Skeletal Muscle Inflammation, Oxidative Stress and DNA Repair in Age-Related Sarcopenia
Condition: Sarcopenia
MeSH terms: Myositis; Sarcopenia; Inflammation
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Young (age 20-35 years; N =10)
      
Biospecimen description: 
      Skeletal muscle biopsy
    
Keywords: aging; sarcopenia; mitochondria; skeletal muscle; inflammation