GIGA-CRC In Vivo Imaging, Université de Liège, Liège, Belgique.
Psychology and Neuroscience of Cognition Research Unit, Université de Liège, Liège, Belgique.
PLoS One. 2024 May 13;19(5):e0303343. doi: 10.1371/journal.pone.0303343. eCollection 2024.
Genetic variability in the dopaminergic system could contribute to age-related impairments in executive control. In this study, we examined whether genetic polymorphism for catechol-O-methyltransferase (COMT Val158Met) is related to performance on updating, shifting and inhibition tasks.
We administered a battery of executive tasks assessing updating, shifting and inhibition functions to 45 older and 55 younger healthy participants, and created composite z-scores associated to each function. Six groups were created based on genetic alleles (Val/Val, Val/Met, Met/Met) derived from the COMT gene and age (younger, older). Age and genotype effects were assessed with t-test and ANOVA (p<0.05).
A lower performance was observed in the older group for the three executive processes, and more particularly for inhibition. Moreover, older participants homozygous for the Val allele have a lower performance on the inhibition composite in comparison to younger Val/Val.
These results confirm presence of executive performance decrease in healthy aging. With regard to genetic effect, older participants seem particularly disadvantaged when they have a lower baseline dopamine level (i.e., Val/Val homozygous) that is magnified by aging, and when the executive measure emphasize the need of stable representations (as in inhibition task requiring to maintain active the instruction to not perform an automated process).
多巴胺能系统的遗传变异性可能导致与年龄相关的执行控制损伤。在这项研究中,我们研究了儿茶酚-O-甲基转移酶(COMT Val158Met)的遗传多态性是否与更新、转换和抑制任务的表现相关。
我们对 45 名老年和 55 名年轻健康参与者进行了一系列执行任务的测试,评估了更新、转换和抑制功能,并创建了与每个功能相关的复合 z 分数。根据 COMT 基因和年龄(年轻、年老)衍生的遗传等位基因(Val/Val、Val/Met、Met/Met),将参与者分为 6 组。采用 t 检验和方差分析(p<0.05)评估年龄和基因型的影响。
老年组在三个执行过程中表现出较低的性能,特别是在抑制方面。此外,与年轻的 Val/Val 相比,携带 Val 等位基因的老年参与者在抑制复合测试中的表现较低。
这些结果证实了健康衰老中存在执行表现下降的现象。关于遗传效应,携带较低基础多巴胺水平(即 Val/Val 纯合子)的老年参与者似乎处于特别不利的地位,而这种水平在衰老过程中会进一步降低,并且当执行任务强调需要稳定的表现时(如抑制任务需要保持对不执行自动过程的指令的激活),他们的表现会更差。