Discusses specific mechanisms the cell uses to achieve longevity.
Cellular Maintenance and Repair
Death is of course inevitable, but, given the choice, most of us would rather die with the nervous system intact. Happily there are things one can do to retard the accumulation of damage (and, unhappily, things to advance it). The protein cycling diet supports one particular mechanism of cell repair, autophagy, but there are others that bear mention.
As mentioned it is the reactive oxygen species (ROS) produced by the oxygen-consuming energy-generating processes of the cell that likely do the most damage. The body produces or incorporates substances called anti-oxidants both within and without the cell to minimize their effects. One substance, ascorbate (vitamin C), is produced by most animals but not by humans and other members of the primate order of mammals. Because ascorbate was likely so plentiful in the natural diet of early primates, the necessary genes to complete its synthesis were lost and never regained. As a result we continue to require that the anti-oxidant, ascorbate, be obtained from the diet. Similarly the anti-oxidant tocopherol (vitamin E) must also be obtained from the diet. Many of the anti-oxidants produced by the body contain the element sulfur and sulfur in some available form must also be obtained from the diet.
The scientific studies on which the protein cycling diet are based are generally done with animals on diets deficient in only the substance under test. In consequence of modern dietary practices however, many people are border-line deficient in essential vitamins and minerals. To help the chances of getting the same results as the studies, daily supplementation with a full multi-vitamin and mineral tablet is recommended when on any diet. In particular ascorbate (vitamin C), tocopherol (vitamin E) and some source of sulfur (cysteine, SAMe, MSM, onions, etc.) should be provided. Other common border-line deficiencies in western industrial diets include omega-3 fatty acids, folic acid and magnesium and again supplementation is recommended.
Also one should refrain from substances that diminish anti-oxidant capacity such as foods high in iron and copper and acetaminophen (paracetamol).
Anti-oxidants may also prevent the accumulation of lipofuscin, a lipid-containing cellular condensate thought responsible for a number of neurodegenerative diseases called lipofuscinoses 5.
Perhaps the most important task of a cell to prolong its life is to protect its DNA, the blue-prints from which everything else is made. Higher cells keep their DNA locked up in a double-walled bubble called the nucleus. It is guarded by nuclear pores that only allow entrance to proteins that display certain sequences of amino-acids, the so-called nuclear location signals.
Within the nucleus a number of enzyme systems work tirelessly to repair any damage to the DNA itself. Also autophagy, a cell recycling process, has been seen to operate even on the nucleus to dispose of its garbage as will be extensively discussed later.
Cells perform much of their oxygen dependent metabolism within the mitochondria. A cell may have tens, hundreds or thousands of them. They contain their own DNA (mDNA) and protein synthesis system and must reproduce within the cell like the bacteria that evolutionarily they once were. Their DNA, like bacterial DNA, is not enclosed in a nucleus and is likely subject to more damage than if it were. Indeed most of the genes for the proteins of the mitochondria are in the host cell’s nucleus. Apparently the few proteins still encoded by the mitochondrial DNA are so difficult to transport that they justify the retention of a separate protein synthesis system in the mitochondria just so that the proteins can be assembled in place.
When its DNA is damaged, the mitochondrion will likely then be unable to reproduce or at least to reproduce as efficiently as before. The damage to the mDNA is then effectively removed as the damaged mitochondria are out-reproduced by the undamaged. Note that the cell must be growing or replacing itself before mitochondrial reproduction is needed. This point will also be discussed later in the context of autophagy.
The cell has a mechanism to selectively destroy individual proteins that are degraded – chaperone-mediated autophagy. When many proteins break down, they expose special amino-acid sequences that other proteins called chaperones can recognize. The chaperones then escort the degraded protein (and any object to which they may be attached) to a site in the cell where their amino-acids can be recycled. Note that this is not the form of autophagy that the protein cycling diet seeks to promote.
Protein turnover is a tightly-regulated essential cell function. It was once thought that after the cell had expended all the energy and effort required to build a large protein that it would be unreasonable that the cell would then destroy it before it had destroyed itself. Unreasonable but true nevertheless. Proteins actually signal their appropriate lifespans to the cell by the amino acid species on one end of the chain for times ranging between about 20 minutes to 20 hours accordingly. Nearly 100% of the amino acids of proteins can be recycled. Nevertheless losses from growth, reproduction, skin shedding and the digestive process are unavoidable and must be recovered from the diet.
There are proteins in the cell whose job is to attach chemical tags (ubiquitin) to any proteins they bump into. There are other protein complexes called proteasomes that chew up any proteins that have a lot of these tags attached. Without going into the mathematics, the net effect is that the proteins of the cell statistically have a fairly well determined life-span and are replaced when old whether they are degraded or not.
Proteins that form aggregates however may be able to escape the proteasomes even though they are extensively tagged with ubiquitine. The aggregate proves literally too large to fit into the proteasome’s mouth. These aggregates may however be dealt with by the forms of autophagy, macroautophagy and microautophagy, to be discussed in the next chapter and whose promotion is the purpose of the protein cycling diet.