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Skeletal Muscle Inflammation, Oxidative Stress and DNA Repair in Age-Related Sarcopenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Florida
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT02116166
First received: April 14, 2014
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

The purpose of this research study is to investigate how and why the loss of muscle mass occurs with aging. Tissue collected from young subjects will be compared to previously collected tissue from elderly subjects, as well as previously collected data on muscle function/mass to further investigate cellular and molecular pathways that have recently been shown to be important for the aging process in muscle. The Principal Investigator (PI) and the study team will look for specific proteins (called biomarkers) that can be present in the muscle tissue in various amounts in different individuals. This study will increase the investigators understanding of the processes of muscle atrophy (loss of mass) and functional loss at older age and will help to find new treatments and interventions aimed at improving the quality of life and independence of America's rapidly expanding elderly population.


Condition
Sarcopenia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Claude D. Pepper Older Americans Independence Center (OAIC); Skeletal Muscle Inflammation, Oxidative Stress and DNA Repair in Age-Related Sarcopenia

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Tumor Necrosis Factor alpha (TNF-alpha) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • tumor-necrosis factor receptor-1 (TNFR1) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • Phospho-Inhibitory Subunit Of NF-KBα (pIkBα) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • Chemokine (C-C motif) ligand 2 (CCL2) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • zinc transporter (ZIP) 14 [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • Interleukin 6 (IL-6) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • Interleukin (IL) 11β [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • Interleukin 8 (IL-8) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • C-C chemokine receptor type 2 (CCR2) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • zinc transporter 14 (ZIP14) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Inflammation marker; measured in muscle biopsy specimens.

  • copper [ Time Frame: baseline ] [ Designated as safety issue: No ]
    metals; measured in muscle biopsy specimens.

  • zinc [ Time Frame: baseline ] [ Designated as safety issue: No ]
    metals; measured in muscle biopsy specimens.

  • iron [ Time Frame: baseline ] [ Designated as safety issue: No ]
    metals; measured in muscle biopsy specimens.

  • ribosome profiling [ Time Frame: baseline ] [ Designated as safety issue: No ]
    DNA damage on pattern and dynamics of mRNA translation in human muscle tissue; measured in muscle biopsy specimens.


Biospecimen Retention:   Samples With DNA

Skeletal muscle biopsy


Estimated Enrollment: 10
Study Start Date: May 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Young
Young (20-35 years old)
Old
Older (70-99 years old)

Detailed Description:

For this project, we will continue to gain mechanistic insight into age-related muscle loss and to maximize the utility of the tissue we previously collected (Claude D. Pepper Older Americans Independence Center (OAIC); Skeletal muscle apoptosis and physical performance; Oxidative RNA/DNA damage and repair in aged human muscle (Developmental Study), IRB # 429-2005) and we will collect muscle tissue from additional young subjects. This project will specifically test whether inflammatory pathways and DNA repair mechanisms are altered and/or involved in the development of sarcopenia and the related decline in physical function observed in the elderly.

Aim 1. We will further determine the association of skeletal muscle mass and function with intramuscular mediators of inflammation. Focus will be on inflammatory proteins (e.g.,TNF, TNFR1, pIkBα, pIKKb, CCL2, ZIP14, ZnT2) and genes (e.g., IL-6, TNFa, IL11β, IL-8, CCL2, CCR2, NFkB p50, NFkB p65, ZIP14) and metals (e.g., copper, zinc, and iron). We hypothesize that the majority of these markers will be upregulated in muscle from older individuals when compared to young.

Aim 2. For the first time, we will determine the age related effect of DNA damage on pattern and dynamics of mRNA translation in human muscle tissue by genome wide analysis using "ribosome profiling." The recently developed deep-sequencing techniques of RNA-seq and "ribosome profiling" will be implemented on human muscle. This will allow us to explore on a genomic scale and at single-nucleotide resolution, the effect of age-related DNA damage on transcriptional fidelity and translational kinetics. Importantly, for the first time, these phenotype changes will be compared with genome mapping of DNA damage, a major factor driving mammalian aging. We hypothesize that older muscle has greater modification of translational patterns compared to young muscle.

Muscle tissue samples remaining following the completion of this research will be stored and used in the future to explore new avenues of research related to aging.

  Eligibility

Ages Eligible for Study:   20 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Young (age 20-35 years; N =10)

Criteria

Inclusion Criteria:

  • males and females aged 20-35.
  • willing and able to give informed consent.

Exclusion Criteria:

  • High physical activity level (i.e., the subject has spent greater than 300 minutes per week in the past 2 month performing structured physical activity, such as exercising at a gym and/or weight training)
  • Active treatment for cancer or history of cancer in the past 3 years
  • Congestive heart failure NYHA Class III or IV
  • Previous stroke with upper and/or lower extremities involvement within the last 6 months
  • Peripheral vascular disease Fontaine Class III/IV
  • History of life-threatening cardiac arrhythmias, stroke, severe Parkinson's disease or severe neurological disorders likely to interfere with physical function
  • Renal disease requiring dialysis
  • Lung disease requiring steroids
  • Lower extremity amputation
  • Complicated diabetes
  • Life-threatening illnesses with an estimated life expectancy less than 1 year
  • Anticoagulant therapy (aspirin use is allowed, but participants will be asked to stop taking it 48 hours prior to muscle biopsy)
  • Involved in active weight loss > 5 kg in prior 3 months
  • Pregnancy (determined by a pregnancy test)
  • Lidocaine allergy

Temporary exclusion criteria:

  • Recent bacterial infection (< 2 weeks)
  • Acute febrile illness in previous 2 months
  • High blood pressure (i.e., BP ≥ 160/90 mm Hg) at the visit (subject will be referred to his/her physician and reevaluated after appropriated therapy being instituted)
  • Taking aspirin within 48 hours preceding biopsy
  • Performing exercise 48 hours prior to the biopsy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02116166

Contacts
Contact: Michael Marsiske, PhD marsiske@PHHP.UFL.EDU

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32611
Contact: Michael Marsiske, PhD       marsiske@PHHP.UFL.EDU   
Sub-Investigator: Thomas Buford, PhD         
Sub-Investigator: Anna-Maria Joseph, PhD         
Sub-Investigator: Marco Pahor, MD         
Sub-Investigator: Bhanu Sandesara, MD         
Sub-Investigator: Diana Barb, MD         
Sub-Investigator: Todd Manini, PhD         
Sub-Investigator: Ronald Cohen, PhD         
Sub-Investigator: Stephen Anton, PhD         
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Christiaan Leeuwenburgh, PhD University of Florida
  More Information

Additional Information:
No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02116166     History of Changes
Other Study ID Numbers: 201300790, 2P30AG028740
Study First Received: April 14, 2014
Last Updated: July 31, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of Florida:
aging
sarcopenia
mitochondria
skeletal muscle
inflammation

Additional relevant MeSH terms:
Myositis
Inflammation
Sarcopenia
Atrophy
Muscular Atrophy
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathologic Processes
Pathological Conditions, Anatomical
Signs and Symptoms

ClinicalTrials.gov processed this record on November 20, 2014