New insights into how senescent cells play a role in wound healing not only through its secretory action but also by impacting on cell mechanics have been provided by a study performed at Charité Universitätsmedizin Berlin and published in Aging Cell. Led by Uwe Kornak, professor at the Institute of Human Genetics Göttingen, and Ansgar Petersen, professor at Julius Wolff Institute of Charité, a team of scientists has revealed that cellular senescence beneficially influences tissue formation by modulating cell mechanics and extracellular matrix (ECM) synthesis and composition.

Senescence is a multistep process in which cells, in response to different stresses and damage, go from a transient cell cycle inhibition to an irreversible state in which they no longer divide. Senescent cells do not die but remain metabolically active, secreting a characteristic combination of proteins and factors that can affect the cell’s surrounding environment, the extracellular matrix, and neighboring cells. Accumulation of senescent cells is a hallmark of ageing and a factor in the development of ageing-associated pathologies. These detrimental effects are also investigated intensively at the Institute of Human Genetics. There is, however, also a positive aspect of cellular senescence: Short-term presence of senescent cells promotes wound healing and contributes to scar development. However, it has so far not been known that senescence has also a direct role in tissue formation beyond its paracrine signaling.

The researchers used a specific in vitro wound healing model of primary human skin fibroblasts in which they induced cellular senescence by two different mechanisms (either by DNA damage or by overexpression of cell cycle inhibitors). They investigated the effects of both types of senescence on cell migration, morphology and adhesion. Their investigations showed that cellular senescence modulated size and composition of focal adhesions. These multiprotein structures anchor cells to the extracellular matrix and are responsible for transferring cellular forces. In all senescent cells, increased single cell forces were observed. However, in DNA damage-mediated senescence, contrary to senescence induced by cell cycle inhibitors, degenerative changes in ECM acted against contraction in 3D cell cultures. Thus, depending on the type, senescence showed different and partly conversing effects on tissue formation, contraction and tensioning. In addition to mechanical effects, the study also revealed altered expression profiles for genes encoding ECM-related proteins including collagens, lysyl oxidases and matrix metalloproteinases.

Contact: Prof. Dr. med. Uwe Kornak, uwe.kornak@med.uni-goettingen.de