Organ reserve, excess metabolic capacity, and aging
Organ reserve, excess metabolic capacity, and aging
复制标题
DOI：
10.1007/s10522-018-9746-8
复制
发表时间：
2018-04-01
期刊：
影响因子：
4.5
通讯作者：
Dhahbi, Joseph M.
中科院分区：
文献类型：
--
作者：
Atamna, Hani;Tenore, Alfred;Dhahbi, Joseph M.
“器官储备”指的是器官在反复应激后能够成功地恢复到原来的生理状态的能力。临床证据表明，器官储备与老年人应对额外工作量或压力的能力相关，这表明在衰老过程中发挥了作用。虽然器官储备在临床上得到了很好的证明，但在分子水平上还没有明确的定义。有趣的是，一些代谢途径表现出过剩的代谢能力(例如，生物能量途径、抗氧化剂系统、可塑性)。这些途径包括数量和/或活性超过体内基本生理需求所需的分子成分(例如，线粒体复合体IV或糖酵解酶)。我们认为，线粒体DNA拷贝数的过剩和端粒的串联DNA重复是可能构成过剩能力的内在嵌入结构组件的额外例子。这些过剩的能力可能会赋予中间新陈代谢立即应对或管理增加的工作量或压力的能力。因此，过量的代谢能力可以被视为一种与生俱来的适应机制，它充实了器官储备，并有助于细胞防御系统。如果代谢过剩的能力或器官储备受损或耗尽，细胞应对压力的能力就会降低。在这种情况下，细胞会衰老、转化或死亡。在这篇综述中，我们讨论了作为与器官储备和细胞老化有关的综合代谢途径的过剩代谢能力和结构能力。
"Organ reserve" refers to the ability of an organ to successfully return to its original physiological state following repeated episodes of stress. Clinical evidence shows that organ reserve correlates with the ability of older adults to cope with an added workload or stress, suggesting a role in the process of aging. Although organ reserve is well documented clinically, it is not clearly defined at the molecular level. Interestingly, several metabolic pathways exhibit excess metabolic capacities (e.g., bioenergetics pathway, antioxidants system, plasticity). These pathways comprise molecular components that have an excess of quantity and/or activity than that required for basic physiological demand in vivo (e.g., mitochondrial complex IV or glycolytic enzymes). We propose that the excess in mtDNA copy number and tandem DNA repeats of telomeres are additional examples of intrinsically embedded structural components that could comprise excess capacity. These excess capacities may grant intermediary metabolism the ability to instantly cope with, or manage, added workload or stress. Therefore, excess metabolic capacities could be viewed as an innate mechanism of adaptability that substantiates organ reserve and contributes to the cellular defense systems. If metabolic excess capacities or organ reserves are impaired or exhausted, the ability of the cell to cope with stress is reduced. Under these circumstances cell senescence, transformation, or death occurs. In this review, we discuss excess metabolic and structural capacities as integrated metabolic pathways in relation to organ reserve and cellular aging.