Longevity and the Aging Extracellular Matrix

The extracellular matrix (ECM) is the network of proteins that exists between cells. It’s primary role is often viewed as one of structural support, yet the ECM is also important for cell-cell communication, as it transports and stores signalling molecules.

In ageing research, this facet of the ECM has been somewhat neglected in favour of studying intracellular mechanisms. Yet we know that degradation of the ECM occurs with age and contributes to disease. Indeed, young ECM even has the potential to rejuvenate senescent cells. There is a need to further understand the ensemble of proteins and ECM-cell interactions and how these alter with age. This understanding will hopefully lead to therapies that will restore the ageing ECM and thus avert age-related disease.

During aging, components of the ECM become damaged through fragmentation, glycation, crosslinking, and accumulation of protein aggregation, all of which contribute to age-related pathologies. Interestingly, placing senescent cells into a young ECM rejuvenates them and we found that many longevity-assurances pathways re-activate de-novosynthesis of ECM proteins during aging. This raises the question of what constitutes a young ECM to reverse aging or maintain health? In order to make inroads to answering this question, I suggest a systems-level approach of quantifying the matrisome or ECM compositions reflecting health, pathology, or phenotype and propose a novel term, the “matreotype”, to describe this. The matreotype is defined as the composition and modification of ECM or matrisome proteins associated with or caused by a phenotype, such as longevity, or a distinct and acute physiological state, as observed during aging or disease. Every cell type produces its unique ECM. Interestingly, cancer-cell types can even be identified based on their unique ECM composition. Thus, the matreotype reflects cellular identity and physiological status. Defined matreotypes could be used as biomarkers or prognostic factors for disease or health status during aging with potential relevance for personalized medicine. Treatment with biologics that alter ECM-to-cell mechanotransduction might be a strategy to reverse age-associated pathologies. An understanding of how to reverse from an old to a young matreotype might point towards novel strategies to rejuvenate cells and help maintain tissue homeostasis to promote health during aging.

Ewald, C. (2019). The Matrisome during Aging and Longevity: A Systems-Level Approach towards Defining Matreotypes Promoting Healthy Aging. doi: 10.20944/preprints201908.0063.v1