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New research from the Kennedy Institute of Rheumatology (Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences) identifies vascular attrition, marked by pericyte to fibroblast differentiation, as a primary hallmark of ageing and highlights organ-specific vascular changes with age.

A montage of images showing 3D scans of mouse spleens and kidneys
From left to right 1 - Tile scan 3D confocal image showing a mouse spleen with multicolour immunolabeling for endothelial cell and pericyte markers. Blue shows cell nuclei stained with TO-PRO-3. 2 - Tile scan 3D confocal image showing a mouse spleen with multicolour immunolabeling for endothelial cell and pericyte markers. 3 - Tile scan 3D confocal image showing a mouse kidney with multicolour immunolabeling for endothelial cell and pericyte markers. Blue shows cell nuclei stained with TO-PRO-3. 4 - Tile scan 3D confocal image showing a mouse kidney with multicolour immunolabeling for endothelial cell and pericyte markers.

Cellular and physiological activity in the body declines over time with age, resulting in a loss of tissue and organ function and the potential risk of major health conditions such as cancer or cardiovascular disease. What is less understood are age-related changes in the tissue microenvironment such as the blood vessels.

Blood vessels are an essential component in maintaining tissue function not only because they form vital transport routes around the body, but also because blood vessels engage in signalling with neighbouring cells within the tissues thereby governing their behaviour. For example, blood vessels provide nurturing niches for stem/progenitor cells and regulate their stemness and fate. Therefore, any vascular changes have the potential to reveal microenvironmental triggers impacting the aging process.

For the study which appears in Science Advances Anjali Kusumbe’s group examined 1000’s of confocal images across several murine and human organs. “The cellular aspects of ageing have been extensively studied and we understand how they affect tissue function. Our goal was to understand age-related changes to blood vessels, the vascular system, by comparing young and ageing tissues from several organs through 3D imaging.” said Anjali.

3D imaging showed the vascular microenvironments of the kidney, muscle, spleen, thymus, liver, lung, uterus, heart, bladder, brain, skin, and the gut. By comparing young and ageing tissues from several organs the study revealed a loss of vascular abundance and differentiation of pericytes into fibroblasts as the key features of ageing tissue. Pericytes are the cells lining the blood vessels and support vascular functions while fibroblasts are known drivers for disease conditions such as fibrosis and arthritis.

Read the full story on the Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences website.

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