Completed Bones, Joints & Muscles NIHR-supported project Diabetes, Hormones & Metabolism

Using Biomarkers of Ageing to understand Sarcopenia and the Relationships with Inactivity, Depressive symptoms and Exhaustion in people living with Multiple Long Term Conditions – a proof of concept study

Funder NIHR (part of DHSC)
Recipient organisation NIHR Wellcome Trust Newcastle Clinical Research Facility
NIHR support Recorded as supported by this research centre
Period Jan 2025 — Apr 2026

In plain English

AI plain-English summary

People living with multiple long-term conditions often have low muscle strength, fatigue, and low mood—yet these problems are usually treated separately rather than as linked symptoms of a shared biological process. This matters because the current approach misses an opportunity. The biological mechanisms of ageing—the same ones that drive many long-term conditions—are also implicated in muscle weakness, exhaustion, and depression. Previous studies have examined these relationships in isolation, failing to capture how they interact with physical inactivity to worsen health. This proof-of-concept study will test whether an interdisciplinary systems approach can reveal the shared biological underpinnings of sarcopenia, fatigue, low mood, and inactivity in people with multiple conditions. If successful, this work could open the door to treatments that tackle all of these issues together, rather than piecemeal. That would be a practical shift for patients who currently cycle between specialists for separate problems. It could also reshape how clinicians assess and manage multimorbidity, moving from symptom-by-symptom care toward interventions that target the fundamental ageing processes driving multiple conditions at once.

View original technical description
People living with multiple long-term conditions (MLTCs), sometimes referred to as multimorbidity, report poorer quality of life and greater difficulties with activities of daily living than age matched controls with single organ disease. Importantly, they are also more likely to have low muscle strength (sarcopenia), fatigue or low mood. These interlinked problems contribute to low levels of physical activity, which compounds both the presence and progression of MLTC but can also worsen strength, fatigue and mood. Biological mechanisms that underpin ageing (the geroscience paradigm) are linked to the development of many long-term conditions. These mechanisms are also implicated in the development of muscle weakness, fatigue and low mood. Previous studies have examined these relationships in isolation, missing an opportunity to understand the complexity of the interaction between ageing and MLTC on the one hand, and weakness, fatigue, low mood and physical activity on the other hand. Understanding the biological mechanisms underlying depression, fatigue, sarcopenia and reduced activity in MLTC may offer novel treatment targets that enable all of these issues to be tackled together, rather than separately. This proof-of-concept study will demonstrate the feasibility of an interdisciplinary systems approach to this challenge.

Researchers

Miles Witham (Principal Investigator)

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