Inflammaging and Muscle Protein Metabolism
Condition: Inflammaging; Sarcopenia
MeSH terms: Sarcopenia
Study type: Interventional

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.
    

Intervention name(s): Instantized Whey Protein Isolate
Intervention type(s): Dietary Supplement
Intervention description(s): 0,4 g of whey protein isolate/kg body weight will be ingested as a bolus of 250 ml immediately after the resistance exercise bout.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Low-grade systemic inflammation; Muscle protein synthesis; Proteasome activation; Anabolic signaling; Aging; Sarcopenia