Although senescence was originally described as an in vitro acquired cellular characteristic, it was recently recognized that senescence is physiologically and pathologically involved in aging and age-related diseases in vivo. The definition of cellular senescence has expanded to include the growth arrest caused by various cellular stresses, including DNA damage, inadequate mitochondria function, activated oncogene or tumor suppressor genes and oxidative stress. While senescence in normal aging involves various tissues over time and contributes to a decline in tissue function even with healthy aging, disease-induced premature senescence may be restricted to one or a few organs triggering a prolonged and more intense rate of accumulation of senescent cells than in normal aging. Organ-specific high senescence rate could lead to chronic diseases, especially in post-mitotic rich tissue. Recently, two opposite acquired pathological conditions related to skin pigmentation were described to be associated with premature senescence: vitiligo and melasma. In both cases, it was demonstrated that pathological dysfunctions are not restricted to melanocytes, the cell type responsible for melanin production and transport to surrounding keratinocytes. Similar to physiological melanogenesis, dermal and epidermal cells contribute directly and indirectly to deregulate skin pigmentation as a result of complex intercellular communication. Thus, despite senescence usually being reported as a uniform phenotype sharing the expression of characteristic markers, skin senescence involving mainly the dermal compartment and its paracrine function could be associated with the disappearance of melanocytes in vitiligo lesions and with the exacerbated activity of melanocytes in the hyperpigmentation spots of melasma. This suggests that the difference may arise in melanocyte intrinsic differences and/or in highly defined microenvironment peculiarities poorly explored at the current state of the art. A similar dualistic phenotype has been attributed to intratumoral stromal cells as cancer-associated fibroblasts presenting a senescent-like phenotype which influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. Here, we present a framework dissecting senescent-related molecular alterations shared by vitiligo and melasma patients and we also discuss disease-specific differences representing new challenges for treatment.

尽管衰老最初被描述为体外获得的细胞特征，但最近认识到衰老在体内与衰老和与年龄相关的疾病有关，在生理和病理上都涉及。细胞衰老的定义已扩展到包括由各种细胞应激引起的生长停滞，这些细胞应激包括DNA损伤，线粒体功能不足，激活的癌基因或肿瘤抑制基因以及氧化应激。尽管正常衰老过程中的衰老会随着时间的推移而累及各种组织，甚至在健康衰老的情况下也会导致组织功能的下降，但疾病引起的过早衰老可能仅限于一个或几个器官，从而导致衰老细胞的累积和积累速率比长期衰老的细胞更为强烈。在正常的衰老中。器官特异的高衰老率可能导致慢性疾病，特别是在有丝分裂后丰富的组织中。最近，描述了与皮肤色素沉着相关的两种相反的获得性病理状况：白癜风和黄褐斑。在这两种情况下 已经证实，病理功能障碍不限于黑素细胞，黑素细胞是负责黑色素产生并转运至周围角质形成细胞的细胞类型。类似于生理性黑色素生成，由于复杂的细胞间通讯，真皮和表皮细胞直接或间接地有助于解除皮肤色素沉着。因此，尽管通常将衰老报告为共享特征标记表达的统一表型，但主要涉及真皮区室及其旁分泌功能的皮肤衰老可能与白癜风病变中黑素细胞的消失以及色素沉着中黑素细胞活性的加剧有关。黄褐斑。这表明该差异可能出现在黑素细胞固有差异和/或在当前技术水平下未充分探索的高度定义的微环境特性中。与肿瘤相关的成纤维细胞呈类似衰老样表型的肿瘤相关基质细胞，也被归因于肿瘤内基质细胞，它以促进肿瘤或抑制肿瘤的方式影响肿瘤细胞的行为。在这里，我们提出了解剖白癜风和黄褐斑患者共有的与衰老相关的分子变化的框架，并且我们还讨论了代表治疗新挑战的疾病特异性差异。与肿瘤相关的成纤维细胞呈类似衰老样表型的肿瘤相关基质细胞，也被归因于肿瘤内基质细胞，它以促进肿瘤或抑制肿瘤的方式影响肿瘤细胞的行为。在这里，我们提出了解剖白癜风和黄褐斑患者共有的与衰老相关的分子变化的框架，并且我们还讨论了代表治疗新挑战的疾病特异性差异。与肿瘤相关的成纤维细胞呈类似衰老样表型的肿瘤相关基质细胞，也被归因于肿瘤内基质细胞，它以促进肿瘤或抑制肿瘤的方式影响肿瘤细胞的行为。在这里，我们提出了解剖白癜风和黄褐斑患者共有的与衰老相关的分子变化的框架，并且我们还讨论了代表治疗新挑战的疾病特异性差异。