Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans
Apparent uncoupling of energy production and consumption in long-lived Clk mutants of Caenorhabditis elegans
复制标题
DOI：
10.1016/s0960-9822(99)80216-4
复制
发表时间：
1999-05-06
期刊：
影响因子：
9.2
通讯作者：
Vanfleteren, JR
中科院分区：
文献类型：
--
作者：
Braeckman, BP;Houthoofd, K;Vanfleteren, JR
秀丽隐杆线虫的 Clk 突变体的特点是时间过程整体减慢和寿命延长。据推测，Clk 突变会减慢许多细胞功能的速度并降低能量代谢率，可能导致活性氧产生减慢，进而导致衰老速度减慢 [1-3]。我们通过测量带有 Clk 基因 clk-1 和 gro-1 以及与 Clk 基因相互作用的其他三个基因的突变等位基因的各种菌株的呼吸速率、光生产能力 [4]（代谢潜力的衡量标准）和 ATP 水平来测试这一假设。我们发现，相对于野生型菌株，单个 Clk 突变体在其成年后的前 4-5 天中耗氧率略有降低，但代谢能力几乎没有变化。然而，这种差异随着年龄的增长而逐渐消失，并且老年 Clk 突变体最终保留了比野生型对照菌株 N2 更高的代谢能力。这些特征表明，相对于 Clk 突变体的时间顺序，生理时间被延迟。与N2菌株相比，衰老的clk-7和gro-1突变体还保留了显着升高的ATP水平，并且daf-2或age-1（影响寿命的基因）突变的同时存在增强了这种效应。因此，在这些突变体中，能量的产生和消耗似乎是不相关的。转录因子 daf-16 的突变抑制了 Age 和 ATP 表型，但不会抑制 clk-1 突变导致的呼吸速率降低。
Clk mutants of Caenorhabditis elegans are characterised by an overall slow down of temporal processes and increase in life span. It was hypothesised that Clk mutations slow down the pace of many cellular functions and lower the rate of energy metabolism, possibly resulting in slower production of reactive oxygen species which in turn could result in slower ageing [1-3]. We tested this hypothesis by measuring respiration rates, light production capacities [4] (a measure of metabolic potential) and ATP levels in various strains harbouring mutant alleles of the Clk genes clk-1 and gro-1 and of three other genes that interact with the Clk genes. We found a mild reduction of oxygen consumption rates but little alteration of metabolic capacities in the single Clk mutants during the first 4-5 days of their adult lives, relative to the wild-type strain. This difference tended to fade away with increasing age, however, and aged Clk mutants eventually retained higher metabolic capacities than the wild-type control strain N2. These profiles are suggestive of physiological time being retarded, relative to chronological time in Clk mutants. Ageing clk-7 and gro-1 mutants also retained substantially elevated ATP levels relative to the N2 strain, and the simultaneous presence of mutations in daf-2 or age-1 - genes that affect longevity - boosted this effect. Thus, energy production and consumption appear to be uncoupled in these mutants. Mutation in the transcription factor daf-16 suppressed the Age and ATP phenotypes, but not the reduction of respiration rate imparted by mutation in clk-1.