Theme 1: Molecular and Metabolic Signatures in Sarcopenic Muscle of the MAGNET Cohort

Uncovering the molecular differences that shape how sarcopenia develops, progresses and responds to treatment.

Theme Lead: Professor Teh Bin Tean, NCCS

Co-Leads: Associate Professor Chen Jinmiao and Dr Guan Pei Yong, GIS

Understanding Sarcopenia at the Molecular Level

Sarcopenia does not affect everyone in the same way.

Theme 1 investigates the molecular and metabolic changes within muscle to understand why the condition develops and progresses differently between individuals.

By studying gene activity, individual cells, signalling pathways and metabolism, our researchers aim to identify distinct biological signatures that could enable earlier diagnosis, better patient stratification and new therapeutic approaches.

Molecular Signatures

Identify patterns of gene activity associated with different stages and subtypes of sarcopenia.

Cellular Changes

Understand disease mechanisms from individual cells through to whole muscle tissue.

Muscle Metabolism

Discover how nutrient and energy metabolism changes as sarcopenia develops.

What We've Discovered

Sarcopenia may have distinct molecular subtypes.

Our studies provide the first evidence that sarcopenia may comprise at least four distinct molecular states (G1-G4), based on differences in gene activity within muscle.

These findings could help explain why the condition develops differently between individuals and why responses to treatment may vary.

200+ Participants Profiled.

Mapping gene activity across sarcopenia.

Using muscle samples from the MAGNET biorepository, researchers are conducting transcriptomic profiling in an initial discovery cohort of more than 200 participants. By examining patterns of gene activity, the team aims to identify biological signatures associated with different stages and subtypes of sarcopenia.

Potential impact: Earlier diagnostic biomarkers and a better understanding of disease progression.

6 Patients studied at single-cell level.

Understanding sarcopenia cell by cell.

MAGNET has performed single-cell profiling on muscle samples from six patients with sarcopenia, allowing researchers to investigate disease-related changes at the level of individual cells. This provides a deeper understanding of the cellular and molecular changes that may drive the development and progression of sarcopenia.

Potential impact: Identification of key disease mechanisms and potential targets for future treatments.

Building a Molecular Atlas of Sarcopenia

Connecting molecular discovery to earlier diagnosis and new therapeutic opportunities.

Theme 1 aims to build a detailed molecular atlas of sarcopenia, mapping the molecular and metabolic changes that occur as the disease develops and progresses.

By uncovering these biological signatures and pathways, Theme 1 will provide a foundation for research across the wider MAGNET programme.

Enabling Earlier Detection -
Supporting Theme 2

Molecular signatures identified in Theme 1 will help guide the discovery of biomarkers for earlier detection, including at the potentially reversible pre-sarcopenic stage - creating opportunities for earlier intervention.

Identifying New Therapeutic Targets -
Supporting Theme 3

Theme 1 will identify key molecular and metabolic pathways involved in sarcopenia development and progression, providing promising mechanisms and therapeutic targets for further investigation and validation.

Building Our Data Together with AI

Connecting molecular and clinical data to unlock deeper insights into sarcopenia.

MAGNET will generate a wealth of molecular and clinical data across the programme. MAGNET*AI and MAGNET*Hub will work together to integrate, analyse and organise these data - helping researchers build a more comprehensive picture of sarcopenia and how it differs between individuals.

**MAGNET*AI**

Turning complex data into meaningful insights.

Developed specifically for MAGNET, MAGNET*AI will integrate and analyse different types of molecular and clinical data to better understand each individual's disease profile.

It will help researchers to:

Distinguish between healthy and diseased states
Track sarcopenia progression
Identify different patient groups
Predict responses to treatment
Discover new biological signatures, including genes, proteins and metabolites

**MAGNET*Hub**

Connecting MAGNET's research data.

MAGNET*Hub will bring together and harmonise molecular profiling data and clinical measurements generated across the programme into a structured, shareable resource.

Hosted as part of the DISCO data hub, MAGNET*Hub will serve as a central data resource, enabling researchers to connect findings across studies and make better use of MAGNET's growing wealth of research data.