Monday, 22 August 2016

Tissue "archeology": Dating collagen fibers

ISTM recently ran a blog writing competition that was open to PhD students and young researchers with a view to improving their lay-writing skills and helping ISTM to play a greater role in the public dissemination of its research. After concluding the competition we will be publishing each entry in turn over the coming months. The 2nd prize winner of our competition was Homayemem Weli, a PhD student in Cell and Tissue Engineering at ISTM. 


Walking through the streets of London in mid-summer, I couldn’t help but notice its beautiful 'ornaments' of modern architecture, such as the "Gherkin" or the "Walkie-Talkie". Imposing as these are, they attract less curiosity than Wiltshire’s Stonehenge.

A graceful and strong modern building speaks of a firm foundation and good design, but an ancient monument raises questions such as "when", "how" and "why". Some of us recall the creation of the London skyscrapers - having possibly witnessed it - but I dare say none of us witnessed the making of Stonehenge! Instead, we rely on archaeological research to answer questions about its origin, age and significance. This ‘discovery science’ compels us to find out why things are the way they are, and go from the known to the unknown.

Stonehenge by David Ball -

Keen to unravel the unknown, I set out to study an aspect of why people age. My focus was on women and what happens to their vaginal and skin tissues before and after pregnancy. Adorned with laboratory clothing and gloves, as though performing carbon dating on the standing stones of Stonehenge, I examined the structure of collagen fibres and cross-links within the tissues. Collagen is a protein that supports structures within the body. Cross-links are bonds formed between collagen groups (called fibres) or between chemical substances such as amino acids or reducing sugars. The larger the number of certain cross-links within the collagen fibres, the older the fibres. Collagen 'cross-link dating' can separate old fibres from young ones.

I tested two groups of tissues, pregnant and non-pregnant, of similar biological ages. I separated a particular cross-link, pentosidine, which is a known marker of tissue ageing, from the tissue solutions with liquid chromatography (a method for identifying and separating substances present within a solution). I noted the amount of pentosidine in each tissue, and compared the values.

This process of 'cross-link dating' separated the age-matched tissues into two groups – ‘old’ and ‘young’. Before pregnancy, tissues were ‘older’, but after pregnancy, they appeared ‘younger’. During pregnancy, the signs of ageing appeared to reverse! 

Studying further, I discovered this was linked with a rise of a potent antioxidant, glyoxalase I, in the tissues during pregnancy. Antioxidants such as glyoxalase I protect the body cells from molecules that could cause damage or promote ageing.

Antioxidant glyoxalase I enzyme expression in vaginal tissues during (left) and after (right) pregnancy. Green glow, clearly visible within the pregnant tissue, represents presence of the antioxidant enzyme. The pregnant tissues had more antioxidant. 

Oestrogen, a well-known pregnancy hormone, influenced the amount of the antioxidant in the tissues. I found higher oestrogen levels in pregnant tissues as shown in the images below. This implied pregnancy resulted in higher oestrogen and antioxidant levels.

Oestrogen receptor expression in vaginal tissues during (left) and after (right) pregnancy. Red dots signify oestrogen activity within the tissue and show raised level of oestrogen during pregnancy.

I concluded that oestrogen influences the ‘age’ of collagen fibres of the skin and vaginal wall by increasing the antioxidant glyoxalase I. Rise in oestrogen as seen in pregnancy leads to rise in the enzyme, subsequently retarding collagen fibre ageing within the tissues. In this way, pregnancy results in younger appearing tissues.

Oestrogen is a female reproductive hormone that changes throughout the life of a woman. It increases in quantity during pregnancy and reduces as women grow older, finally reaching its lowest levels in menopause. My finding shows that pregnancy may retard this ageing process in the vaginal and skin tissues of women. A previous study noted a reduction in similar ageing cross-links within blood vessels also in association with higher oestrogen levels, suggesting that this effect may exist in many body tissues.

By studying pregnancy, I discovered a relationship between oestrogen, an antioxidant, and the ‘age’ of collagen fibres (change of the structure) in skin and vaginal tissues.

New knowledge can be gained from investigating age-old body processes. It's always worth asking "when", "how" and "why”!

Written by Homayemem Weli, PhD Student, ISTM
(2nd Prize in the ISTM Blog Post Competition 2016)

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