Research Paper Volume 11, Issue 22 pp 10356—10373
Folic acid delays age-related cognitive decline in senescence-accelerated mouse prone 8: alleviating telomere attrition as a potential mechanism
- 1 Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China
- 2 Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China
- 3 Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA
- 4 Department of Rehabilitation Medicine, Tianjin Medical University, Tianjin 300070, China
received: July 16, 2019 ; accepted: November 8, 2019 ; published: November 22, 2019 ;https://doi.org/10.18632/aging.102461
How to Cite
Copyright © 2019 Lv et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The occurrence of telomere attrition in brain may cause senescence and death of neurons, leading to cognitive decline. Folic acid (FA) has been reported to improve cognitive performance in mild cognitive impairment; however, its association with telomere remains unclear. The study aimed to investigate if alleviation of telomere attrition by FA supplementation could act as a potential mechanism to delay age-related cognitive decline in senescence-accelerated mouse prone 8 (SAMP8). Aged SAMP8 mice were assigned to four treatment groups: FAdeficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group and high FAsupplemented diet (FA-H) group. There was also an age-matched senescence-accelerated mouse resistant 1 (SAMR1) control group (Con-R), and a young SAMP8 control group (Con-Y). The results demonstrated that FA supplementation delayed age-related cognitive decline and neurodegeneration in SAMP8 mice. Importantly, this effect could be attributed to the alleviated telomere attrition, which might be interpreted by the decreased levels of reactive oxygen species. Additionally, improved telomere integrity stimulated mitochondrial function via telomere-p53-mithondria pathway, consequently delayed neuronal degeneration. In conclusion, we demonstrate that FA supplementation delays age-related neurodegeneration and cognitive decline in SAMP8 mice, in which alleviated telomere attrition could serve as one influential factor in the process.
AD: Alzheimer’s disease; BCA: bicinchoninic acid; FA: folic acid; FJB: Fluoro-Jade B; FPG: formamidopyrimidine DNA-glycosylase; Hcy: homocysteine; HE: hematoxylin and eosin; HK2: Hexokinase 2; HO: hydroxyl free radical; mtDNA: mitochondrial DNA; MWM: Morris water maze; nDNA: nuclear DNA; Nrf1: nuclear respiratory factor 1; O2–: superoxide anion free radical; OF: open field; PGC-1α: peroxisome proliferator-activated receptor γ coactivator 1α; SAMP8: senescence-accelerated mouse prone 8; SAMR1: senescence-accelerated mouse resistant 1; RBC: red blood cell; ROS: reactive oxygen species; Tfam: mitochondrial transcription factor A; 8-OHdG: 8-hydroxy-2'-deoxyguanosine.