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衰老、 hormesis 和毒性的 Gompertz 年龄特异性死亡率模型:固定剂量研究。

A Gompertz age-specific mortality rate model of aging, hormesis, and toxicity: fixed-dose studies.

作者信息

Neafsey P J, Boxenbaum H, Ciraulo D A, Fournier D J

机构信息

Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts 02111.

出版信息

Drug Metab Rev. 1988;19(3-4):369-401. doi: 10.3109/03602538808994141.

Abstract

Based on the proposition that the logarithm of age-specific mortality rate (Gompertzian) is a linear measure of the mean intensity of injury for a homogeneous mammalian population in a uniform environment, a model was developed which characterizes mortality experience resulting from both toxic and hormetic actions. The mortality-reducing component (longevity hormesis) was assumed to be reversible; toxic effects, on the other hand, were assumed to accumulate irreversibly. Following chronic low-dose administration of selected toxic substances, it was demonstrated (in certain cases) that longevity hormesis could enhance lifespan, even in the presence of concomitant toxicity. Even when toxicity was evident, hormesis could ameliorate some of the mortality. The assumption that high-dose chronic toxicity studies can generate realistic estimates of risk at low doses is challenged.

摘要

基于这样一个命题

特定年龄死亡率的对数(冈珀茨曲线)是均匀环境中同质哺乳动物群体平均损伤强度的线性度量,开发了一个模型来描述由毒性作用和 hormetic 作用导致的死亡经历。降低死亡率的成分(长寿 hormesis)被假定为可逆的;另一方面,毒性作用被假定为不可逆地积累。在长期低剂量施用选定的有毒物质后,(在某些情况下)证明即使存在伴随的毒性,长寿 hormesis 也可以延长寿命。即使毒性明显,hormesis 也可以减轻一些死亡率。高剂量慢性毒性研究能够对低剂量风险做出实际估计的假设受到了挑战。

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