Vitamin C, Aging and Alzheimer’s Disease

Abstract

Accumulating evidence in mice models of accelerated senescence indicates a rescuing role of ascorbic acid in premature aging. Supplementation of ascorbic acid appeared to halt cell growth, oxidative stress, telomere attrition, disorganization of chromatin, and excessive secretion of inflammatory factors, and extend lifespan. Interestingly, ascorbic acid (AA) was also found to positively modulate inflamm-aging and immunosenescence, two hallmarks of biological aging. Moreover, ascorbic acid has been shown to epigenetically regulate genome integrity and stability, indicating a key role of targeted nutrition in healthy aging. Growing in vivo evidence supports the role of ascorbic acid in ameliorating factors linked to Alzheimer’s disease (AD) pathogenesis, although evidence in humans yielded equivocal results. The neuroprotective role of ascorbic acid not only relies on the general free radical trapping, but also on the suppression of pro-inflammatory genes, mitigating neuroinflammation, on the chelation of iron, copper, and zinc, and on the suppression of amyloid-beta peptide (Aβ) fibrillogenesis. Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease is rapidly increasing. Thus, dietary interventions, as a way to epigenetically modulate the human genome, may play a role in the prevention of AD. The present review is aimed at providing an up to date overview of the main biological mechanisms that are associated with ascorbic acid supplementation/bioavailability in the process of aging and Alzheimer’s disease. In addition, we will address new fields of research and future directions.

Protective effect of Kumquat fruits and carrot seeds extracts against brain aging in rats

“…Additionally, kumquat according to Hosseini et al (38) is a good source of vitamin C to which the protective effect of kumquat fruits against brain aging may be attributed. Monacelli et al (39) declared that oxidative stress, over production of the inflammatory agents, telomere attrition, as well as chromatin disorganization can be suppressed by vitamin C. Also, the two hallmarks of biological aging (immune-senescence and inflammaging) can be modulated by vitamin C. Mani and Parle (40) concluded that the elevation in acetyl cholinesterase activity and the memory deficits can be reversed by the oral administration of carrot seeds extract. Mani et al (41) suggested the beneficial effect of carrot seeds in Alzheimer's disease.…”

Metabolic Biomarkers of Ageing in C57BL/6J Wild-Type and Flavin-Containing Monooxygenase 5 (FMO5)-Knockout Mice

“…The level of ascorbate was increased from 15 to 30 weeks in both FMO5 KO and WT mice and then decreased in WT mice as they age from 30 to 45 weeks while it remained stable in KO mice. Ascorbate is known to be helpful in preventing or delaying the progression of ageing and age-related disease (Monacelli et al, 2017 ). Iwama et al ( 2012 ) reported decreased ascorbate concentration in the urine of C57BL/6 mice as they aged from 6 to 30 months and suggested that ascorbate-synthesizing ability decreases over time are a key element in age-related diseases (Iwama et al, 2012 ).…”

Neuroprotective Natural Molecules, From Food to Brain

“…Low levels of VitC and VitE, as well as other antioxidants, have been observed in plasma of individuals with Alzheimer’s disease and mild cognitive impairment ( Rinaldi et al, 2003 ; Mangialasche et al, 2012 ), which has led to the suggestion that supplementation with antioxidants could delay or reduce cognitive impairment. The results of the several trials that have already been carried out in the last decades failed to reach a consensus by the role of these vitamins in the treatment of aging and related disease ( Petersen et al, 2005 ; Goodman et al, 2011 ; Santilli et al, 2015 ; Basambombo et al, 2017 ; Monacelli et al, 2017 ; Ohlow et al, 2017 ). This can be due, at least in part, to the heterogeneity (e.g., genetic variations as well as differences in diet, lifestyle and environmental factors) of the human population and the difficulty in finding true controls ( Mocchegiani et al, 2014 ), as well as the inherent variability in amounts of VitE present in regular diets.…”