Aging
Conditions
Keywords
metabolism, exercise, sodium nitroprusside
Brief summary
The purpose of this study was to examine the role skeletal muscle perfusion plays in mediating muscle protein synthesis in healthy older and younger individuals. The investigators hypothesized that normalization of muscle perfusion in older men and women via exercise or infusion of a vasodilator would enhance nutritive flow and skeletal muscle protein synthesis in the elderly similar to that of their younger counterparts.
Detailed description
The purpose of this study was to examine muscle protein metabolism in healthy young and elderly subjects during pharmacologic vasodilation of the lower limb vasculature in combination with increased amino acids delivery. We obtained femoral arteriovenous blood samples and v. lateralis muscle biopsies during a primed continuous infusion of L-\[ring-13C6\] Phenylalanine. Muscle protein kinetics were measured in the basal state and during a 180 min infusion of sodium nitroprusside (SNP) and amino acids (Premsol 10%) (SNP+AA). Skeletal muscle microvascular recruitment and flow were measured during the basal state and SNP+AA using contrast-enhanced ultrasound (CEU).
Interventions
OTHERAerobic Exercise
45 minuties of treadmill walking was completed at 40% VO2 peak
DRUGSodium Nitroprusside
Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min
DIETARY_SUPPLEMENTAmino Acid Drink
7.5 gram Amino Acid drink
Sponsors
National Institute on Aging (NIA)
The University of Texas Medical Branch, Galveston
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
All inclusion criteria must be fulfilled throughout the study. At enrollment, subjects must fit the following criteria: 1. Age: young 18-40 yrs; elderly 60-85 yrs. 2. Availability of transportation (i.e., subjects must be able to provide their own transportation to UTMB). 3. Ability to sign informed consent (score \>24 on 30 item mini-mental status exam and no errors on assessment of judgment).
Exclusion criteria
None of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mixed Muscle Fractional Synthesis Rate (FSR) | Acute ( 8 hours) | The rate at which the body makes new muscle was assessed by determining the fractional synthesis rate (FSR). This technique determines how quickly new amino acids are used to make muscle. In this technique, a special (but natural and non-radioactive) version of an amino acid is infused into the blood. This special version of the amino acid is heavier than the most common version the same amino acid. This property allows it to be identified in a muscle sample. By determining how much of the special amino acid has accumulated over time in a muscle sample, the fractional synthesis rate can be determined. For example, if the rate were such that 1 of every 100 amino acids were of the special type after 1 day, the fractional synthesis rate would be 1% per day. In other words, 1/100 of the muscle would be newly made each day. |
Participant flow
Recruitment details
Young groups: Ages 18 - 40; Elderly groups: Ages 60 - 85
Participants by arm
| Arm | Count |
|---|---|
| Young Aerobic Exercise 45 minutes of treadmill walking completed at 40% VO2 peak. | 13 |
| Elderly Aerobic Exercise 45 minutes of treadmill walking completed at 40% VO2 peak. | 10 |
| Young Sodium Nitroprusside Sodium Nitroprusside (Nitropress) given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min. | 15 |
| Elderly Sodium Nitroprusside Sodium Nitroprusside (Nitropress) given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min. | 16 |
| Elderly Sodium Nitroprusside and Amino Acid Drink Sodium Nitroprusside (Nitropress) given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min and 7.5 gram amino acid drink taken orally. | 8 |
| Total | 62 |
Baseline characteristics
| Characteristic | Elderly Aerobic Exercise | Young Sodium Nitroprusside | Elderly Sodium Nitroprusside | Young Aerobic Exercise | Elderly Sodium Nitroprusside and Amino Acid Drink | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 0 Participants | 10 Participants | 0 Participants | 3 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 15 Participants | 6 Participants | 13 Participants | 5 Participants | 42 Participants |
| Age, Continuous | 67.4 years STANDARD_DEVIATION 5.1 | 26.4 years STANDARD_DEVIATION 5 | 68.1 years STANDARD_DEVIATION 5.9 | 27.2 years STANDARD_DEVIATION 5.9 | 67.1 years STANDARD_DEVIATION 4.4 | 49.2 years STANDARD_DEVIATION 21.2 |
| Region of Enrollment United States | 10 participants | 15 participants | 16 participants | 13 participants | 8 participants | 62 participants |
| Sex: Female, Male Female | 0 Participants | 10 Participants | 7 Participants | 0 Participants | 7 Participants | 24 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 9 Participants | 13 Participants | 1 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 10 | 2 / 15 | 2 / 16 | 0 / 8 |
| serious Total, serious adverse events | 0 / 13 | 0 / 10 | 0 / 15 | 1 / 16 | 0 / 8 |
Outcome results
Primary
Mixed Muscle Fractional Synthesis Rate (FSR)
The rate at which the body makes new muscle was assessed by determining the fractional synthesis rate (FSR). This technique determines how quickly new amino acids are used to make muscle. In this technique, a special (but natural and non-radioactive) version of an amino acid is infused into the blood. This special version of the amino acid is heavier than the most common version the same amino acid. This property allows it to be identified in a muscle sample. By determining how much of the special amino acid has accumulated over time in a muscle sample, the fractional synthesis rate can be determined. For example, if the rate were such that 1 of every 100 amino acids were of the special type after 1 day, the fractional synthesis rate would be 1% per day. In other words, 1/100 of the muscle would be newly made each day.
Time frame: Acute ( 8 hours)
Population: FSR was not calculated for the Elderly Sodium Nitroprusside with Amino Acid Drink arm of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Young Aerobic Exercise | Mixed Muscle Fractional Synthesis Rate (FSR) | Pre-intervention (either exercise or SNP) | 0.061 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.005 |
| Young Aerobic Exercise | Mixed Muscle Fractional Synthesis Rate (FSR) | Post -intervention (either exercise or SNP) | 0.098 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.009 |
| Elderly Aerobic Exercise | Mixed Muscle Fractional Synthesis Rate (FSR) | Pre-intervention (either exercise or SNP) | 0.070 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.006 |
| Elderly Aerobic Exercise | Mixed Muscle Fractional Synthesis Rate (FSR) | Post -intervention (either exercise or SNP) | 0.111 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.011 |
| Young Sodium Nitroprusside | Mixed Muscle Fractional Synthesis Rate (FSR) | Pre-intervention (either exercise or SNP) | 0.066 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.01 |
| Young Sodium Nitroprusside | Mixed Muscle Fractional Synthesis Rate (FSR) | Post -intervention (either exercise or SNP) | 0.090 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.008 |
| Elderly Sodium Nitroprusside (SNP) | Mixed Muscle Fractional Synthesis Rate (FSR) | Post -intervention (either exercise or SNP) | 0.095 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.009 |
| Elderly Sodium Nitroprusside (SNP) | Mixed Muscle Fractional Synthesis Rate (FSR) | Pre-intervention (either exercise or SNP) | 0.070 Fractional Synthesis Rate (pecent/hour) | Standard Error 0.004 |
| Elderly Sodium Nitroprusside and Amino Acid Drink | Mixed Muscle Fractional Synthesis Rate (FSR) | Pre-intervention (either exercise or SNP) | NA Fractional Synthesis Rate (pecent/hour) | — |
| Elderly Sodium Nitroprusside and Amino Acid Drink | Mixed Muscle Fractional Synthesis Rate (FSR) | Post -intervention (either exercise or SNP) | NA Fractional Synthesis Rate (pecent/hour) | — |