Impact of Ageing on Adipose, Muscle and Systemic Inflammation
1 other identifier
observational
24
1 country
1
Brief Summary
The accumulation and dysfunction of excess adipose (fat) tissue that occurs with ageing is associated with a number of chronic inflammatory disorders such as type 2 diabetes and cardiovascular disease but the underlying mechanisms are not understood.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started May 2016
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2016
CompletedFirst Submitted
Initial submission to the registry
May 6, 2016
CompletedFirst Posted
Study publicly available on registry
May 19, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2018
CompletedAugust 24, 2018
August 1, 2018
1.8 years
May 6, 2016
August 22, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Differences in immune cell populations (macrophages/Tcells) in adipose tissue of young versus old males
through to study completion, an average of 14 months
Secondary Outcomes (5)
the impact of ageing on mRNA expression of key metabolic and inflammatory genes in adipose tissue.
through to study completion, an average of 14 months
the impact of ageing on metabolic and inflammatory protein secretions (into culture media) from adipose tissue
through to study completion, an average of 14 months
differences in immune cell populations in muscle tissue and blood compared to adipose tissue from the same individuals and the impact of ageing on immune cell populations in muscle tissue.
through to study completion, an average of 14 months
the impact of ageing on mRNA expression of other key metabolic and inflammatory genes in muscle tissue.
through to study completion, an average of 14 months
activation/inhibition of e.g. insulin stimulated pathways in adipose and muscle tissues (for example assessment of Akt/IRS1 phosphorylation by western blot analysis).
through to study completion, an average of 14 months
Study Arms (2)
Young males aged 20-35 years old
Maintaining a normal daily living lifestyle * Healthy * Reasonably active- PAL: 1.4-1.9 * Non-obese- Fat mass index based on DEXA of 4-8kg/m2 * Weight stable for more than 3 months (±3% body mass) * Non-smoker * No chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders * No daily consumption of analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription * No medications that may influence lipid or carbohydrate metabolism or immune system function * No known negative reaction to lidocaine * No participation in heavy resistance training
Old males aged 65-85 years old
Maintaining a normal daily living lifestyle * Healthy * Reasonably active- PAL: 1.4-1.9 * Non-obese- Fat mass index based on DEXA of 4-8kg/m2 * Weight stable for more than 3 months (±3% body mass) * Non-smoker * No chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders * No daily consumption of analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription * No medications that may influence lipid or carbohydrate metabolism or immune system function * No known negative reaction to lidocaine * No participation in heavy resistance training
Interventions
participants will undertake a normal lifestyle with no alterations to daily living in order to access the differences in tissue (muscle and adipose) and systemic inflammation between the two age cohorts
Eligibility Criteria
general free-living public in the Bath and the surrounding areas
You may qualify if:
- Male
- Aged between 20-35 years (Group 1) or 65-85 years (Group 2)
- Fat mass index based on DEXA between 4-8 kg/m2
- Weight stable for more than 3 months (no change in weight +/- 3%)
- Physical Activity Level (PAL) between 1.4 and 1.9
- Non-smoker
- Healthy
You may not qualify if:
- Any chronic illness, cardiac, pulmonary, liver, or kidney abnormalities, uncontrolled hypertension, peripheral arterial disease, insulin- or non-insulin dependent diabetes or other metabolic disorders
- Individuals who consume on a daily basis any analgesic or anti-inflammatory drug(s) including NSAIDs and corticosteroids, prescription or non-prescription
- Taking any medications that may influence lipid or carbohydrate metabolism or immune system function
- Individuals with a known negative reaction to lidocaine anaesthetic
- Participation in heavy resistance training
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
university of bath - Department for Health
Bath, Somerset, BA2 7AY, United Kingdom
Related Publications (20)
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PMID: 24849392BACKGROUNDBourlier V, Zakaroff-Girard A, Miranville A, De Barros S, Maumus M, Sengenes C, Galitzky J, Lafontan M, Karpe F, Frayn KN, Bouloumie A. Remodeling phenotype of human subcutaneous adipose tissue macrophages. Circulation. 2008 Feb 12;117(6):806-15. doi: 10.1161/CIRCULATIONAHA.107.724096. Epub 2008 Jan 28.
PMID: 18227385BACKGROUNDCancello R, Tordjman J, Poitou C, Guilhem G, Bouillot JL, Hugol D, Coussieu C, Basdevant A, Bar Hen A, Bedossa P, Guerre-Millo M, Clement K. Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity. Diabetes. 2006 Jun;55(6):1554-61. doi: 10.2337/db06-0133.
PMID: 16731817BACKGROUNDClement K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, Sicard A, Rome S, Benis A, Zucker JD, Vidal H, Laville M, Barsh GS, Basdevant A, Stich V, Cancello R, Langin D. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J. 2004 Nov;18(14):1657-69. doi: 10.1096/fj.04-2204com.
PMID: 15522911BACKGROUNDCurat CA, Miranville A, Sengenes C, Diehl M, Tonus C, Busse R, Bouloumie A. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes. 2004 May;53(5):1285-92. doi: 10.2337/diabetes.53.5.1285.
PMID: 15111498BACKGROUNDDyck DJ, Heigenhauser GJ, Bruce CR. The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity. Acta Physiol (Oxf). 2006 Jan;186(1):5-16. doi: 10.1111/j.1748-1716.2005.01502.x.
PMID: 16497175BACKGROUNDFabbrini E, Cella M, McCartney SA, Fuchs A, Abumrad NA, Pietka TA, Chen Z, Finck BN, Han DH, Magkos F, Conte C, Bradley D, Fraterrigo G, Eagon JC, Patterson BW, Colonna M, Klein S. Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013 Aug;145(2):366-74.e1-3. doi: 10.1053/j.gastro.2013.04.010. Epub 2013 Apr 15.
PMID: 23597726BACKGROUNDFantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005 May;115(5):911-9; quiz 920. doi: 10.1016/j.jaci.2005.02.023.
PMID: 15867843BACKGROUNDGoossens GH, Blaak EE, Theunissen R, Duijvestijn AM, Clement K, Tervaert JW, Thewissen MM. Expression of NLRP3 inflammasome and T cell population markers in adipose tissue are associated with insulin resistance and impaired glucose metabolism in humans. Mol Immunol. 2012 Mar;50(3):142-9. doi: 10.1016/j.molimm.2012.01.005. Epub 2012 Feb 8.
PMID: 22325453BACKGROUNDLumeng CN, Liu J, Geletka L, Delaney C, Delproposto J, Desai A, Oatmen K, Martinez-Santibanez G, Julius A, Garg S, Yung RL. Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue. J Immunol. 2011 Dec 15;187(12):6208-16. doi: 10.4049/jimmunol.1102188. Epub 2011 Nov 9.
PMID: 22075699BACKGROUNDNishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009 Aug;15(8):914-20. doi: 10.1038/nm.1964. Epub 2009 Jul 26.
PMID: 19633658BACKGROUNDOrtega Martinez de Victoria E, Xu X, Koska J, Francisco AM, Scalise M, Ferrante AW Jr, Krakoff J. Macrophage content in subcutaneous adipose tissue: associations with adiposity, age, inflammatory markers, and whole-body insulin action in healthy Pima Indians. Diabetes. 2009 Feb;58(2):385-93. doi: 10.2337/db08-0536. Epub 2008 Nov 13.
PMID: 19008342BACKGROUNDPararasa C, Bailey CJ, Griffiths HR. Ageing, adipose tissue, fatty acids and inflammation. Biogerontology. 2015 Apr;16(2):235-48. doi: 10.1007/s10522-014-9536-x. Epub 2014 Nov 4.
PMID: 25367746BACKGROUNDThompson D, Karpe F, Lafontan M, Frayn K. Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol Rev. 2012 Jan;92(1):157-91. doi: 10.1152/physrev.00012.2011.
PMID: 22298655BACKGROUNDTravers RL, Motta AC, Betts JA, Bouloumie A, Thompson D. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans. Int J Obes (Lond). 2015 May;39(5):762-9. doi: 10.1038/ijo.2014.195. Epub 2014 Nov 12.
PMID: 25388403BACKGROUNDTrayhurn P, Drevon CA, Eckel J. Secreted proteins from adipose tissue and skeletal muscle - adipokines, myokines and adipose/muscle cross-talk. Arch Physiol Biochem. 2011 May;117(2):47-56. doi: 10.3109/13813455.2010.535835. Epub 2010 Dec 15.
PMID: 21158485BACKGROUNDVarma V, Yao-Borengasser A, Rasouli N, Nolen GT, Phanavanh B, Starks T, Gurley C, Simpson P, McGehee RE Jr, Kern PA, Peterson CA. Muscle inflammatory response and insulin resistance: synergistic interaction between macrophages and fatty acids leads to impaired insulin action. Am J Physiol Endocrinol Metab. 2009 Jun;296(6):E1300-10. doi: 10.1152/ajpendo.90885.2008. Epub 2009 Mar 31.
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PMID: 14679176BACKGROUNDZeyda M, Farmer D, Todoric J, Aszmann O, Speiser M, Gyori G, Zlabinger GJ, Stulnig TM. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes (Lond). 2007 Sep;31(9):1420-8. doi: 10.1038/sj.ijo.0803632. Epub 2007 Jun 26.
PMID: 17593905BACKGROUNDXu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003 Dec;112(12):1821-30. doi: 10.1172/JCI19451.
PMID: 14679177BACKGROUND
Biospecimen
muscle and adipose biopsies blood plasma blood serum peripheral blood mononuclear cells
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dylan Thompson, Professor
University of Bath
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Ph.D. Student
Study Record Dates
First Submitted
May 6, 2016
First Posted
May 19, 2016
Study Start
May 1, 2016
Primary Completion
March 1, 2018
Study Completion
October 1, 2018
Last Updated
August 24, 2018
Record last verified: 2018-08
Data Sharing
- IPD Sharing
- Will share