Saturday 7 July 2018

Anti-ageing through regular fasting

Delaying the ageing process is a ‘hot’ subject of research. Over the past ten years, numerous studies have been carried out into the effect of fasting, also known as calorie restriction. But exactly what happens at the cellular level?

A study has revealed that a calorie-restricted diet can prolong life. However, the extreme variations of fasting are reserved for just very few people. A form of fasting that does work for many people is intermittent fasting, where normal meals are eaten for five days and approximately 300 calories for two days. This will alleviate the worst of the hunger.


Health benefits

Animal studies have shown that calorie restriction prolongs life and delays degenerative ageing processes. Calorie restriction also has numerous health benefits in people. Insulin sensitivity increases and obesity, oxidative stress and low-grade inflammatory processes decrease, non-functional (i.e.: potentially dangerous) cells are cleared up and regeneration processes improve. 
The question now is exactly what happens at cell and molecular level? Other questions that arise are what effect calorie restriction has on stem cells and can the beneficial effects of calorie restriction be boosted naturally? 


Stem cell research

The stem cells hold one of the keys to extending life. A recent study has revealed that calorie restriction can reverse the regenerative capacity of stem cells. The study performed at the leading Massachusetts Institute of Technology (MIT) reveals that loss of stem cell function, which is an inherent part of ageing, is reversable by fasting for 24 hours. The scientists discovered that, in mice, fasting significantly improved the regenerative capacity of the stem cells. That didn’t only apply to the younger mice but to the older mice too. 
Stem cells occur in different places in the body. For example, the bone marrow is a source of stem cells, where new (different) blood cells grow. The intestinal tract also contains adult stem cells that give rise to replacement of all new intestinal cells. As is the case for all (adult, non-embryonic) stem cells, the regenerative capacity of the intestinal stem cells decreases as the years go by. As a result of this, recovery from gastrointestinal infections and/or other disorders involving the intestines is almost impossible 
Intestinal epithelial cells form the lining of the intestinal wall. These cells usually renew themselves every five days. When an injury or infection occur, through cell division the stem cells give rise to renewal. The older people become, the more this regenerative capacity reduces, meaning it will take the intestinal wall longer to recover. Intestinal stem cells are, as it were, the work horses of the intestine that give rise to more stem cells and to different types of intestinal cells. The North American researchers mainly focussed on being able to understand how calorie restriction improves the function of young and old intestinal stem cells during a 24-hour period.


Striking regeneration capacity

After mice had fasted for 24 hours, the researchers removed intestinal stem cells and allowed these to grow in a culture dish, allowing them to determine whether the cells may give rise to ‘mini intestines’ that are known as organoids. The researchers discovered that the stem cells of fasting mice, that had fasted for 24 hours, had double regeneration capacity. 


Metabolic switch

Molecular research showed that the stem cells isolated from the mice that had fasted for 24 hours switched to a different fuel source. When fasting, these stem cells utilised fatty acids instead of glucose, which would be normal in an anabolic state. The researchers determined this by determining the order of the messenger RNA, isolated from the stem cells of the mice that had fasted for 24 hours. In short: a metabolic switch provokes stem cells to change to utilising fatty acid, resulting in an improvement in the regenerative capacity. 

Silent information regulator proteins (SIRT) and resveratrol

Other molecular research shows that calorie restriction (lowering the energy intake to approximately 60 percent, with an optimum nutrient intake) activates a group of enzymes (the sirtuins). An interesting aspect is that sirtuins (SIRT 1-7) play a role in influencing a wide range of cellular processes: ageing, programmed cell death (apoptosis), inflammations, resistance to stress, as well as dealing efficiently with energy. In addition, sirtuins can also regulate circadian processes and mitochondrial biogenesis. 
As well as calorie restriction, there are also ingredients in vegetables, fruit and herbs that influence the production of sirtuins. A known stimulator of, amongst other things, SIRT1 is the resveratrol that occurs naturally in grapes and wine. Animal studies have shown that supplementation with resveratrol is beneficial in delaying ageing processes through its effect on SIRT1. It also improves glucose tolerance and insulin-sensitivity in the liver and muscle tissue. 
Other health benefits of resveratrol include improved energy metabolism and a protective effect on the heart and blood vessels. Stilbenoids associated with resveratrol are classified under the salvestrols that have comparable effects. This is why (colourful) plant-based food, full of phytonutrients, is so healthy to eat.



To summarise, it appears that calorie restriction extends life. This is because stem cells switch to utilising fatty acids. Other mechanisms relate to activation of a group of proteins that are called sirtuins. These can be activated by resveratrol.