Mechanisms of Age-Related Muscle Loss
Condition: Sarcopenic Obesity; Muscle Weakness; Protein Metabolism Disorder; Physical Activity
MeSH terms: Muscle Weakness; Metabolic Diseases
Study type: Observational

Summary: 
      Two independent, but interrelated conditions that have a growing impact on healthy life
      expectancy and health care costs in developed nations are the age related loss of muscle mass
      (sarcopenia) and obesity. Sarcopenia affects approximately one third of adults over 60 years
      of age and more than 50% of those over 80 years, which is of concern when one considers that
      the most rapidly expanding population demographic in the UK is adults >80 years of age.

      Skeletal muscle is important in regulating blood glucose and insulin sensitivity. Thus,
      sarcopenia may play a role in exacerbating insulin resistance and progression toward Type II
      diabetes (T2D). Indeed, the highest incidence of T2D in the UK has been noted to occur in
      adults >65 years. Obesity is a major risk factor for chronic diseases including T2D and
      cardiovascular disease. Progression towards obesity is associated with a concomitant decrease
      in muscle mass, producing an unfavorable ratio of fat to muscle. Thus, obesity in old age may
      exacerbate the progression of sarcopenia.

      For the proposed study the investigators will conduct preliminary laboratory tests to
      characterize body composition, insulin sensitivity, systemic inflammation, aerobic capacity
      and muscle protein metabolism (in the fasted and fed state) in healthy older and obese older
      adults for comparison against healthy young individuals.
    

Detailed description: 
      Twenty healthy young (aged 18-35), healthy old and obese older adults (aged ≥65) will be
      recruited. Old groups will be matched for age and sexual dimorphism. Obese participants will
      be classed as prediabetic based on a fasting A1C between 5.7 and 6.4% and impaired fasting
      glucose between 5.6 and 6.9 mmol/L. Obese participants will habitually take between 2000-5000
      steps per day, whilst healthy young and old participants will complete >5000 steps per day.

      VISIT 1 Preliminary assessments - Over a 3day period, participants will be instructed to wear
      a portable pedometer, to allow visual feedback on step count, and an armband accelerometer to
      determine habitual daily energy expenditure and the intensity of physical activity. In
      addition, participants will log their dietary intake.

      VISIT 2 Body composition and metabolic profiling After consuming a standardized meal the
      previous evening, participants will report to the Wellcome Trust Clinical Research Facility
      in a 10 hour fasted state at approximately 09.00. Participants will be weighed in light
      clothing and blood pressure will be measured. Thereafter, body composition will be determined
      using dual energy Xray absorptiometry (DXA) and resting metabolic rate (RMR) via ventilated
      hood and continuous gas collection. Following RMR, a catheter will be inserted into a forearm
      vein and a resting, fasted blood sample obtained to determine postprandial insulin
      sensitivity using the HOMA-IR index.

      VISIT 3 Muscle protein metabolism Participants will return to the lab in a 10 hour
      fasted-state at approximately 07.00 having refrained from strenuous exercise for 48 hours
      previously. Catheters will be inserted into the antecubital vein of both forearms. A primed,
      continuous infusion of isotopically labeled amino acid will be infused into one arm and the
      other will be used for frequent blood sampling. Muscle biopsies will be obtained 3 and 7
      hours into the infusion to determine postabsorptive and postprandial rates of muscle protein
      synthesis.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        -  Young lean healthy inidivduals aged 18-35.

          -  Lean healthy older individuals aged 65-85.

          -  Obese inactive older individuals aged 65-85.