Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.
Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.
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DOI：
10.3390/biology7010001
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发表时间：
2017-12-23
期刊：
影响因子：
4.2
通讯作者：
Fontana W
中科院分区：
文献类型：
--
作者：
Apfeld J;Fontana W
人们通常认为，但尚未确定的是，主要的神经退行性疾病，如帕金森病，不仅与年龄有关（其发病率随时间而变化），而且实际上与衰老有关（其发病率与决定寿命的过程有关）。为了确定对衰老过程的依赖性，需要疾病发作和寿命的联合概率分布。对于人类帕金森病，这种联合分布是不可用的，因为这种疾病缩短了寿命。为了获得一个联合分布，我们求助于一个既定的C。elegans帕金森病模型，其中多巴胺能神经元的损失不是致命的。我们发现寿命与单个神经元的损失无关。因此，神经元损失是年龄依赖性和年龄无关性的。我们还发现，对胰岛素/IGF 1信号传导的延长寿命的干预加速了特定多巴胺能神经元的损失，同时使死亡和神经元损失时间不相关。这表明，相同的遗传编码的胰岛素/IGF 1信号传导机制的不同和分隔的实例独立地控制C中的神经变性和寿命。优美的虽然人类的情况可能会有所不同，但我们的研究呼吁注意需要严格区分年龄依赖和衰老依赖。
It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson’s disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson’s disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson’s disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans. Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.
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影响因子：
64.8
作者：
Herndon, LA;Schmeissner, PJ;Driscoll, M
通讯作者：
Driscoll, M
DOI：
10.1093/gerona/50a.5.b254
发表时间：
1995-09-01
影响因子：
5.1
作者：
DUHON, SA;JOHNSON, TE
通讯作者：
JOHNSON, TE
DOI：
10.1073/pnas.0711018105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Hamamichi, Shusei;Rivas, Renee N.;Caldwell, Guy A.
通讯作者：
Caldwell, Guy A.
DOI：
10.18632/aging.100034
发表时间：
2009-03-28
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
7.8
作者：
Gerstbrein, B;Stamatas, G;Driscoll, M
通讯作者：
Driscoll, M