Projects per year
Abstract
Key points: Ageing is associated with increased systemic inflammation and metabolic dysfunction that contributes to the development of age-associated diseases. The role of adipose tissue in immunometabolic alterations that take place with ageing is unknown in humans. We show, in healthy, active and lean older adults, that adipose tissue, but not skeletal muscle, displays considerable pro-inflammatory transcriptomic, cellular and secretory changes, as well as a reduction in insulin signalling proteins compared to younger adults. These findings indicate that adipose tissue undergoes substantial immunometabolic alterations with ageing, and that these changes are tissue-specific and more profound than those observed in skeletal muscle or in the circulation. These results identify adipose tissue as an important tissue in the biological ageing process in humans, which may exhibit signs of immunometabolic dysfunction prior to systemic manifestation. Abstract: Ageing and obesity are both characterized by inflammation and a deterioration in metabolic health. It is now clear that adipose tissue plays a major role in inflammation and metabolic control in obesity, although little is known about the role of adipose tissue in human ageing. To understand how ageing impacts adipose tissue, we characterized subcutaneous adipose tissue and skeletal muscle samples from twelve younger (27 ± 4 years [Young]) and twelve older (66 ± 5 years [Old]) active/non-obese males. We performed a wide-range of whole-body and tissue measures, including RNA-sequencing and multicolour flow cytometry. We also measured a range of inflammatory and metabolic proteins in the circulation and their release by adipose tissue, ex vivo. Both adipose tissue and muscle had ∼2-fold more immune cells per gram of tissue with ageing. In adipose tissue, this immune cell infiltration was driven by increased memory/effector T-cells, whereas, in muscle, the accumulation was driven by memory/effector T-cells and macrophages. Transcriptomic analysis revealed that, with ageing, adipose tissue, but not muscle, was enriched for inflammatory transcripts/pathways related to acquired and innate immunity. Ageing also increased the adipose tissue pro-inflammatory secretory profile. Insulin signalling protein content was reduced in adipose tissue, but not muscle. Our findings indicate that adipose tissue undergoes substantial immunometabolic changes with ageing in humans, and that these changes are tissue-specific and more profound than those observed in the circulation and skeletal muscle.
Original language | English |
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Pages (from-to) | 921-947 |
Number of pages | 27 |
Journal | The Journal of Physiology |
Volume | 600 |
Issue number | 4 |
Early online date | 24 Apr 2021 |
DOIs | |
Publication status | Published - 15 Feb 2022 |
Keywords
- adipose tissue
- ageing
- immunometabolism
- inflammation
- metabolism
- skeletal muscle
ASJC Scopus subject areas
- Physiology
Fingerprint
Dive into the research topics of 'Divergent immunometabolic changes in adipose tissue and skeletal muscle with ageing in healthy humans'. Together they form a unique fingerprint.Projects
- 2 Finished
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Role of Rab3 in Peripheral Tissue Insulin Resistance
Koumanov, F., Betts, J., Gonzalez, J., Thompson, D. & Whitley, P.
1/12/16 → 31/07/20
Project: Research council
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Targeting Bed Reset-Induced Adipose Tissue Dysfunction with Anti-Inflammatory and Antioxidant Nutrients
Thompson, D., Holman, G., Stokes, K. & Turner, J.
Biotechnology and Biological Sciences Research Council
1/07/15 → 30/06/19
Project: Research council
Datasets
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Dataset for "Divergent immunometabolic changes in adipose tissue and skeletal muscle with ageing in healthy humans"
Trim, W. (Creator), Walhin, J. (Creator), Koumanov, F. (Creator), Bouloumié, A. (Creator), Lindsay, M. (Creator), Chen, Y. (Creator), Travers, R. (Creator), Turner, J. (Creator) & Thompson, D. (Creator), University of Bath, 24 Apr 2021
DOI: 10.15125/BATH-00806
Dataset