cognitive fun!

great point, post more.

i actually tried that for a few weeks (first year of med school)... trying to double caloric intake (or so) every other day. it was not easy and i lost weight rapidly; unsustainable for me.

apparently IF reduces nmda type 2b receptor downregulation and/or enhances its expression, a huge cognitive player

either way, papers now suggest that the majority of the benefit of caloric restriction has to do with protein restriction, more specifically methionine restriction, which may account for most of the ROS reduction formerly attributed to caloric restriction (which is probably not feasible for most people).

whether methionine restriction imparts cognitive gains remains unexplored as far as i know... time'll tell.

im still unsure how to even eat a met-R diet.

Rejuvenation Res. 2009 Dec;12(6):421-34.
Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria.

Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, López-Torres M, Pamplona R, Barja G.

Department of Animal Physiology II, Complutense University of Madrid, Madrid, Spain.

Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty acid unsaturation in rat liver. Mitochondrial ROS generation and the degree of fatty acid unsaturation are the only two known factors linking oxidative stress with longevity in vertebrates. However, it is unknown whether 40% MetR, the relevant methionine restriction degree to clarify the mechanisms of action of standard (40%) DR can reproduce these effects in mitochondria from vital tissues of strong relevance for aging. Here we study the effect of 40% MetR on ROS production and oxidative stress in rat brain and kidney mitochondria. Male Wistar rats were fed during 7 weeks semipurified diets differing only in their methionine content: control or 40% MetR diets. It was found that 40% MetR decreases mitochondrial ROS production and percent free radical leak (by 62-71%) at complex I during forward (but not during reverse) electron flow in both brain and kidney mitochondria, increases the oxidative phosphorylation capacity of brain mitochondria, lowers oxidative damage to kidney mitochondrial DNA, and decreases specific markers of mitochondrial protein oxidation, lipoxidation, and glycoxidation in both tissues. Forty percent MetR also decreased the amount of respiratory complexes I, III, and IV and apoptosis-inducing factor (AIF) in brain mitochondria and complex IV in kidney mitochondria, without changing the degree of mitochondrial membrane fatty acid unsaturation. Forty percent MetR, differing from 80% MetR, did not inhibit the increase in rat body weight. These changes are very similar to the ones previously found during dietary and protein restriction in rats. We conclude that methionine is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in DR.

J Neurosci. 2007 Sep 19;27(38):10185-95.
Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor.

Fontán-Lozano A, Sáez-Cassanelli JL, Inda MC, de los Santos-Arteaga M, Sierra-Domínguez SA, López-Lluch G, Delgado-García JM, Carrión AM.

División de Neurociencias, Universidad Pablo de Olavide de Sevilla, 41013 Sevilla, Spain.

One of the main focal points of aging research is the search for treatments that will prevent or ameliorate the learning and memory deficiencies associated with aging. Here we have examined the effects of maintaining mature mice on a long-term intermittent fasting diet (L-IFD). We found that L-IFD enhances learning and consolidation processes. We also assessed the long-term changes in synaptic efficiency in these animals. L-IFD mice showed an increase in low-theta-band oscillations, paired-pulse facilitation, and facilitation of long-term synaptic plasticity in the hippocampus with respect to mice fed ad libitum. In addition, we found an increase in the expression of the NMDA receptor subunit NR2B in some brain areas of L-IFD mice. Specific antagonism of this subunit in the hippocampus reversed the beneficial effects of L-IFD. These data provide a molecular and cellular mechanism by which L-IFD may enhance cognition, ameliorating some aging-associated cognitive deficits.