Intermittent fasting is one way to reduce body fat that is increasing in popularity because it is so simple to do. But there are other advantages besides weight loss.
It has long been known that dietary restriction increases lifespan.
Whether it takes the form of reduced calories, reducing one of the nutrient types (protein, fat, or carbohydrate), or fasting occasionally (not eating for a day or two), dietary restriction has been shown to have beneficial effects in all manner of organisms, such as yeast, worms, flies, mice, monkeys, and humans.
When studying lifespan, it helps to work with organisms that have very short lifespans, where the effects of an intervention can be seen in the researcher’s lifetime. This is why much of the work has been done in short-lived species such as yeast, fruit flies, tiny worms, and mice. In these organisms, we see common mechanisms that dietary restriction triggers to increase lifespan, and we see those same mechanisms at work in longer lived animals, such as humans, even if we haven’t had time to collect a lot of data on actual lifespans.
Complicating the picture in humans is that not many have signed up for a lifetime of dietary restriction.
But recent work has shown that intermittent fasting causes the same changes in mitochondria that constant dietary restriction causes. And it is these changes in the mitochondria that are responsible for the extended lifespans.
This is very good news, as skipping a few meals every now and then is something people can do easily, and many people are already doing it, for a number of reasons, not the least of which is that it is an effective weight-loss technique. That it might also make you live a longer and healthier life is definitely a plus.
This life-extension benefits of intermittent fasting happen even if the organism is not overweight, so it is separate from the health benefits of avoiding obesity.
Besides dietary restriction, the antibiotic rapamycin has also been shown to increase lifespan in yeast, fruit flies, and mice.
In studying the effects of rapamycin, a metabolic pathway called TOR (short for ‘Target Of Rapamycin’) was found. Rapamycin inhibits TOR. TOR, in turn, inhibits messenger RNA, the molecule that translates the DNA code into protein. So rapamycin increases messenger RNA, thus increasing protein production in cells.
It turns out that dietary restriction and intermittent fasting decreases protein production in cells (as you might expect), except for in the mitochondria, where it actually increases protein production.
It is this increase in mitochondrial protein production that is one of the keys to longevity.
Another key is autophagy, which is a kind of basic housekeeping that cells do (it means ‘eating oneself’). Older, damaged parts of the cell are recycled for their nutrients, and replaced by new undamaged parts.
As it turns out, dietary restriction increases autophagy, through a mechanism involving the TOR pathway.
We are beginning to see a pattern here.
A particular form of autophagy affects mitochondria. Unsurprisingly, it is called mitophagy. Youthful mitochondria fuse together, but as they age they can toggle into fragmented states. In their youthful, fused state, mitochondria extend lifespan by communicating with organelles in the cell called peroxisomes to control fat metabolism. This is described more fully in a recently published paper.
Thus lifespan and energy metabolism are closely linked.
The central molecule in metabolism is adenosine triphosphate (ATP).
ATP is the molecule created when we digest food. It is used in cells as an energy source, where its phosphates are removed one at a time, extracting energy from the molecule with each one. The resulting molecules are adenosine diphosphate (ADP) and adenosine monophosphate (AMP).
Because this molecule is central to all life, there are a lot of signalling molecules that interact with ATP and with AMP. One of these molecules is the enzyme AMP-activated protein kinase (AMPK).
The paper discussing mitochondria and lifespan points out that they could increase lifespan either by intermittent fasting, or by tinkering with an organism’s genes for AMPK.
As the name implies, AMPK is activated by AMP. As ATP is used to provide energy to cells, the depleted form, AMP, builds up, and activates AMPK. AMPK is thus a cellular energy sensor, responding to low levels of ATP (i.e. high levels of AMP).
Low glucose levels activate AMPK. So does low oxygen (hypoxia), since oxygen is needed to burn food to produce ATP. Inadequate blood supply (ischemia) can cause low glucose and oxygen levels, and thus activate AMPK. Changes in calcium levels caused by exercise also activate AMPK.
It is by activating AMPK that the hormone adiponectin increases glucose and fatty acid burning, an effect covered in detail in Gut Reactions.