PDF(Pubmed)
Abstract：
Cellular senescence is implicated in ageing and associated with a broad spectrum of age-related diseases. Importantly, a cell can initiate the senescence program irrespective of the organism\'s age. Various stress signals, including those defined as ageing hallmarks and alterations leading to cancer development, oncogene activation, or loss of cancer-suppressive functions, can trigger cellular senescence. The primary outcome of these alterations is the activation of nuclear factor (NF)-κB, thereby inducing the senescence-associated secretory phenotype (SASP). Proinflammatory cytokines and chemokines, components of this phenotype, contribute to chronic systemic sterile inflammation, commonly referred to as inflamm-ageing. This inflammation is linked to age-related diseases (ARDs), frailty, and increased mortality in older individuals. Additionally, senescent cells (SCs) accumulate in multiple tissues with age and are believed to underlie the organism functional decline, as demonstrated by models. An escalating effort has been dedicated to identify senotherapeutics that selectively target SCs by inducing apoptosis; these drugs are termed senolytics. Concurrently, small molecules that suppress senescent phenotypes without causing cell death are known as senomorphics. Both natural and synthetic senotherapeutics, along with immunotherapies employing immune cell-mediated clearance of SCs, currently represent the most promising strategies to combat ageing and ARDs. Indeed, it is fascinating to observe that information regarding the immune reaction to SCs indicates that regulation by specific lymphocyte subsets, elevated in the oldest centenarians, plays a role in attaining extreme longevity. Regardless, the application of methods already utilized in cancer treatment, such as CAR cells and monoclonal antibodies, broadens the spectrum of potential approaches to be utilized.
摘要：
细胞衰老与衰老有关，并与广泛的年龄相关疾病有关。重要的是,细胞可以启动衰老程序，而与生物体的年龄无关。各种应力信号，包括那些被定义为衰老标志和导致癌症发展的改变，癌基因激活，或者癌症抑制功能的丧失，可以触发细胞衰老。这些改变的主要结果是核因子（NF）-κB的激活，从而诱导衰老相关分泌表型(SASP)。促炎细胞因子和趋化因子，这种表型的组成部分，导致慢性全身性无菌性炎症，通常被称为炎症老化。这种炎症与年龄相关疾病（ARD）有关，脆弱,和增加老年人的死亡率。此外,衰老细胞（SCs）随着年龄的增长在多个组织中积累，被认为是生物体功能下降的基础，正如模型所证明的那样。不断升级的努力致力于鉴定通过诱导细胞凋亡选择性靶向SCs的感官治疗剂;这些药物被称为senoletics。同时,抑制衰老表型而不引起细胞死亡的小分子被称为衰老形态学。天然和合成的感官疗法，以及采用免疫细胞介导的SC清除的免疫疗法，目前是对抗衰老和ARD的最有前途的战略。的确,令人着迷的是，观察到关于对SC的免疫反应的信息表明特定淋巴细胞亚群的调节，在最古老的百岁老人中，在实现极端长寿方面发挥作用。无论如何,已经在癌症治疗中使用的方法的应用，如CAR细胞和单克隆抗体，拓宽了要利用的潜在方法的范围。
