Cellular senescence is implicated in a wide range of physiological and pathological conditions throughout an organism's entire lifetime. In particular, it has become evident that senescence plays a causative role in aging and age-associated disorders. This is not due simply to the loss of function of senescent cells. Instead, the substantial alterations of the cellular activities of senescent cells, especially the array of secretory factors, impact the surrounding tissues or even entire organisms. Such non-cell-autonomous functionality is largely coordinated by tissue-specific genes, constituting a cell fate–determining state. Senescence can be viewed as a gain-of-function phenotype or a process of cell identity shift. Cellular functionality or lineage-specific gene expression is tightly linked to the cell type–specific epigenetic landscape, reinforcing the heterogeneity of senescence across cell types. Here, we aim to define the senescence cellular functionality and epigenetic features that may contribute to the gain-of-function phenotype.

中文翻译：

---

衰老：源自细胞核深处的身份危机

细胞衰老与生物体整个生命周期的各种生理和病理条件有关。特别是，很明显衰老在衰老和与年龄相关的疾病中起着致病作用。这不仅仅是由于衰老细胞功能丧失造成的。相反，衰老细胞的细胞活性的实质性改变，尤其是一系列分泌因子，会影响周围组织甚至整个生物体。这种非细胞自主功能很大程度上是由组织特异性基因协调的，构成了细胞命运决定状态。衰老可以被视为功能获得表型或细胞身份转变的过程。细胞功能或谱系特异性基因表达与细胞类型特异性表观遗传景观紧密相关，增强了不同细胞类型衰老的异质性。在这里，我们的目标是定义可能有助于功能获得表型的衰老细胞功能和表观遗传特征。