I’ve written a lot about intermittent fasting and how it is a uniquely healthful practice. One of the main reasons for this is that it enables the process of autophagy to be upregulated. Autophagy, which comes from the Greek for “self-eating” is the regulated process of cellular self-cleaning which occurs on a daily basis in all healthy cells. Autophagy normally proceeds at a low, basal level during the fed state, but fasting causes it to increase; this makes sense from a mechanistic point of view, since one of the reasons for autophagy is to provide the body with nutrients when food is unavailable. The main nutrients provided are amino acids, which autophagy produces when proteins are broken down.
That autophagy is self-cleaning can be seen in the fact that cellular “junk”, that is, misfolded proteins, organelles such as mitochondria that have passed their sell-by date, as well as viruses and bacteria are the first things to go when autophagy increases. In this way, autophagy keeps cells in their efficient, youthful state, and thus retards aging. It’s been shown that cells from long-lived individuals, i.e. centenarians, have higher rates of autophagy than the merely old (75 years). Conversely, diminished autophagy plays a major role in aging. Maintaining clean cells is important to slowing aging.
I noted recently that most people used to do intermittent fasting all the time, without knowing it. The reason for this is that, until the advent of refrigerators and later, fast and convenience food, most people would eat dinner in the evening and then have nothing else to eat until breakfast, so a fast of maybe 12 hours was normal. It happens that autophagy is strongly increased at night because of this fasting. Both the more-than-usual provision of food, as well as aging, will cause the process of autophagy to decrease and to occur less often.
As mentioned, one consequence of autophagy besides the maintenance of “clean” cells is providing amino acids to the bloodstream and thus the rest of the body during fasting, when food is unable to do so. The main signal for autophagy to start and to increase is decreased concentration of the amino acid leucine in the blood. Readers may recognize leucine as a key signaling molecule for the growth of muscle; the opposite occurs with leucine too, namely decreased concentration signals for muscle to be broken down.
One of the more important amino acids besides leucine that increases in the blood during autophagy is cysteine, which is the key component of the important tripeptide glutathione. The main function of glutathione is to protect cells against oxidative stress by eliminating free radicals, aka reactive oxygen species; it is the body’s most important internal antioxidant. In aging, oxidative stress increases, and glutathione levels decrease, and this is so characteristic of aging that some have even asked whether aging is a cysteine deficiency syndrome, on the basis that declining levels of cysteine mean lower glutathione levels, which mean greater oxidative stress.
So, if you’re with me so far, as we age, the process of autophagy, which is turned on and off by blood leucine levels, dimishes in power, meaning that less cysteine is provided during periods of fasting, causing lower glutathione levels, lower antioxidant capacity, and increased oxidative stress.
Here’s the one weird trick. As mentioned, autophagy is regulated by levels of leucine in the blood, but in aging, the ability to respond to leucine by increasing autophagy decreases. The cells in an aging body simply cannot turn autophagy on at the same level that would turn it on in youthful cells. the trick: decrease levels of leucine during the fasting phase so that even with diminished autophagy capacity, autophagy is started.
How do you do this? Very simple: drink water at night. This will dilute the bloodstream and hence the leucine in it, causing autophagy to be started and/or increased. Thus more cysteine will enter the blood, glutathione will be made from it, and oxidative stress decreased.