Adipose tissue inflammation and muscle protein metabolism in older adults Nutritional, Metabolic, Endocrine
Conditions
Interventions
Sponsors
Eligibility
Inclusion criteria
Inclusion criteria: Older People 1. Age 65 to 75 years 2. Postmenopausal women must be > 1 year since last menses 3. Able to provide informed consent 4. Willing and able to comply with all study procedures, including maintenance of habitual dietary intake, exercise, and medication use during the study period. Younger People 1. Age 20-30 years 2. Able to provide informed consent 3. Willing and able to comply with all study procedures, including maintenance of habitual dietary intake, exercise, and medication use during the study period.
Exclusion criteria
Exclusion criteria: Older People 1. Living in a residential care home 2. Unstable or clinically active pulmonary, cardiac, hepatic, renal, endocrine, hematologic, immunologic, neurologic, psychiatric or biliary disorders. ‘Unstable’ refers to complications of a condition that are not controlled by medication or lifestyle and which require frequent monitoring and testing by a health professional. Stable chronic disease is not an exclusion criterion unless specified. 3. Diagnosed Type 1 or Type 2 Diabetes Mellitus or other metabolic disease(s) that would affect study outcomes 4. Diagnosed autoimmune condition 5. Diagnosed osteoarthritis affecting more than one joint 6. Past or current cancer diagnosis and treatment that required systemic treatment 7. Severe hypertension (systolic blood pressure >/= 180 mmHg and/or diastolic blood pressure >/= 120 mmHg), as defined by blood pressure measured at Visit 1 8. Current tobacco or recreational drug use 9. Reported changes to use of thyroid, antihypertensive, antidepressant or statin medications within 30 days of Visit 1 10. Taking medications that will interfere with the study outcomes 11. Regular participation in resistance training (at least once a week). 12. High levels of non-recreational exercise (> 6h per week of high-intensity exercise or sport) 13. Fat Mass Index (FMI) 12 kg/m2 (Men) and 16 kg/m2 (Women) 14. Known negative reaction to lidocaine anaesthetic and/or taking warfarin 15. Not weight stable in the prior 3 months (> 5% weight change) 16. Presence of injuries or conditions that would prevent completion of resistance exercise 17. Unable to converse in English Younger People 1. Unstable or clinically active pulmonary, cardiac, hepatic, renal, endocrine, hematologic, immunologic, neurologic, psychiatric or biliary disorders. ‘Unstable’ refers to complications of a condition that are not controlled by medication or lifestyle and which require frequent monitoring and testing by a health professional. Stable chronic disease is not an exclusion criterion unless specified. 2. Diagnosed Type 1 or Type 2 Diabetes Mellitus or other metabolic disease(s) that would affect study outcomes. 3. Diagnosed autoimmune condition. 4. Diagnosed osteoarthritis affecting more than one joint. 5. Past or current cancer diagnosis and treatment that required systemic treatment. 6. Severe hypertension (systolic blood pressure = 180 mmHg and/or diastolic blood pressure = 120 mmHg), as defined by blood pressure measured at Visit 1. 7. Current tobacco or recreational drug use. 8. Reported changes to use of thyroid, antihypertensive, antidepressant or statin medications within 30 days of Visit 1. 9. Taking medications that will interfere with the study outcomes. 10. Regular participation in resistance training (at least once a week). 11. High levels of non-recreational exercise (> 6h per week of high-intensity exercise or sport). 12. Fat Mass Index (FMI) 10 kg/m² (Men) and 12 kg/m² (Women). 13. Known negative reaction to lidocaine anaesthetic and/or taking warfarin. 14. Not weight stable in the prior 3 months (> 5% weight change). 15. Unable to converse in English.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Skeletal muscle (synthesis and breakdown) and whole-body (oxidation and net balance) protein metabolism measured using Stable Isotope Tracers over 3 hours (Older people only - Visit 3). 2. Adipose tissue expression and secretion of cytokines and adipokines in older people and younger adults in the post-absorptive state measured using RNAseq, multiplex antibody-based assays and/or proteomics from biopsies collected at visit 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Adipose tissue immune cell phenotype, function and activation in the post-adbsorptive state measured using spectral flow cytometry from biopsies collected at Visit 2 (All) 2. Single-cell RNA sequencing of adipose stromavascular fraction (non-adipocytes) in the post-absorptive state from biopsies collected at Visit 2 (subset of participants). 3. Measures of muscle protein metabolism and development (diameter) in skeletal muscle cell models when cultured in vitro with adipose explant media and serum from young and old participants collected at Visit 2. 4. Concentrations of cytokines and adipokines in human serum collected in the post-absorptive state, measured using antibody-based electro-chemiluminescence from blood samples collected at Visit 2 (All). 5. Skeletal muscle gene expression before and after the resistance exercise protocol in Visit 3 measured using PCR (Older only). 6. Skeletal muscle gene expression before and after ingestion of protein beverage in Visit 3 measured using PCR (Older only). 7. Post-prandial change in plasma glucose over 2 hours measured using a clinical metabolite analyser (Visit 2 - All). 8. Post-prandial change in plasma insulin over 2 hours measured using enzyme-linked immunosorbent assay (Visit 2 - All). 9. Postprandial change in plasma non-esterified fatty acids (NEFA) over 2 hours measured using a clinical metabolite analyser (Visit 2 - All). 10. Postprandial change in plasma glycerol over 2 hours measured using a clinical metabolite analyser (Visit 2 - All) 11. Postprandial change in energy expenditure over 2 hours measured using indirect calorimetry (Visit 2 - All). 12. Postprandial change in substrate oxidation measured using indirect calorimetry (Visit 2 - All). 13. Physical activity energy expenditure measured using combined accelerometry and heart rate. 14. Energy intake measured using weighed food record over 3 days between Visit 1 and Visit 2. 15. Subjective sleep quality measured using the Pittsburgh Sleep Quality Index ( | — |
Countries
England, United Kingdom