and men in the short-term response of muscle growth to weight lifting alone and in combination with feeding when ingested before or after a bout of weight lifting exercise. The procedures we will use in order to address these specific aims include the use of femoral catheters, weight lifting exercise, blood and breath collection and taking muscle biopsies. During each experiment we will be continuously infusing stable isotopes. Stable isotopes are not radioactive and can be given safely to humans. These stable isotopes allow us to be able to measure short-term muscle growth in humans.
Significance (summary): These studies will provide insight into the mechanisms that regulate human muscle growth, and will be utilized as a basis from which to develop interventions for improving muscle growth in conditions such as aging, trauma, cancer, and AIDS.
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Muscle mass and function progressively decline with aging. This process has been termed sarcopenia, and is associated with increased risk of falls and vulnerability to injury, especially bone fracture, which increase the risk of functional dependence.
Our preliminary results suggest that there is a change in the response of muscle protein synthesis to insulin in the elderly, which can compromise the positive effect of amino acids on muscle protein gain. Our goal is to determine the mechanisms underlying the age-related insulin resistance of muscle proteins, which will allow us to define specific interventions to target this defect and provide the scientific basis for the prevention and treatment of sarcopenia.
Subjects will be assigned randomly to any of the following groups: for 18-35 years old the possible groups are the following: insulin alone, insulin with L-NMMA, L-NMMA alone; meal ; for 65 or older the possible groups will be the following: insulin alone, insulin with sodium nitroprusside; insulin with exercise; meal alone; meal with sodium nitroprusside; meal with exercise. We will measure the rate of metabolism, exchange, or turnover of amino acids in the body.
Overall, we believe that this proposal will allow us to better delineate the changes in muscle metabolism with aging, thus providing a solid scientific basis for future intervention to prevent and treat muscle loss with aging (sarcopenia).
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our studies in the past have focused on the short term effects of exercise and amino acids in sedentary subjects. We would like to expand our research to include recreationally active middle aged people looking at the effect of essential amino acid on muscle growth.
We hypothesize that long-term nutritional supplementation with essential amino acids will grow muscle and increase strength in healthy, trained middle-aged people.
We will determine if long-term nutritional supplementation with essential amino acids can grow muscle and increase strength in healthy, trained middle aged people.
Enrolled subjects will be randomized to receive supplement or a placebo (i.e. like a sugar pill ) every day for one year. They will be tested every four months to check for muscle growth, strength testing, and safety of the supplements. At the end of the year all tests will be performed again to get the final results.
This pilot study will serve to determine feasibility and safety of a nutritional intervention for muscle growth in trained middle-aged persons, and will allow us to collect preliminary data for a larger clinical trial to determine the optimal dose and composition of nutritional supplements for the prevention of muscle weakness and loss with aging.
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rapamycin (mTOR) signaling pathway plays a significant role in stimulating translation initiation and muscle protein synthesis. Though both muscular contraction and hypoxia have been demonstrated to acutely up regulate AMPK activity, effect of hypoxia per se on muscle protein turnover is unknown. Additionally, recent studies have shown that hypoxia can up-regulate the mTOR signaling pathway through a transcription factor called hypoxia-inducible factor-1 (HIF1). Hypoxia induced angiogenesis and cardiac cell growths have been linked to HIF1; therefore, resistance exercise combined with restricted venous blood flow may further stimulate mTOR signaling pathway through HIF1. The specific aims are to: 1) to determine which component(s) of the mTOR signaling pathway are modified with muscular contraction combined with local hypoxia in older men. 2) To determine whether blood flow restriction during low-intensity exercise produces a larger increase in muscle protein synthesis than regular resistance exercise alone in older men. We will study groups of 24 older (60 yrs and above yrs) men after an overnight fast. The protocol is designed to study the modulations in mixed muscle protein fractional synthetic rate (FSR) and total protein content and phosphorylation status of components of the mTOR signaling pathway involved in translation initiation (mTOR, p70S6K, eIF2B, HIFs and AMPK) at rest and after low intensity resistance exercise with or without vascular occlusion. These studies will provide insight into the cellular mechanisms responsible for the enhanced hypertrophic effect of resistance exercise combined with reduced muscular blood flow.
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The loss of muscle mass leads to overall weakness, immobility and physical dependence, and can be responsible for an impaired response to stress, which is associated with higher mortality rates during infection, surgery, and trauma.
Amino acids and weight lifting can both increase muscle size. It has been shown that muscle growth post-exercise is less in the elderly as compared to young volunteers. However, there have been no studies that have examined the combined effect of amino acids and resistance exercise.
We hypothesize that amino acid ingestion following a bout of weight lifting exercise will improve short-term muscle growth in older men.
The specific aims are to determine if 20 grams of essential amino acids ingested one hour following a bout of weight lifting exercise will stimulate short-term muscle growth in older men to the same extent as seen in the young.
Six healthy young and older male volunteers will be enrolled. One hour following the exercise session each subject will receive 20 grams of essential amino acids. We will then assess changes in blood amino acid content, hormone changes such as insulin and testosterone from the blood samples. Each muscle sample will be used to measure muscle protein synthesis and to assess changes in cell signaling pathways the control protein synthesis.
These studies will provide insight into why muscle loss is occurring with age and will then help us to develop scientifically-based interventions for improving muscle size.
