The molecular neural mechanism underlying the acceleration of brain aging due to Dcf1 deficiency

被引：0

作者：

Zhou, Haicong ^{[1
,2
]}

Wang, Jiao ^{[2
]}

Wen, Tieqiao ^{[2
,3
]}

机构：

[1] Shanghai Univ, Sch Environm & Chem Engn, Shanghai, Peoples R China

[2] Shanghai Univ Shanghai, Sch Life Sci, Lab Mol Neural Biol, Shanghai, Peoples R China

[3] Shanghai Univ, Sch Life Sci, 333 Nanchen Rd, Shanghai 200444, Peoples R China

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2023年 / 126卷

基金：

中国国家自然科学基金;

关键词：

Aging; Neurogenesis; Senescence factor; Dcf1; STEM-CELLS; ADULT NEUROGENESIS; PROGENITOR CELLS; LIFE-SPAN; SENESCENCE; DAMAGE; PI3K/AKT/FOXO3A; DEGRADATION; PATHWAY; GROWTH;

D O I：

10.1016/j.mcn.2023.103884

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Owing to the continuous increase in human life expectancy, the management of aging-related diseases has become an urgent issue. The brain dominates the central nervous system; therefore, brain aging is a key area of aging-related research. We previously uncovered that dendritic cell factor 1 (Dcf1) maintains the stemness of neural stem cells and its expression in Drosophila can prolong lifespan, suggesting an association between Dcf1 and aging; however, the specific underlying neural mechanism remains unclear. In the present study, we show for the first time that hippocampal neurogenesis is decreased in aged Dcf1-/- mice, which leads to a decrease in the number of brain neurons and an increased number of senescent cells. Moreover, astrocytes proliferate abnormally and express elevated mRNA levels of aging-related factors, in addition to displaying increased activation of Akt and Foxo3a. Finally, behavioral tests confirm that aged Dcf1-/- mice exhibit a significant decline in cognitive abilities related to learning and memory. In conclusion, we reveal a novel mechanism underlying brain aging triggered by Dcf1 deficiency at the molecular, cellular, tissue, and behavioral levels, providing a new perspective for the exploration of brain aging.

引用

页数：11