The mechanobiology of ageing: reproduction of the ageing and rejuvenating ECM environment

衰老是一个慢性过程，代表着人体的永久性和渐进性退化。它可以是生理的，也可以是病理的，后者与癌症、糖尿病、阿尔茨海默氏症和心血管疾病等疾病有关。与衰老有关的病理或生理细胞衰退包括细胞和细胞外基质(ECM)的机械性能的恶化，以及机械敏感和机械传导信号的改变。机械转导是细胞感知外部机械刺激并将其转化为生化信号的能力，这一现象是许多细胞活动的基础。事实上，机械力是调节基因表达、黏附、迁移和细胞命运的关键因素，这些都是组织内稳的重要因素。因此，理解多面和短暂的衰老过程如何影响这些力的传递途径是必要的，以加强对与衰老相关的调节失调和疾病的理解。该项目旨在研究细胞外基质粘弹性特性对细胞衰老的影响，了解细胞在生理和病理老化过程中是如何受到影响的，并逆转这一过程，诱导细胞恢复活力。这项工作有两个主要目标：找出诊断衰老相关疾病的有用生物标志物，并定义一种可能的再生过程，作为预防或治疗与衰老相关的病理性失调的治疗方案。

Ageing is a chronic process that represents a permanent and gradual deterioration of the human body. It can be either physiological or pathological, the latter being related to diseases such as cancers, diabetes, Alzheimer's and cardiovascular disease.The pathological or physiological cellular decay associated with ageing includes thedeterioration of mechanical properties of the cell and the extracellular matrix (ECM), and alterations of mechanosensitive and mechanotransductive signalling.Mechanotransduction is the ability of a cell to perceive external mechanical stimuli and translate them into biochemical signals, a phenomenon that is the basis for many cellular activities. Indeed, mechanical forces are pivotal to regulate gene expression, adhesion, migration and cell fate, which are all important factors for tissue homeostasis.Understanding how the multifaced and temporal ageing process affects the pathways involved in the transmission of these forces is, therefore, necessary to enhance the comprehension of ageing-related dysregulation and diseases. The project aims to study the impact of the ECM viscoelastic properties on cellular senescence, either to understand how cells are affected during physiological and pathological ageing and to invert this process inducing the rejuvenation of the cells.This work has two major objectives: identify useful biomarkers for the diagnosis of ageing related diseases and define a possible rejuvenation process as a therapeutical solution to prevent or treat pathological ageing-associated dysregulations.