PhD Perspectives: Understanding muscle loss in inflammatory disease

My name is Ana Crastin, and I am a third-year PhD student researching how inflammatory macrophage steroid metabolism drives muscle wasting in inflammatory diseases.

Before starting my PhD, I worked in a role that introduced me to the complexity and importance of endocrine regulation in the human body. I became fascinated by how hormones influence almost every aspect of our health, and by how much we still do not understand about the ways disease can disrupt these systems.

When I began researching steroid regulation in inflammatory disease, my father was diagnosed with osteoarthritis. That experience made the realities faced by patients with chronic inflammatory conditions much more personal to me and strengthened my motivation to contribute to this area of research.

Investigating why muscle loss happens

My PhD project focuses on understanding how changes in macrophage steroid metabolism during inflammatory disease contribute to skeletal muscle wasting.

Macrophages are immune cells that help regulate inflammation in the body. During inflammatory disease, these cells alter the way they process steroid hormones, and we believe this change may negatively affect muscle regeneration and maintenance.

Importantly, the same biological mechanisms we observe in inflammatory disease are also linked to healthy ageing and sarcopenia – the progressive loss of muscle mass and strength that occurs with age.

Our long-term aim is to identify ways to therapeutically target this abnormal macrophage steroid metabolism to prevent or reduce muscle loss.

This matters because skeletal muscle is far more than just the tissue that allows us to move. It is also a vital metabolic organ involved in regulating blood sugar levels and overall energy balance. When people lose muscle mass, they become more vulnerable to conditions such as diabetes, cardiovascular disease, frailty, and loss of independence.

Why this research matters

Maintaining skeletal muscle is essential for preserving mobility, strength, and quality of life.

As people age or live with chronic inflammatory disease, muscle loss can become disabling. Patients may struggle with everyday activities, recover more slowly from illness, and become increasingly frail. This not only affects lifespan, but also “healthspan” – the number of years spent living in good health.

By understanding the biological mechanisms driving muscle loss, we hope to develop strategies that could help patients remain healthier and more independent for longer. In the future, this could also help reduce pressure on healthcare services by preventing complications associated with frailty and chronic disease.

My research approach

In the lab, I work with cells donated by patients with inflammatory disease. From these samples, I grow skeletal muscle cells and isolate macrophages, a key type of immune cell involved in inflammation.

I then induce the macrophages into an inflammatory state and treat them with steroid hormones. The macrophages activate these hormones through their metabolism, and I collect the resulting macrophage-conditioned media and apply it to muscle cells.

Using this approach, I investigate how inflammatory macrophages affect muscle cell growth, protein metabolism, differentiation into mature muscle fibres, and energy metabolism.

A major part of my work involves testing whether blocking the macrophages’ ability to activate these hormones can reverse the harmful effects on muscle cells. To do this, I use metabolic inhibitors that target specific pathways involved in steroid activation.

Although the science is complex, the central question is simple: can we stop inflammatory immune cells from driving muscle loss?

What excites me most

One of the most exciting parts of my research has been seeing encouraging preliminary results in patient-derived cell cultures.

So far, we have observed that inhibiting hormone activation in inflammatory macrophages appears to reverse some of the negative effects on muscle regeneration and metabolism. These findings suggest that this pathway could become a promising therapeutic target for both patients with inflammatory disease and potentially the ageing population more broadly.

Knowing that our work could one day contribute to improving quality of life for patients is incredibly motivating.

My experience as a BRC PhD student

Being part of the BRC has provided me with fantastic opportunities to grow as a researcher beyond the laboratory.

I have attended the NIHR Applying for Funding Training Camp, participated in the Student-Patient Alliance Scheme, and I am currently involved in developing a student animation project related to my BRC theme.

The BRC environment has also connected me with researchers across Birmingham working in a wide range of disciplines and specialities. These collaborations and networks have helped broaden my perspective and encouraged interdisciplinary research approaches.

Looking ahead

Our ultimate aspiration is to translate this research into clinical trials, provided our findings continue to show strong potential by the end of my PhD.

As populations continue to age, finding ways to help people remain healthier for longer is becoming increasingly important. We believe that preserving skeletal muscle could play a major role in improving long-term health, independence, and resilience in both inflammatory disease and ageing.

I hope this research will contribute to developing treatments that not only extend lifespan but also improve the quality of those years for patients.