Inflammaging and Muscle Protein Metabolism

Effects of Low-grade Systemic Inflammation on Muscle Protein Synthesis and Breakdown in the Aged Skeletal Muscle.

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.

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.

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.