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Mechanisms of Age-Related Muscle Loss

2017年4月12日 更新者:University of Birmingham

Influence of Increasing Physical Activity on Body Composition, Metabolic Health and Muscle Anabolism in Old Obese Adults

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.

調査の概要

詳細な説明

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.

研究の種類

観察的

入学 (実際)

38

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

65年~85年 (高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

サンプリング方法

非確率サンプル

調査対象母集団

  • Young lean healthy inidivduals aged 18-35.
  • Lean healthy older individuals aged 65-85.
  • Obese inactive older individuals aged 65-85.

説明

Inclusion Criteria:

  1. Age: 65-85 years old for older individuals and 18-35 years for younger individuals
  2. Sex: Men and women
  3. BMI: 18-25 kg/m2 for healthy non-obese young and elderly control group and >30 kg/m2 for obese older participants.
  4. Diagnosis / General Health: For healthy elderly, good general health (no known cardiovascular or metabolic disease), nonsmokers, accustomed to normal levels of activity as assessed by pedometer and accelerometer devices during baseline testing (>5000 steps per day). For obese elderly, general good health (no known cardiovascular or metabolic disease), nonsmokers, with low levels of physical activity as assessed by pedometer and accelerometer devices during baseline testing (<4000 steps per day). Fasting blood glucose must be <5.6 mmol/mL for healthy older adults and between 5.6 and 6.9 mmol/mL for obese older adults. Fasting concentrations of A1C should be <5.7% for healthy and between 5.7 and 6.4% for prediabetic older adults. These values are in line with the type 2 diabetes classification listed by The American Diabetes Association (DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010).
  5. Compliance: understands and is willing, able and likely to comply with all study procedures and restrictions.
  6. Consent: demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent.

Exclusion Criteria:

  1. Health problems such as: heart disease, rheumatoid arthritis, diabetes, poor lung function, uncontrolled hypertension, or any health conditions that might put the participant at risk for this study.
  2. Recent failure to obtain clearance for exercise participation from family physician/medical doctor.
  3. Regular consumption of any analgesic or anti-inflammatory drug(s), prescription or nonprescription.
  4. Taking any medications known to affect protein metabolism (i.e. b-blockers, corticosteroids, nonsteroidal anti-inflammatories, or prescription strength acne medications). Medications will be deemed inappropriate based on the Chief Investigators discretion
  5. Individuals who complete fewer than 1000 steps per day (as assessed by pedometer prior to the study) or those who participate in regular structured exercise (running or strength training) more than 2 times per week.
  6. Participants will be excluded if they fail to comply with the physical activity demands of the study. Exclusion will occur if the following are not met. Failure to meet the expected daily step count target on more than one occasion per week during the 21 day intervention will be deemed as failure to comply.
  7. Participants who have previously (within 5 years of the present study) undergone infusion of an amino acid tracer and/or had 4 or more muscle biopsies obtained from the quadriceps region will be excluded.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 観測モデル:コホート
  • 時間の展望:断面図

コホートと介入

グループ/コホート
Obese older individuals
Lean older individuals
Young lean individuals

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Myofibrillar protein synthesis rates via mass spectrometry
時間枠:2 years
Postabsorptive and postprandial myofibrillar protein synthesis rates between groups and following the activity intervention
2 years

二次結果の測定

結果測定
メジャーの説明
時間枠
Muscle fibre properties via immunohistochemical staining
時間枠:2 years
muscle fibre type (i.e. I and II) and cross sectional area
2 years
Muscle fibre lipid content immunofluorescent staining
時間枠:2 years
Intramyocellular lipid content in Type I and II fibres
2 years
Physical activity levels via accelerometry
時間枠:2 years
Daily average time spent in sedentary, light, moderate or vigorous intensity activity
2 years
Inflammation via plasma/insulin assays
時間枠:2 years
Blood markers of inflammation, interleukin 6 and c-reactive protein
2 years
Insulin sensitivity via plasma assays
時間枠:2 years
Blood samples will be analyzed for insulin, glucose and hbA1C for indication of whole-body insulin sensitivity
2 years
Body composition via dual x-ray absorptiometry
時間枠:2 years
DXA-derived fat and fat free mass will be measured
2 years
Intramuscular signaling via western blot
時間枠:2 years
Western blots for phosphorylation of key anabolic signaling proteins
2 years
Dietary intake via dietary logs
時間枠:2 years
Diet logs will be assessed for total energy and macronutrient intake
2 years
Daily step count by pedometer
時間枠:2 years
Average daily step count assessed via waist worn pedometer
2 years

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出版物と役立つリンク

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研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2014年8月1日

一次修了 (実際)

2016年3月1日

研究の完了 (実際)

2016年8月1日

試験登録日

最初に提出

2017年3月28日

QC基準を満たした最初の提出物

2017年4月12日

最初の投稿 (実際)

2017年4月13日

学習記録の更新

投稿された最後の更新 (実際)

2017年4月13日

QC基準を満たした最後の更新が送信されました

2017年4月12日

最終確認日

2017年4月1日

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