Decline of lymphatic vessel density and function in murine skin during aging

Decline of lymphatic vessel density and function in murine skin during aging
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DOI:
10.1007/s10456-015-9479-0
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发表时间:
2015-10-01
期刊:
影响因子:
9.8
通讯作者:
Proulx, Steven T.
Proulx, Steven T.
中科院分区:
医学1区
文献类型:
--
作者:
Karaman, Sinem;Buschle, Dorina;Proulx, Steven T.

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淋巴管在许多老年人患病率增加的疾病的发病机制中发挥着重要作用。然而,衰老过程对淋巴系统的影响仍然相对未知。我们应用非侵入性成像和整体染色技术来评估三个不同年龄组小鼠的淋巴管功能和形态:2个月(年轻)、7个月(中年)和18个月(老年)。我们首先开发并验证了一种新方法,使用淋巴特异性近红外示踪剂来量化小鼠耳部皮肤的淋巴清除率。使用这种方法,我们发现衰老过程中淋巴管功能显着下降,因为老年小鼠的淋巴清除显着延迟。与年轻对照组相比,老年小鼠皮肤的这种功能丧失与淋巴管密度降低和淋巴网络复杂性降低相关。老年小鼠皮肤的血管渗漏略有增加,表明淋巴功能下降并非由老年皮肤毛细血管过滤减少引起。随着年龄的增长,淋巴管功能下降可能对许多与衰老相关的疾病的发病机制有影响。
Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.