Abstract
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.
Highlights
The incidence of neurodegenerative disorders including Alzheimer’s disease (AD) is increasing rapidly with the extension of average life expectancy [1]
There were an age-matched senescence-accelerated mouse resistant 1 (SAMR1) control group (Con-R) and a young senescence-accelerated mouse prone 8 (SAMP8) control group (Con-Y), both of which were fed with folic acid (FA)-normal diet
FA-normal diet (FA-N), Con-R and Con-Y groups were all fed with FAnormal diet, and there is no significant difference in folate (Figure 1A and 1B) or Hcy (Figure 1C and 1D) concentrations among them
Summary
The incidence of neurodegenerative disorders including Alzheimer’s disease (AD) is increasing rapidly with the extension of average life expectancy [1]. Folate is important for the functioning of the nervous system at all ages [6]. It provides nucleotide precursors www.aging-us.com and maintains homocysteine (Hcy) at non-toxic levels through one-carbon metabolism [7]. Excessive levels of reactive oxygen species (ROS), and DNA damage [8,9,10]. Brain neurons become susceptible to ROSinduced DNA damage if antioxidants are depleted [11]. Perhaps through this mechanism, transgenic mouse models of AD exhibited increased cellular DNA damage and hippocampal neurodegeneration when maintained on a folic acid (FA)-deficient diet [12]. Poor cognitive performance is associated with low serum folate concentration [13], whereas FA supplementation appears to improve cognitive function especially in people with mild cognitive impairment [14, 15]
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