1 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and.
Am J Respir Crit Care Med. 2014 Apr 1;189(7):787-98. doi: 10.1164/rccm.201306-1043OC.
Aging is characterized by functional impairment and reduced capacity to respond appropriately to environmental stimuli and injury. With age, there is an increase in the incidence and severity of chronic and acute lung diseases. However, the relationship between age and the lung's reduced ability to repair is far from established and necessitates further research in the field.
Little is currently known about age-related phenomena in mesenchymal stem cells (MSCs). On account of their ability to protect the endothelium and the alveolar epithelium through multiple paracrine mechanisms, we looked for adverse effects that aging might cause in MSC biology. Such age-related changes might partly account for the increased susceptibility of the aging lung to injury.
We demonstrated that old mice have more inflammation in response to acute lung injury. To investigate the causes, we compared the global gene expression of aged and young bone marrow-derived MSCs (B-MSCs). Our results revealed that the expression levels of inflammatory response genes depended on the age of the B-MSCs. We demonstrated that the age-dependent decrease in expression of several cytokine and chemokine receptors is important for the migration and activation of B-MSCs. Finally, we showed by adoptive transfer of aged B-MSCs to young endotoxemic mice that aged cells lacked the antiinflammatory protective effect of their young counterparts.
Taken together, the decreased expression of cytokine and chemokine receptors in aged B-MSCs compromises their protective role by perturbing the potential of B-MSCs to become activated and mobilize to the site of injury.
衰老的特点是功能障碍以及对环境刺激和损伤的适当反应能力降低。随着年龄的增长，慢性和急性肺部疾病的发病率和严重程度增加。然而，年龄与肺部修复能力下降之间的关系远未确定，这需要在该领域进行进一步研究。
目前对于间充质干细胞（MSCs）的年龄相关现象知之甚少。鉴于它们通过多种旁分泌机制保护内皮细胞和肺泡上皮细胞的能力，我们寻找衰老可能对 MSC 生物学造成的不利影响。这种与年龄相关的变化可能部分解释了衰老肺部对损伤的易感性增加。
我们证明了老年小鼠对急性肺损伤的炎症反应更多。为了探究原因，我们比较了老年和年轻骨髓来源的 MSC（B-MSCs）的全基因组表达。结果表明，炎症反应基因的表达水平取决于 B-MSCs 的年龄。我们证明了几种细胞因子和趋化因子受体的年龄依赖性表达下降对于 B-MSCs 的迁移和激活很重要。最后，我们通过将老年 B-MSCs 过继转移到年轻内毒素血症小鼠中表明，老年细胞缺乏年轻细胞的抗炎保护作用。
综上所述，B-MSCs 中细胞因子和趋化因子受体的表达下调通过干扰 B-MSCs 激活和动员到损伤部位的潜力，损害了它们的保护作用。
