State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Sci China Life Sci. 2010 Dec;53(12):1399-404. doi: 10.1007/s11427-010-4112-3. Epub 2010 Dec 23.
Formaldehyde, one of the most toxic organic compounds, is produced and processed in human cells. The level of human endogenous formaldehyde is maintained at a low concentration (0.01-0.08 mmol L(-1) in blood) under physiological conditions, but the concentration increases during ageing (over 65 years old). Clinical trials have shown that urine formaldehyde concentrations are significantly different between elderly Alzheimer's patients (n=91) and normal elderly volunteers (n=38) (P<0.001). Abnormally high levels of intrinsic formaldehyde lead to dysfunction in cognition such as learning decline and memory loss. Excess extracellular and intracellular formaldehyde could induce metabolic response and abnormal modifications of cellular proteins such as hydroxymethylation and hyperphosphorylation, protein misfolding, nuclear translocation and even cell death. This cellular response called formaldehyde stress is dependent upon the concentration of formaldehyde. Chronic impairments of the brain resulted from formaldehyde stress could be one of the mechanisms involved in the process of senile dementia during ageing.
甲醛是毒性最大的有机化合物之一，在人体细胞中产生和加工。在生理条件下，人体内源性甲醛的水平维持在低浓度（血液中 0.01-0.08mmol/L），但在衰老过程中（65 岁以上）浓度会增加。临床试验表明，老年阿尔茨海默病患者（n=91）与正常老年志愿者（n=38）的尿甲醛浓度有显著差异（P<0.001）。内在甲醛水平异常升高会导致认知功能障碍，如学习能力下降和记忆力减退。过多的细胞外和细胞内甲醛会诱导代谢反应和细胞蛋白质的异常修饰，如羟甲基化和过度磷酸化、蛋白质错误折叠、核转位，甚至细胞死亡。这种细胞反应称为甲醛应激，取决于甲醛的浓度。甲醛应激导致的大脑慢性损伤可能是衰老过程中老年痴呆症发生机制之一。
