Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats

Abstract

Lifelong dietary restriction (DR) is known to have many potential beneficial effects on brain function as well as delaying the onset of neurological diseases. In the present investigation, the effect of late-onset short-term intermittent fasting dietary restriction (IF-DR) regimen was studied on motor coordination and cognitive ability of ageing male rats. These animals were further used to estimate protein carbonyl content and mitochondrial complex I-IV activity in different regions of brain and peripheral organs, and the degree of age-related impairment and reversion by late-onset short-term IF-DR was compared with their levels in 3-month-old young rats. The results of improvement in motor coordination by rotarod test and cognitive skills by Morris water maze in IF-DR rats were found to be positively correlated with the decline in the oxidative molecular damage to proteins and enhanced mitochondrial complex IV activity in different regions of ageing brain as well as peripheral organs. The work was further extended to study the expression of synaptic plasticity-related proteins, such as synaptophysin, calcineurin and CaM kinase II to explore the molecular basis of IF-DR regimen to improve cognitive function. These results suggest that even late-onset short-term IF-DR regimen have the potential to retard age-associated detrimental effects, such as cognitive and motor performance as well as oxidative molecular damage to proteins.

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

“…Different variants of intermittent energy restriction (CR for intermittent periods of time) have been reported to have health‐promoting effects. These beneficial health effects include improvements of body composition 12, 13, 14, skin wound healing 9, blood pressure and cardiovascular health markers 15, 16, neurological health and cognitive performance 17, 18, 19 and retarded tumor growth/formation 20, 21, 22, 23. By applying repetitive cycles of fasting/CR and regular eating, the negative side effects of CR are thought to be circumvented.…”

Intermittent fasting favored the resolution of Salmonella typhimurium infection in middle-aged BALB/c mice

“…A late-onset intermittent fasting protocol was chosen for this study because it provides greater benefits than an early-onset protocol in regard to retarding the ageassociated detrimental effects ascribed to oxidative damage (Singh et al 2012).…”

“…The experimental protocol for intermittent fasting in rodents consists of alternate days of ad libitum feeding and food deprivation for three or more months (Anson et al 2003;Duan et al 2001;Singh et al 2012). As a result of this protocol, the cellular stress response reportedly triggers the production of proteins that protect against age-associated detrimental effects of oxidative damage (Li et al 2013).…”

Old-onset caloric restriction effects on neuropeptide Y- and somatostatin-containing neurons and on cholinergic varicosities in the rat hippocampal formation

“…It was already known that moderate caloric restriction in adult rats did not lead to gross morphological alterations in the brain, even in chronic treatments (Andrade et al 2002;Cardoso et al 2013), although subtle neuronal changes, such as dendritic alterations, were described (Andrade et al 2002). However, there are few studies that analyzed if the caloric restriction would be capable to promote morphological and functional changes when started in advanced age (Kim and Choi 2000;Adams et al 2008;Del Arco et al 2011;Singh et al 2012), a period where the brain is particularly vulnerable to environmental aggressions . As follows, at a gross morphological level, the present results Fig.…”