Intermittent fasting improves long-term memory retention and promotes hippocampal neurogenesis

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A new study from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London has established that Intermittent Fasting (IF) is an effective means of improving long term memory retention and generating new adult hippocampal neurons in mice, in what the researchers hope has the potential to slow the advance of cognitive decline in older people.

The study, published today in Molecular Biology, found that a calorie restricted diet via every other day fasting was an effective means of promoting Klotho gene expression in mice. Klotho, which is often referred to as the “longevity gene” has now been shown in this study to play a central role in the production of hippocampal adult-born new neurons or neurogenesis.

Adult-born hippocampal neurons are important for memory formation and their production declines with age, explaining in part cognitive decline in older people.

The researchers split female mice into three groups; a control group that received a standard diet of daily feeding, a daily Calorie Restricted (CR) diet, and Intermittent Fasting (IF) in which the mice were fed every other day. The latter two groups were fed 10% less calories than the control.

Over the course of three months, the mice in the IF group demonstrated improved long-term memory retention compared to the other groups. When the brains of these mice were studied, it was apparent that the Klotho gene was upregulated, and neurogenesis increased compared to those that were on the CR diet.

“We now have a significantly greater understanding as to the reasons why intermittent fasting is an effective means of increasing adult neurogenesis. Our results demonstrate that Klotho is not only required, but plays a central role in adult neurogenesis, and suggests that IF is an effective means of improving long-term memory retention in humans.” Said Dr Sandrine Thuret, of King’s IoPPN.

Dr Thuret’s previous work has demonstrated that calorie restricted diets in humans can improve memory function. That research showed that IF can enhance learning processes and could affect age associated cognitive impairment.

Dr Gisele Pereira Dias from King’s IoPPN said “In demonstrating that IF is a more effective means of improving long term memory than other calorie-controlled diets, we’ve given ourselves an excellent means of going forwards. To see such significant improvements by lowering the total calorie intake by only 10% shows that there is a lot of promise.”

The researchers now hope to recreate this study with human participants in order to further explore the effects of IF.

Funding: This study was made possible thanks to funding from the Medical Research Council (UK), the Psychiatry Research Trust, and the AHA-Allen Initiative in Brain Health and Cognitive Impairment.


Neurodegenerative diseases, a heterogeneous group of disorders, are characterized by slow progressive loss of neurons [1]. Although the precise etiology underlying neurodegeneration has not been fully elucidated, oxidative stress has been suggested as one of the contributing factors of various neurodegenerative diseases and accelerated aging [2,3,4,5].

Levels of oxidative damage correlate significantly with the neurodegenerative impairment in various populations. For these reasons, there is a great interest among researchers in finding ways to protect against oxidative damage and potentially treat neurodegenerative diseases, especially among individuals with mild cognitive impairment (MCI).

MCI is a pre-stage for dementia, and it is known to be reversible. Previous research has reported that MCI is associated with impairment of glucose metabolism in the brain, dietary composition, and caloric intake [6].

Dietary approaches are suggested as more viable and non-invasive ways to prevent MCI incidence and to promote the reversion of MCI among the general public. Caloric restriction (CR) is one of the dietary regimens that have been shown to produce positive health effects.

However, several alternative hypotheses argued that CR could cause damage to protein, lipids, and nucleic acids through the accumulation of reactive oxygen species (ROS) or reactive nitrogen species (RNS) [7].

Moreover, the compliance to long-term hypocaloric diet is inadequate, and other approaches more acceptable from the older adult perspective are needed. Thus, intermittent fasting (IF) is another approach that represents an alternative and more physiological way to prevent the deleterious effect of chronic excess of food intake [8].

IF is an umbrella term referring to various dietary regimens that cycle between a period of non-fasting and a period (long or short) of total fasting [9]. IF was intended as an alternative regimen that takes advantage of CR benefits, without eliciting any negative side effects from severe CR that causes malnourishment. Several studies support the idea that IF and CR activate similar biological mechanisms [10].

Interestingly, IF also reduces body weight the same as CR, but the difference is that CR produces loss of muscle mass and adipose tissue whereas IF reduces the adipose tissues whilst preserving muscle mass both in human and animal models [11].

Many scientific studies have been carried out, finding that IF gives beneficial health improvement by prolonging the lifespan and prevention of other chronic diseases including cardiovascular diseases, different forms of cancer, diabetes, and renal diseases [12,13].

Although previous studies have demonstrated the beneficial effects of IF with or without CR amongst an older population, most of these studies focused on healthy and obese people with no or limited MCI only.

Fasting CR conducted among older adult men for 3 months via a clinical trial using a combination regime of CR with 2 days/weeks of Muslim sunnah fasting showed that CR with IF could improve metabolic parameters and quality of life, and alleviate the depression among these older subjects [12].

IF was also reported as one of the factors for reducing the risk of cognitive impairment among older adults in a large cohort conducted in Malaysia [14]. For these reasons, there is a need to identify the health benefits of IF among older adults with MCI.

Hence, this study aims to investigate the effects of IF on biochemical profile, cognitive function, oxidative stress, genome health, and inflammatory responses among older adults with MCI. Besides this, this study also aims to identify the neuroprotective metabolites among older adults with MCI who practice IF since the human metabolomics data on this aspect remain unavailable.

Conclusions

In conclusion, the MCI-afflicted older adults who practiced IF regularly had better cognitive scores and reverted to better cognitive function groups (successful aging and normal aging) at 36 months follow-up. This study revealed that IF can offer similar benefits as compared to CR and other fasting diets.

Furthermore, our current findings also suggest that IF could be a better solution to combat the cognitive impairment that occurs during the aging process since IF is more applicable and easy to practice, especially among older adults and people under clinical intervention.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551340/


Original Research: Open access.
Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho” by Gisele Pereira Dias, Tytus Murphy, Doris Stangl, Selda Ahmet, Benjamin Morisse, Alina Nix, Lindsey J. Aimone, James B. Aimone, Makoto Kuro-O, Fred H. Gage, Sandrine Thuret. Molecular Biology

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