Arum Oge, Dawson John Alexander, Smith Daniel Larry, Kopchick John J, Allison David B, Bartke Andrzej
Department of Internal Medicine, Southern Illinois University-School of Medicine, Springfield, IL, 62794, USA.
Aging Cell. 2015 Jun;14(3):483-90. doi: 10.1111/acel.12318. Epub 2015 Feb 26.
That one or multiple measures of metabolic rate may be robustly associated with, or possibly even causative of, the progression of aging-resultant phenotypes such as lifespan is a long-standing, well-known mechanistic hypothesis. To broach this hypothesis, we assessed metabolic function and spontaneous locomotion in two genetic and one dietary mouse models for retarded aging, and subjected the data to mediation analyses to determine whether any metabolic or locomotor trait could be identified as a mediator of the effect of any of the interventions on senescence. We do not test the hypothesis of causality (which would require some experiments), but instead test whether the correlation structure of certain variables is consistent with one possible pathway model in which a proposed mediating variable has a causal role. Results for metabolic measures, including oxygen consumption and respiratory quotient, failed to support this hypothesis; similar negative results were obtained for three behavioral motion metrics. Therefore, our mediation analyses did not find support that any of these correlates of decelerated senescence was a substantial mediator of the effect of either of these genetic alterations (with or without caloric restriction) on longevity. Further studies are needed to relate the examined phenotypic characteristics to mechanisms of aging and control of longevity.
代谢率的一项或多项指标可能与衰老相关表型（如寿命）的进展密切相关，甚至可能是其成因，这是一个长期存在且广为人知的机制假说。为探讨这一假说，我们在两种基因模型和一种饮食模型的延缓衰老小鼠中评估了代谢功能和自发运动能力，并对数据进行中介分析，以确定是否能将任何代谢或运动特征识别为这些干预措施对衰老影响的中介因素。我们并未检验因果关系假说（这需要一些实验），而是检验某些变量的相关结构是否与一种可能的通路模型一致，在该模型中，一个假定的中介变量具有因果作用。包括耗氧量和呼吸商在内的代谢指标结果未能支持这一假说；三个行为运动指标也得到了类似的负面结果。因此，我们的中介分析并未发现这些与衰老减缓相关的因素中有任何一个是这些基因改变（有或没有热量限制）对寿命影响的实质性中介因素。需要进一步研究将所研究的表型特征与衰老机制和寿命控制联系起来。
