Summer and autumn meet in a city park, symbolising healthy ageing and the gradual changes that take place across the lifespan.
An international study maps gene changes in ageing mouse muscle, building on earlier work showing how ageing alters the extracellular matrix in tendons and skeletal muscle.
Ageing is often described through what we can see and feel: weaker muscles, reduced mobility and slower recovery. But behind these visible changes are deeper biological shifts in cells, tissues and the molecular structures that support them.
A recent study published in BMC Genomics offers a closer look at one of these hidden layers of ageing: the extracellular matrix, or ECM, in skeletal muscle. The ECM is the network of proteins and molecules that surrounds and supports cells. Once viewed mainly as passive scaffolding, it is now increasingly recognised as a dynamic part of tissue biology and an important feature of ageing.
In this study, an international collaborative team from INRAE, Université Clermont Auvergne, VetAgro Sup, Daegu Gyeongbuk Institute of Science and Technology, Nanyang Technological University, and Newcastle University in Singapore examined how gene expression changes in male mouse skeletal muscle across different stages of life.
The study compared muscle transcriptomic profiles from mice aged 2 months, 11 months and 25 months, representing young adult, mature adult and aged stages respectively. The aim was not simply to compare “young” and “old” animals, but to identify which biological changes are truly associated with ageing, rather than with normal maturation from youth to adulthood.
This distinction matters. Many ageing studies compare very young animals with old animals. However, the researchers found that many gene changes observed between 2 and 25 months were already present during maturation from 2 to 11 months. This means that a simple young-versus-old comparison may mix up two different biological processes: maturation and ageing.
The study suggests that, to better capture ageing-specific changes in male mice, researchers should compare aged animals with mature adult animals, rather than with very young animals. In practical terms, this means comparing old mice of around 20–22 months or older with mature adult mice of around 11 months. The authors note that these stages should be validated in female mice and in humans.
The new work builds on a series of earlier international studies involving some of the same researchers, including Kheng Lim Goh, that examined how ageing changes the extracellular matrix and the mechanical behaviour of connective tissues.
In a 2008 study on mouse tail tendons, researchers showed that age-related changes in tendon strength and stiffness were linked to the collagen fibril cross-sectional area fraction. Tendons were treated as biological fibre composites, with collagen fibrils reinforcing a proteoglycan-rich matrix. The study found that this structural measure was a significant predictor of ageing-related changes in tensile strength and stiffness.
A later 2012 study extended this structure–function view by examining how collagen fibril diameter distributions influence tendon mechanics across ageing. Rather than relying only on average fibril diameter, the study modelled tendon fibrils as two subpopulations. It showed that subtle shifts in these bimodal fibril populations helped explain age-related variation in tendon resilience and resistance to rupture.
The focus then moved from tendon mechanics to ageing skeletal muscle. In a 2014 study in Aging Cell, an international team including Huijuan Wang, Anne Listrat, Kijoon Lee, Kheng Lim Goh and Daniel Béchet showed that sarcopenia in mouse gastrocnemius muscle was associated with myofibre atrophy, oxidative fibre grouping, myonuclear delocalisation and extracellular matrix fibrosis. Importantly, the study found that much of the age-related increase in apoptosis occurred in stromal cells, especially capillary endothelial cells, rather than only in muscle fibre nuclei.
Together, these earlier studies pointed to a common message: ageing is not only a change in cells themselves, but also a change in the extracellular environment that supports, connects and regulates them. Tendons lose or alter mechanical resilience as collagen fibril organisation changes. Ageing muscle shows fibrosis, altered capillary function and changes in the connective tissue surrounding muscle fibres.
The 2026 BMC Genomics study takes this research programme to the molecular level. Instead of looking mainly at tissue mechanics, histology or cell death, it examines the transcriptome — the pattern of gene expression — to identify biological processes associated specifically with ageing muscle.
A central contribution of the study is its focus on the muscle “matrisome” — the full set of genes and proteins associated with the extracellular matrix. The researchers introduced the first transcriptomic “matreotype” of muscle ageing in a mammal. A matreotype refers to the ageing-associated composition of the matrisome.
The ageing muscle matreotype identified in the study consisted of 58 genes, 95% of which were downregulated. This suggests that ageing is associated not only with changes in muscle fibres themselves, but also with coordinated changes in the molecular environment that supports muscle structure, communication and repair.
The findings point to several biological processes involved in muscle ageing, including structural remodelling, changes in synaptic transmission, reduced extracellular matrix and angiogenesis-related processes, and increased apoptotic processes linked to the ECM. The study also identified transcription factors that may help regulate these ageing-associated matrix changes.
Importantly, the work supports a broader view of ageing biology. Muscle ageing is not only about loss of muscle mass or decline in contractile function. It also involves changes in the tissue microenvironment — including the matrix that surrounds cells, supports blood vessels and influences signalling between cells.
This has implications for how researchers study sarcopenia, the age-related decline in skeletal muscle mass and function. By defining more appropriate biological comparison points and mapping the transcriptomic matreotype of ageing muscle, the study provides a foundation for future work on how extracellular matrix remodelling contributes to tissue ageing.
The researchers also highlight the need to combine transcriptomic and proteomic approaches. Gene expression gives important insight into the biological programmes active during ageing, but proteins in the extracellular matrix can be difficult to study because they are often large, highly crosslinked and less soluble. Better integration of these methods could provide a fuller picture of how muscle tissue changes with age.
The study is fundamental in nature. It does not propose a treatment for ageing or sarcopenia. Instead, it helps clarify what should be compared, what biological processes are involved, and how the extracellular matrix may be understood as part of the ageing process.
Paper details
The paper, “Transcriptional profiling of male mouse muscle across aging stages: a gene ontology analysis of the muscle matreotype”, is published in BMC Genomics. DOI: 10.1186/s12864-026-12677-z.
Authors and affiliations
The study was carried out by A. Listrat, J. Tournayre and C. Boby from UMR Herbivores, INRAE, Université Clermont Auvergne and VetAgro Sup, France; C. Jousse and D. Béchet from the Human Nutrition Unit, INRAE and Université Clermont Auvergne, France; K. Lee from Daegu Gyeongbuk Institute of Science and Technology, Republic of Korea; H. Wang from Nanyang Technological University, Singapore; and K. L. Goh from Newcastle University in Singapore.
For further details, contact Dr Anne Listrat at [email protected], or Dr Kheng Lim Goh at [email protected].
