Objective
The increasing elderly population poses a dual challenge to the viability of both global health and our current welfare systems. One of the pivotal aspects of aging involves the accumulation of damaged cells, known as senescent cells, in organs. While these cells play a role in coordinating tissue repair whenever damage occurs, their aberrant accumulation disturbs normal tissue function, resulting in an unbearable burden that ultimately leads to aging. Understanding how these cells accumulate within the organism, a yet unresolved question, would offer invaluable insights into the aging process. We have recently reported that damaged cells rely on Integrins, a family of membrane proteins, to implement senescence over cell death, leading to their accumulation within injured tissues. Remarkably, Integrins are known as the major cellular receptors binding to the surrounding extracellular matrix (ECM). Considering these precedents, we aim to take a step further and investigate whether the composition and status of the ECM can influence the buildup of senescent cells by impacting the choice between senescence and cell death upon injury, a possibility not explored before. Here, we aim to assess whether certain ECM proteins might act as pro-senescence factors by desensitizing damaged cells to death, favoring survival and aberrant senescence instead. We will thoroughly characterize multiple cell culture and mouse models of senescence implementation following damage, aiming to unveil the mechanisms controlling this phenomenon. Leveraging these findings, we will modulate the occurrence of cell senescence through ECM reengineering in mice, seeking to establish a revolutionary approach to address aging and tissue fibrosis. In sum, by uncovering unsuspected links between the ECM status and cell senescence implementation, ChECMate senescence would signify a paradigm change that would enable an unprecedented strategy in targeting cellular senescence in detrimental scenarios.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
28006 Madrid
Spain