Lysosomal Movement and Anabolic Resistance

NCT03032757 | Unknown

• 1 other identifier: RG_16-200
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional impairment and physical disability in the elderly. Maintenance or growth of muscle mass is mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle protein) in response to exercise and feeding. However, several investigations have shown that elderly individuals have a blunted protein synthetic response following protein intake. This inability of the elderly to properly respond to growth stimuli has been termed anabolic resistance and plays a significant role in the development of sarcopenia. However, the precise mechanisms underpinning anabolic resistance are unknown. It is well established that muscle protein synthesis at the molecular level is regulated by a cellular protein complex called mTORC1. When exposed to a growth stimulus, mTORC1 has been shown to associate with lysosomes, i.e. the intracellular organelles responsible for the breakdown of cellular proteins, and subsequently moving towards the cell periphery. This movement of lysosome-associated mTORC1 within the cell is believed to be vital for the activation of protein synthesis, as inhibition of lysosomal movement blunts mTORC1 activation in response to amino acids. Thus, dysregulation of lysosomal movement in ageing muscle may represent an underlying mechanism in the development of anabolic resistance. However, this area of research is unexplored in the context of human skeletal muscle. The investigators hypothesize that dysregulation of lysosomal movement plays a central role in the development of age-associated skeletal muscle anabolic resistance.

Conditions

Sarcopenia

Outcome Measures

Primary Outcomes (1)

• Lysosomal movement

  Changes in intracellular localization of lysosomes will be measured via immunofluorescence

  ~360 minutes

Secondary Outcomes (1)

• Lysosomal movement in isolated muscle cells

  ~30 minutes

Study Arms (4)

Resting leg of young males

EXPERIMENTAL

Dietary Supplement: Essential amino acids

Exercising leg of young males

EXPERIMENTAL

Dietary Supplement: Essential amino acids

Resting leg of elderly males

EXPERIMENTAL

Dietary Supplement: Essential amino acids

Exercising leg of elderly males

EXPERIMENTAL

Dietary Supplement: Essential amino acids

Interventions

Essential amino acids DIETARY_SUPPLEMENT

240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.

Exercising leg of elderly males; Exercising leg of young males; Resting leg of elderly males; Resting leg of young males

Eligibility Criteria

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

You may qualify if:

• Be a non-smoking male within the specified age range for each group (young; 18-35 yrs, old; 65-75 yrs)
• Have a BMI (body mass index, body weight/height in m2) between 18 and 25 kg/m2, which is considered a normal body mass index.
• Be in good general health: no cardiovascular diseases or metabolic diseases.

You may not qualify if:

• Health problems such as: heart disease , metabolic disease such as phenylketonuria, rheumatoid arthritis, uncontrolled hypertension, poor lung function, or any health condition that might put the participant at risk when participating in this study.
• Generalized neuromuscular disease (such as Parkinson's disease or motorneuron disease).
• Involvement in regular structured resistance exercise training at the time of the study.
• Consumption of any analgesic drugs, anti-inflammatory drugs, or medication that is known to affect protein metabolism (beta-blockers, corticosteroids, NSAIDs).
• Participants who have undergone muscle biopsy testing or isotope infusion procedures within the last 5 years.
• Allergic to lidocaine

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (1)

School of Sport, Exercise and Rehabilitation Sciences at University of Birmingham

Birmingham, West Midlands, B152TT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Sarcopenia

Interventions

Amino Acids, Essential

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

William Apro, Ph.D.

CONTACT

01214142875; w.apro@bham.ac.uk

Andrew Philp, Ph.D.

CONTACT

0121414 8872; a.philp@bham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D.

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 26, 2017
• Study Start: May 12, 2017
• Primary Completion: August 30, 2018
• Study Completion: August 30, 2018
• Last Updated: October 25, 2017

Record last verified: 2017-10

Locations

GB (1)