Senescence is a biological process that induces a permanent cell cycle arrest and a specific gene expression program in response to various stressors. Following studies over the last few decades, the concept of senescence has evolved from an antiproliferative mechanism in cancer (oncogene-induced senescence) to a critical component of physiological processes associated with embryonic development, tissue regeneration, ageing and its associated diseases. In somatic cells, oncogenic mutations in RAS-MAPK pathway genes are associated with oncogene-induced senescence and cancer, while germline mutations in the same pathway are linked to a group of monogenic developmental disorders generally termed RASopathies. Here, we consider that in these disorders, senescence induction may result in opposing outcomes, a tumour protective effect and a possible contributor to a premature ageing phenotype identified in Costello syndrome, which belongs to the RASopathy group. In this review, we will highlight the role of senescence in organismal homeostasis and we will describe the current knowledge about senescence in RASopathies. Additionally, we provide a perspective on examples of experimentally characterised RASopathy mutations that, alone or in combination with various stressors, may also trigger an age-dependent chronic senescence, possibly contributing to the age-dependent worsening of RASopathy pathophenotype and the reduction of lifespan.

衰老是一种生物学过程，可诱导永久性细胞周期停滞和响应各种压力源的特定基因表达程序。经过过去几十年的研究，衰老的概念已经从癌症中的抗增殖机制（癌基因诱导的衰老）演变为与胚胎发育、组织再生、衰老及其相关疾病相关的生理过程的关键组成部分。在体细胞中，RAS-MAPK 通路基因的致癌突变与致癌基因诱导的衰老和癌症有关，而同一通路中的种系突变与一组通常称为 RASopathies 的单基因发育障碍有关。在这里，我们认为在这些疾病中，衰老诱导可能会导致相反的结果，肿瘤保护作用和可能导致在属于 RAS 病组的 Costello 综合征中发现的过早衰老表型。在这篇综述中，我们将强调衰老在机体稳态中的作用，我们将描述目前关于 RASopathies 衰老的知识。此外，我们提供了对实验表征的 RASpath 突变示例的看法，这些突变单独或与各种压力因素结合，也可能引发年龄依赖性慢性衰老，可能导致 RASpath 病理表型的年龄依赖性恶化和寿命缩短。我们将强调衰老在机体稳态中的作用，我们将描述目前关于 RASopathies 衰老的知识。此外，我们提供了对实验表征的 RASpath 突变示例的看法，这些突变单独或与各种压力因素结合，也可能引发年龄依赖性慢性衰老，可能导致 RASpath 病理表型的年龄依赖性恶化和寿命缩短。我们将强调衰老在机体稳态中的作用，我们将描述目前关于 RASopathies 衰老的知识。此外，我们提供了对实验表征的 RASpath 突变示例的看法，这些突变单独或与各种压力因素结合，也可能引发年龄依赖性慢性衰老，可能导致 RASpath 病理表型的年龄依赖性恶化和寿命缩短。