Quantifying Age-related Changes in the Mechanical Properties of Tissues

As people get older the mechanical properties of the body change and many components of the cardiovascular system become stiffer. Stiffening of the arteries has been implicated in increased mortality from heart failure, stroke and aneurysms. Arterial stiffening can also occur through the action of other age-related conditions, e.g. raised blood pressure, diabetes and kidney failure. Collectively, these failures of the cardiovascular system are the most common cause of death in the western world. Other tissues within the body can also deteriorate with time and although not life threatening, can seriously affect the quality of life, e.g. debilitating lower back pain is associated with the mechanical deterioration of the intervertebral disc. Cosmetic changes with age are also important for personal well being and the global market in anti-ageing treatments is forecast to exceed $250 billion by 2015; development of such personal care products is an important part of the British economy. Thus understanding how the ageing process leads to the stiffening of tissue is important in improving life expectancy and importantly, improving the well being of the population as a greater proportion of the population is living longer.
One obstacle to our understanding of how ageing changes the mechanical properties of tissue is the relatively primitive methods currently used to measure them. These were originally developed to measure the properties of engineering materials such as metals and polymers; these are much stiffer than biological materials and are simpler in composition. However, recent developments in mechanical testing methods allow us to now use a technique called nanoindentation that can be used to measure the mechanical properties, not only of tissue but also of the microscopic components that cause the changes in properties with age. By further developing this new technique we will be able to explore how changes in these components that occur during ageing, which can be monitored using microscope observation, degrade the stiffness and other mechanical properties. Because the volumes of material sampled are so small, the technique will allow us to measure the properties of human tissue using a minimally invasive approach. This can then be used to monitor the progress of ageing and chronic disease and any treatment used to alleviate symptoms.

Age-related changes in the mechanical properties of dynamic tissues within the pulmonary, cardiovascular and musculoskeletal systems profoundly affect human morbidity and mortality. Despite the immense clinical and economic burdens that result from disorders such as hypertension and low back pain, to date attempts to identify and localize the key molecular mechanisms which cause age-related loss of tissue compliance and elastic recoil have been limited by inadequate methods for measuring local mechanical properties of tissue. Therefore, we will develop nanoindentation techniques to map and quantify micrometer-scale changes in tissue mechanical properties to individual tissue components.

Nanoindentation is routinely used in materials science to measure the mechanical properties of small volumes of engineering materials, with micrometre spatial resolution. Using this technique, we will determine how age-related changes in the structure of soft tissue cryo-sections influence local changes in mechanical properties and hence understand the mechanisms that lead to changes in bulk tissue behaviour. To achieve this we have specified a modified commercial nanoindentation platform, to include a high quality optical microscope that utilizes molecular auto-fluorescence and differential interference contrast to identify and then quantify the micromechanical properties of discrete tissue structures. Although we have successfully used nanoindentation to characterize tissue mechanical properties in Manchester, further development of the technique will be undertaken to develop constitutive laws that describe tissue mechanical behaviour and link it to tissue microstructure.

In order to achieve these goals we have assembled a multidisciplinary team of materials scientists, life scientists and clinicians to apply this technique to research projects in three organ system where age-related mechanical change profoundly affect human mortality, morbidity and well-being. These are: 1) the increase in stiffness of the vasculature that occurs during both ageing and age-related disorders such as diabetes; 2) age-related degeneration of the intervertebral disc which is associated with low back pain; and 3) commercially important changes in the mechanical properties of ageing skin. A further advantage of the technology, is that by developing its use with standard histological specimens, we can provide mechanical analysis using very small quantities of tissue samples consistent with minimally invasive biopsies. Once these techniques are established and validated we will disseminate the details via scientific publications and invite the wider research community to utilise the approach.