Clinical trial NCT03308747: Inflammaging and Muscle Protein Metabolism
Official title: Effects of Low-grade Systemic Inflammation on Muscle Protein Synthesis and Breakdown in the Aged Skeletal Muscle.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Inflammaging
Sarcopenia
Keywords: Low-grade systemic inflammation
Muscle protein synthesis
Proteasome activation
Anabolic signaling
Aging
Sarcopenia
Lead sponsor: University of Thessaly
Sponsor class: OTHER
First posted: 2017-10-13
Enrollment: 44
Sex: MALE
Minimum age (years): 63
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The development of a low-grade, chronic, systemic inflammation observed in the elderly (inflammaing) has been associated with increased risk for skeletal muscle wasting, strength loss and functional impairments. According to studies performed in animals and cell cultures increased concentrations of pro-inflammatory cytokines such as IL-6 and TNF-α as well as increased levels of hs-CRP lead to elevated protein degradation through proteasome activation and reduced muscle protein synthesis (MPS) via downregulation of the Akt-mTOR signaling pathway. However, evidence regarding the effects of inflammaging on skeletal muscle mass in humans is lacking. Thus, the present study will compare proteasome activation and the protein synthetic response in the fasted and postprandial period between older adults with increased systemic inflammation and their healthy control counterparts.

Detailed description: A total number of \> 60 male, older adults aged 63-73 years will be initially screened for systemic levels of hs-CRP and IL-6. Of these, 24 individuals that will comply with the study criteria will be allocated to either a High (IL6: ≥ 1.7 pg/ml; hs-CRP: \> 1.0 mg/L) (n=12) or a Low (IL6: \< 1.7 pg/ml; hs-CRP: \< 1.0 mg/L) (n=12) systemic inflammation group. Approximately 2 weeks before the experimental trial, anthropometry, resting metabolic rate (RMR), body composition (with DXA), sarcopenia status, functional capacity and the knee-extension one repetition maximum (1RM) will be assessed in individuals from both groups. In addition, levels of habitual physical activity will be assessed using accelerometry (over a 7-day period) and daily dietary intake will be monitored through 7-day diet recalls in all participants. 1 week before the experimental day an oral glucose tolerance test (OGTT) will be also performed over a 2-hour period, with blood sampling every 15min during the first hour and every 30min during the second hour. The day before the experimental trial, participants will consume 150ml of D2O 70% atom as a bolus. In the experimental day, participants will arrive at the laboratory after an overnight fast and a baseline blood sample and a muscle biopsy from vastus lateralis muscle will be collected. Immediately after, participants will perform 8 sets with 10 repetitions at 80% of 1RM and 2 min rest between each set, on a knee-extension machine. After exercise, they will ingest 0.4 g whey protein isolate/kg body weight as single bolus and then they will remain in a sitting position over a 3-hour period. Blood samples will be collected every 30min during the 3-hour postprandial period while a second muscle biopsy will be obtained at 3h.

Eligibility criteria: Inclusion Criteria:

* Non-smokers.
* BMI ≥18.5 \& BMI ≤ 35 kg/m2.
* Moderately active but with no regular participation in heavy resistance exercise within the last 6 months.
* Absence of chronic disease (i.e. cancer, metabolic, cardiac, or neurological diseases).
* Free and independently living.

Exclusion Criteria:

* Organ failure (unstable, renal, respiratory, liver).
* Chronic use of corticosteroid medication.
* Recent use of antibiotics.
* Presence of frailty.
* Body weight variation over the past 6mo \> 10% or weight loss of more than 3kg in the last 3 months.
* Use of anti-inflammatory or lipid-lowering medication (i.e., statins).
* Use of medication interacting with muscle metabolism.

Primary outcomes:
measure: Systemic inflammation
timeFrame: At baseline.
measure: Change in muscle protein synthesis (MPS)
timeFrame: At baseline and 180 min following protein ingestion.
measure: Change in intracellular signaling proteins in muscle
timeFrame: At baseline and 180 min following protein ingestion.
measure: Change in proteasome activities in muscle
timeFrame: At baseline and 180 min following protein ingestion.
measure: Change in protein expression level of proteasome subunits
timeFrame: At baseline and 180 min following protein ingestion.
Secondary outcomes:
measure: Resting metabolic rate (RMR)
timeFrame: At baseline.
measure: Physical activity
timeFrame: Over a 7-day period at baseline.
measure: Dietary intake
timeFrame: Over a 7-day period at baseline.
measure: Reduced glutathione in blood
timeFrame: At baseline.
measure: Oxidized glutathione in blood
timeFrame: At baseline.
measure: Protein carbonyls in serum
timeFrame: At baseline.
measure: Total antioxidant capacity
timeFrame: At baseline.
measure: Malondialdehyde in serum
timeFrame: At baseline.
measure: White blood cell count in blood
timeFrame: At baseline.
measure: Insulin sensitivity
timeFrame: At baseline.
measure: Glucose concentration in blood
timeFrame: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
measure: Insulin concentration in blood
timeFrame: At baseline and at 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following protein ingestion.
measure: Body composition
timeFrame: At baseline
measure: Body Mass Index (BMI)
timeFrame: At baseline
measure: Skeletal muscle index
timeFrame: At baseline
measure: Grip strength
timeFrame: At baseline
measure: Functional performance
timeFrame: At baseline
measure: Lower limb muscle strength
timeFrame: At baseline
Other outcomes:
Locations:
city: Tríkala
country: Greece
facility: Exercise Biochemistry Laboratory, School of Physical Education & Sports Sciences, University of Thessaly
Study officials:
affiliation: UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES
name: DIMITRIOS DRAGANIDIS, PhDc
role: PRINCIPAL_INVESTIGATOR
References: