Reversal of a hallmark of brain ageing: Lipofuscin accumulation
Reversal of a hallmark of brain ageing: Lipofuscin accumulation
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DOI：
10.1016/j.neurobiolaging.2004.02.013
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Prior, AE
中科院分区：
文献类型：
--
作者：
Fonseca, DB;Sheehy, MRJ;Prior, AE
去除脂褐质细胞沉积物的前景引起了人们极大的兴趣，因为它们可能导致与年龄相关的功能衰退和疾病。在这里，我们使用十足目甲壳类动物模型来规避先前脂褐素损失研究中固有的许多问题。我们采用（a）经过验证的脂褐质定量方法，（b）体内环境，（c）基本自然的环境条件和（d）没有加速产生残留物质的情况或（e）应用药理学化合物。我们使用一种新颖的中枢神经系统活检技术，该技术既产生抗衰老作用，又允许对个体进行纵向采样，从而（f）避免可能遭受选择性死亡率偏差的传统纯横截面人口数据。我们定量证明，通过正常衰老产生的脂褐质可能会从神经组织中丢失。丢失的机制可能涉及胞吐作用和可能的血液运输。如果能够找到加速脂褐素去除的非破坏性方法，我们的结果表明，治疗逆转这种最普遍的细胞衰老表现是可能的。 (C) 2004 Elsevier Inc. 保留所有权利。
The prospect of removing cellular deposits of lipofuscin is of considerable interest because they may contribute to age related functional decline and disease. Here, we use a decapod crustacean model to circumvent a number of problems inherent in previous studies on lipofuscin loss. We employ (a) validated lipofuscin quantification methods, (b) an in vivo context, (c) essentially natural environmental conditions and (d) a situation without accelerated production of residual material or (e) application of pharmacological compounds. We use a novel CNS biopsy technique that produces both an anti-ageing effect and also permits longitudinal sampling of individuals, thus (f) avoiding conventional purely cross-sectional population data that may suffer from selective mortality biases. We quantitatively demonstrate that lipofuscin, accrued through normal ageing, can be lost from neural tissue. The mechanism of loss probably involves exocytosis and possibly blood transport. If non-disruptive ways to accelerate lipofuscin removal can be found, our results suggest that therapeutic reversal of this most universal manifestation of cellular ageing may be possible. (C) 2004 Elsevier Inc. All rights reserved.