Inflammaging and Muscle Protein Metabolism

NCT03308747 | Completed

• 1 other identifier: INFLAMMAGING-UTH
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammaging; Sarcopenia

Keywords

Low-grade systemic inflammation; Muscle protein synthesis; Proteasome activation; Anabolic signaling; Aging; Sarcopenia

Outcome Measures

Primary Outcomes (5)

• Systemic inflammation

  Levels of systemic inflammation will be assessed by measuring serum levels of hs-CRP, IL-6 and TNF-α.

  At baseline.

• Change in muscle protein synthesis (MPS)

  Using deuterium oxide (D2O) 70% atom administration. Individuals will consume a single bolus of 150ml D20 the day before the clinical trial and muscle biopsy samples, collected before and after the exercise bout and protein ingestion, will be analyzed for isotopic measurement using GC-P-IRMS.

  At baseline and 180 min following protein ingestion.

• Change in intracellular signaling proteins in muscle

  Phosphorylation levels of Akt, mammalian target of rapamycin (mTOR), p70S6K and ribosomal protein S6 (rpS6) will be measure using western blotting.

  At baseline and 180 min following protein ingestion.

• Change in proteasome activities in muscle

  Chymotrypsin-like (CT-L), caspase-like (C-L) and trypsin-like (T-L) proteasome activities will be assayed with hydrolysis of the fluorogenic peptide LLVY-AMC, LLE-AMC and LSTR-AMC, respectively.

  At baseline and 180 min following protein ingestion.

• Change in protein expression level of proteasome subunits

  Immunoblot analysis will be used to detect protein expression levels of proteasome (β5, β2 and β1) and immunoproteasome (β5i, β2i and β1i) subunits.

  At baseline and 180 min following protein ingestion.

Secondary Outcomes (18)

• Resting metabolic rate (RMR)

  At baseline.

• Physical activity

  Over a 7-day period at baseline.

• Dietary intake

  Over a 7-day period at baseline.

• Reduced glutathione in blood

  At baseline.

• Oxidized glutathione in blood

  At baseline.

Study Arms (2)

High systemic inflammation

EXPERIMENTAL

Individuals assigned in the high systemic inflammation group will be characterized by IL6: ≥ 1.7 pg/ml and hs-CRP: \> 2.0 mg/L.

Dietary Supplement: Instantized Whey Protein Isolate

Low systemic inflammation

ACTIVE COMPARATOR

Individuals assigned in the high systemic inflammation group will be characterized by IL6: \< 1.7 pg/ml and hs-CRP: \< 1.0 mg/L.

Dietary Supplement: Instantized Whey Protein Isolate

Interventions

Instantized Whey Protein Isolate DIETARY_SUPPLEMENT

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.

High systemic inflammation; Low systemic inflammation

Eligibility Criteria

• Age: 63 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Thessaly: lead

Study Sites (1)

Exercise Biochemistry Laboratory, School of Physical Education & Sports Sciences, University of Thessaly

Trikala, 42100, Greece

Location

MeSH Terms

Conditions

Sarcopenia

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• DIMITRIOS DRAGANIDIS, PhDc

  UNIVERSITY OF THESSALY, SCHOOL OF PHYSICAL EDUCATION & SPORTS SCIENCES

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 13, 2017
• Study Start: September 1, 2017
• Primary Completion: February 15, 2018
• Study Completion: May 30, 2018
• Last Updated: July 19, 2018

Record last verified: 2017-10

Locations

GR (1)