The Role of Muscle Protein Breakdown in the Regulation of Muscle Quality in Frail Elderly Individuals

NCT ID: NCT03326648

Last Updated: 2018-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-01
• Study Completion Date: 2018-03-01

Brief Summary

The purpose of this study is to investigate mechanisms underlying the reduction in muscle quality (the ratio between muscle strength and muscle size) with aging, and to investigate how these factors are affected by strength training and protein supplementation. It is already established that muscle quality defined as the ratio between the strength and the size of a muscle is improved with strength training, even in frail elderly individuals. However, the relative contribution of factors such as activation level, fat infiltration, muscle architecture and single fiber function is unknown. The main focus of this study is to investigate the relationship between muscle quality and muscle protein breakdown, as insufficient degradation of proteins is hypothesized to negatively affect muscle quality.

Detailed Description

Aging is associated with impaired skeletal muscle function. This is evident not only by a reduced capacity to generate force and power at the whole muscle level, but also by a decline in individual muscle fiber contraction velocity and force generation. Combined with muscle atrophy, these changes lead to reduced muscle strength and quality and loss off physical function with age. Clinically, muscle quality may be a better indicator of overall functional capacity than absolute muscle strength. Thus, identifying the mechanisms underlying the age-related loss of muscle quality is of high relevance for the prevention of functional impairment with aging. The explanation for the loss of muscle quality with aging seems to be multifactorial, with alterations in voluntary muscle activation, muscle architecture, fat infiltration and impaired contractile properties of single muscle fibers being likely contributors. Single fiber specific force seems to be related to myosin heavy chain (MHC) content, which is thought to reflect the number of available cross-bridges. The reduction of single fiber specific force with aging may thus be a consequence of reduced synthesis of MHC and/or increased concentration of non-contractile tissue (e.g. intramyocellular lipids).

Some studies in mice also indicate attenuated activity in some of the pathways responsible for degradation of muscle proteins with aging (especially autophagy). As a result, damaged proteins and organelles are not removed as effectively as they should, which could ultimately compromise the muscle's ability to produce force. In addition, reduced efficiency of mitophagy and lipophagy (two specific forms of autophagy), may indirectly affect single fiber specific force, through oxidative damage by reactive oxygen species (ROS) and increased levels of intramyocellular lipids, respectively. Although animal studies indicate attenuated autophagic function, exercise seems to restore the activity in this pathway. Whether this also is the case in humans is unknown. Thus, the purpose of this study is to investigate how the different factors contributing to reduced muscle quality in frail elderly individuals, with emphasis on the relationship between muscle quality and autophagy, may be counteracted by a specific strength training program targeting muscle quality and muscle mass.

In this randomized controlled trial the investigators will aim to recruit frail elderly individuals, as muscle quality is shown to be low in this population. As a consequence, the potential for improved muscle quality is expected to be large. Subjects will be randomized to two groups; one group performing strength training twice a week for 10 weeks in addition to receiving daily protein supplementation. The other group will only receive the protein supplement. Several tests will be performed before and after the intervention period, including a test day where a biopsy is obtained both at rest, and 2.5 hours following strength training + protein supplementation or protein supplementation only. This will provide information about the regulation of muscle protein breakdown in a resting state, following protein intake and following strength training in combination with protein intake. As this will be done both before and after the training period, it will also provide information on how long-term strength training affects the activity in these systems.

Conditions

Sarcopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Strength training + protein supplement

Two sessions of strength training each week in addition to daily protein supplementation for 10 weeks.

Group Type: EXPERIMENTAL

Strength training

Intervention Type: OTHER

Heavy load strength training performed twice a week for 10 weeks.

Protein supplementation

Intervention Type: DIETARY_SUPPLEMENT

Dietary protein supplement (protein-enriched milk with 0,2 % fat). 0,33 l each day for 10 weeks.

Protein supplement

Daily protein supplementation for 10 weeks.

Group Type: EXPERIMENTAL

Protein supplementation

Intervention Type: DIETARY_SUPPLEMENT

Dietary protein supplement (protein-enriched milk with 0,2 % fat). 0,33 l each day for 10 weeks.

Interventions

Strength training

Heavy load strength training performed twice a week for 10 weeks.

Intervention Type: OTHER

Protein supplementation

Dietary protein supplement (protein-enriched milk with 0,2 % fat). 0,33 l each day for 10 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Resistance training

Eligibility Criteria

Inclusion Criteria

• Age > 65
• Frail or pre-frail according to the Fried Frailty Criteria or Short Physical Performance Battery (SPPB) score <6.
• Mini Mental State Examination score > 18

Exclusion Criteria

• Diseases or injuries contraindicating participation
• Lactose intolerance
• Allergy to milk
• Allergy towards local anesthetics (xylocain)
• Use of anticoagulants that cannot be discontinued prior to the muscle biopsy

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Padova

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Tine

INDUSTRY

Sponsor Role: collaborator

Truls Raastad

OTHER

Sponsor Role: lead

Responsible Party

Truls Raastad

Prof.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Truls Raastad, Prof.

Role: PRINCIPAL_INVESTIGATOR

Norwegian School of Sport Sciences

Locations

Norwegian School of Sport Sciences

Oslo, , Norway

Countries

Norway

Other Identifiers

STAS

Identifier Type: -

Identifier Source: org_study_id