Cellular Senescence and Lung Function during Aging Yin and Yang
Cellular Senescence and Lung Function during Aging Yin and Yang
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DOI：
10.1513/annalsats.201609-703aw
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发表时间：
2016-12-01
影响因子：
8.3
通讯作者：
Campisi, Judith
中科院分区：
文献类型：
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作者：
Campisi, Judith
细胞衰老是一种细胞命运决定和应激反应，它需要细胞增殖的永久停止，并伴有复杂的分泌表型。在大多数（如果不是全部的话）哺乳动物组织中，衰老细胞的数量会随着年龄的增长而增加，包括呼吸道和肺部。在慢性阻塞性肺疾病和肺气肿等与年龄相关的疾病中，与年龄匹配的对照组相比，它们的增加数量也高于预期。衰老反应是一把双刃剑。增殖阻滞通过防止有肿瘤转化风险的应激或受损细胞的繁殖来抑制癌症的发展。然而，这种阻滞也会抑制干细胞或祖细胞的增殖，从而阻碍组织修复和再生。同样，分泌型可以通过短暂地提供组织修复所需的生长因子和初始炎症刺激来促进伤口愈合。然而，当长期存在时，衰老细胞的分泌表型可以驱动病理性炎症，这有助于许多与年龄相关的病理，包括癌症。现在有转基因和小分子原型可以清除衰老细胞，至少在小鼠模型中，从而提高健康寿命和平均寿命。下一个挑战将是开发干预和补充措施，既能消除衰老细胞的有害影响，又能保持它们的有益作用。
Cellular senescence is a cell fate decision and stress response that entails a permanent arrest of cell proliferation coupled to a complex secretory phenotype. Senescent cells increase in number with age in most, if not all, mammalian tissues, including the airways and lungs. They also increase at greater than expected numbers, compared with age-matched controls, at sites of age-related pathologies such as chronic obstructive pulmonary disorder and emphysema. The senescence response is a double-edged sword. The proliferative arrest suppresses the development of cancer by preventing the propagation of stressed or damaged cells that are at risk for neoplastic transformation. However, this arrest can also curtail the proliferation of stem or progenitor cells and thus hamper tissue repair and regeneration. Similarly, the secretory phenotype can promote wound healing by transiently providing growth factors and the initial inflammatory stimulus that is required for tissue repair. However, when chronically present, the secretory phenotype of senescent cells can drive pathological inflammation, which contributes to a host of age-related pathologies, including cancer. There are now transgenes and prototype small molecules that can clear senescent cells, at least in mouse models, and thus improve health span and median life span. The next challenge will be to develop interventions and supplements that can abrogate the deleterious effects of senescent cells while preserving their beneficial effects.