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首页> 外文期刊>Experimental Gerontology >Hepatic disposal of advanced glycation end products during maturation and aging
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Hepatic disposal of advanced glycation end products during maturation and aging

机译：成熟和老化过程中高级糖化终产物的肝处置

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摘要

Aging is characterized by progressive loss of metabolic and biochemical functions and accumulation of metabolic by-products, including advanced glycation end products (AGEs), which are observed in several pathological conditions. A number of waste macromolecules, including AGEs are taken up from the circulation by endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs). However, AGEs still accumulate in different tissues with aging, despite the presence of this clearance mechanism. The aim of the present study was to determine whether the efficiency of LSECs and KCs for disposal of AGEs changes through aging. Results: After intravenous administration of 14C-AGE-albumin in pre-pubertal, young adult, middle aged and old mice, more than 90% of total recovered 14C-AGE was liver associated, irrespective of age. LSECs and KCs represented the main site of uptake. A fraction of the 14C-AGE degradation products (14C-AGE-DPs) was stored for months in the lysosomes of these cells after uptake. The overall rate of elimination of 14C-AGE-DPs from the liver was markedly faster in pre-pubertal than in all post-pubertal age groups. The ability to eliminate 14C-AGE-DPs decreased to similar extents after puberty in LSECs and KCs. A rapid early removal phase was characteristic for all age groups except the old group, where this phase was absent. Conclusions: Removal of AGE-DPs from the liver scavenger cells is a very slow process that changes with age. The ability of these cells to dispose of AGEs declines after puberty. Decreased AGE removal efficiency early in life may lead to AGE accumulation.
机译：衰老的特征是代谢和生化功能的逐步丧失以及代谢副产物（包括晚期糖基化终产物（AGEs））的积累，这在几种病理情况下都可以观察到。包括AGEs在内的许多废物大分子通过内吞作用从循环系统吸收，主要进入肝窦状内皮细胞（LSEC）和库普弗细胞（KCs）。但是，尽管存在这种清除机制，但随着年龄的增长，AGEs仍会累积在不同的组织中。本研究的目的是确定LSEC和KC处理AGEs的效率是否会随着年龄的增长而改变。结果：在青春期前，成年，中年和老年小鼠中静脉内施用14C-AGE-白蛋白后，不论年龄大小，回收的14C-AGE总量中有90％以上与肝脏相关。 LSEC和KC是吸收的主要场所。摄取后，一部分14C-AGE降解产物（14C-AGE-DPs）在这些细胞的溶酶体中保存了数月。青春期前，从肝脏中清除14C-AGE-DPs的总体速度明显快于所有青春期后组。在LSEC和KC中，青春期后消除14C-AGE-DP的能力下降了相似的程度。除老年组外，所有年龄组均具有快速的早期去除阶段。结论：从肝脏清除剂细胞中去除AGE-DPs是一个非常缓慢的过程，随着年龄的增长而变化。这些细胞处理AGEs的能力在青春期后下降。在生命早期降低AGE去除效率可能会导致AGE积累。

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