There are many, many factors that we are exposed to during our lifetime that can affect our lifespan. These include our genetics and many other environmental factors such as diet or medication and so on. But whether these factors impact our healthspan – the time we spend as a healthy individual – is not as clear cut. With our population becoming older, there is an urgent need to find ways to maintain our healthspan for longer, but a major challenge in age-related research is that there aren’t many well-defined characteristics of healthspan, and so we routinely use well known signs of ageing instead. However, it is evident that prolonged lifespan does not always link up with an extended healthspan. Therefore, the search for techniques and markers that can measure effects on healthspan is a necessity, so that we can also test drugs and interventions to try and extend healthspan too.

Research published on 25 February in Nature Communications by our Host Microbe Co-Metabolism group has shown how healthspan biomarkers can be measured using a technique called Atomic Force Microscopy.

Biomechanics of a cell, such as their ability to move and have structure, are linked to key processes. Cells are always under constant pressure from their neighbouring cells, being confined to space or from contractile stress which is key to normal function. So, it is perhaps no surprise to know that dysregulation of these biomechanical processes can lead to alterations in physiology, and introduce disease states, but also the decay of these processes during ageing may underlie these pathologies.

Using the model organism, the C. elegans worm, our colleagues captured highly detailed images of the worm’s cuticle – the equivalent to our skin – and performed highly sensitive stiffness measurements – the equivalent of our tissues to withstand external pressure, during ageing. Like in humans, where wrinkles imply old age and the skin hangs loosely, in old worms, both the quality of the cuticle and stiffness of the worm decreased with age. However, when worms were subjected to different diets, drugs and alterations to their genetics that could increase lifespan, not all the parameters lead to an extended healthspan too. This suggests that many interventions and tests are needed to understand if changing certain factors, like diet or drugs, may increase healthspan as well as lifespan in order to improve ageing. Ultimately, the work implies that for healthy ageing we may need separate interventions; one to increase our longevity, and one to make sure we stay healthier for longer.

Clara Essmann, first author of this paper, discussed the findings of this paper:

“These results were really rewarding because we get to see how the worms actually look and measure whether they are fit or not by putting a number to it. Furthermore, adding drugs and assessing their effects on healthspan and lifespan is easier when you can put a number to it. This method of Atomic Force Microscopy can allow us to do that at much higher resolution that before and give us insights that other techniques just would not have been able to pick up. We don’t want to live a long time and be sick. We want most of our lives to be healthy. Using this technique to find further cues and biomarkers will give us hints to how genetics and drugs may be helping.”

Filipe Cabreiro, Head of the Host Microbe Co-Metabolism group discussed this opportunity and next steps for the work:

“The beauty of this opportunity was to combine high-end microscopy with ageing C. elegans research. I saw Clara speak at a conference and knew that through a collaboration we could start to work towards answering key questions related to health during the ageing process. It is crucial to knowing how we can adapt the interventions best to maximise health and longevity. Our next steps for this work would be to try and develop methods to measure this in a high-throughput way, and test hundreds of conditions simultaneously.”

‘Mechanical properties measured by Atomic Force Microscopy define health biomarkers in ageing C.elegans’ was published on 25 February in Nature Communications. Read the article here.