Lou Dischler writing excerptsó
HOW TO REVERSE AGING
It is possible to reverse the aging process. I know because I have done it. To understand how, one must first understand where aging comes from.
Aging is primarily epigenetic
The most currently compelling hypothesis is that aging of an organism reflects the aging of cells, and aging of cells is due to the scrambling of their epigenetic codes.
The genetic code resides in the DNA, while the epigenetic code resides above the DNA and determines which genes are turned on or off. This brilliant innovation allows an organism with one genetic code shared by all cells to generate more than one cell type and thus become more than a blob of jelly. Humans have more than 200 cell types, all distinguished epigenetically.
The epigenetic code has poor fidelity, unfortunately. It collects errors some ten times faster than the underlying DNA. These epimutations result in synthesis of the wrong mix of proteins. Cells might be quite happy making anything on their genetic menu, but the organ systems in which they reside arenít happy. Function declines and the organism ages. Thus evolution puts expiration dates on cells so they can be removed before they got too dysfunctional. These are the telomeres, the repeating sequences of nucleic acids that cap the strands of DNA. Each time a cell divides, its telomeres erode like a fuse burning down, and eventually it is slated for recycling by the process of programmed suicide called apoptosis.
As a second benefit, sell-by dates reduce the incidence of cancer.
Epigenetic and telomeric clocks
There are two types of relatively rapid DNA aging ó epigenetic and telomeric. These clocks run independently, but there is sufficient correlation on a cellular level that eliminating telomerically old cells reduces the average epigenetic age of the organism.† Many have gotten the erroneous idea that stimulating the enzyme telomerase to lengthen telomeres will confer longer life. But this is cheating. Itís like slapping new sell-by dates on cans of meat on a grocery store shelf. It keeps the cans on the shelf longer, sure, but it doesnít change the spoilage going on inside.
Just as itís best to discard expired cans, itís best to eliminate expired cells. Once they become senescent, they contribute nothing to organ function, and worse, they excrete toxic chemical signals. The field of senolytics has sprung up to eliminate senescent cells that arenít eliminated naturally, but it isnít sufficient just to get rid of them. They must be replaced. And the replacements come from stem cells.
The body has trillions of somatic cells that are fully programmed for one of the roughly 200 cell types. They all derive from the much less numerous stem cells. These stem cells come in several types that range from unprogrammed to partially programed.
Types of stem cells
Totipotent cells are the most versatile. They can become any cell in the body or placenta, but disappear early in fetal development. Embryonic cells are pluripotent and can become any cell type except placental. Adult stem cells are multipotent and can replace a restricted set of somatic cells. Transit amplifying cells (TACs) are intermediaries between stem cells and somatic cells. They do most of the dividing and are thus subject to the most rapid aging.
While it was once thought that embryonic cells disappeared in the adult, recently it was discovered they still exist in the form of very small embryonic-like stem cells (VSELs) that circulate in the blood and serve as a backup for adult stem cells that themselves are a backup for TACs .
Somatic cells typically produce no telomerase and thus age telomerically. Adult stem cells produce telomerase, but not enough to completely stop telomeric aging, while it appears VSELs produce enough telomerase to be immortal. Thus stimulating VSELs will keep the other niches filled with epigenetically young stem cells. Eliminating senescent cells and replacing them via replenished stem cells and TACs will then eliminate or reverse epigenetic aging.
Epigenetic age is an average, as organs contain both old and young cells, with the average age climbing relentlessly as the rate of replacement declines. The aging of individual cells cannot be stopped, even though treatments can reverse the average age by increasing the replacement rate.
Filling stem cell niches using mitochondrial switches
The first hurdle in reversing the average age is in restocking the stem cell niches, which become depleted with age. This can be done endogenously by stimulating symmetric division (proliferation) over asymmetric division (differentiation). In proliferation, one stem cell divides into two stem cells, while in differentiation, one stem cell divides into a stem cell and a somatic cell. Stem cell division is generally heavily weighted to differentiation, but it is possible to bias it the other way via mitochondria.
Mitochondria are relics of ancient bacteria taken up by early nucleated cells. These bacteria ultimately lost most of their own genes to their hosts and became endosymbionts. The typical human cell might contain a thousand of these, each with one or more small loops of bacterial-style DNA that code for enzymes. These enzymes run the citric acid cycle whereby glucose is burned to make ATP, the energy currency of the cell. Mitochondria are also employed to control stem cell fate by way of two switches. The first switch is mitochondrial morphology, which varies from point-like spheres (fission) to long rods or threads (fusion). In the mitochondrial fission state, SCs tend to differentiate, while in the fusion state, they tend to proliferate. The second switch is ATP production. Stem cells are normally quiescent with their mitochondria producing little or no ATP. Quiescence is maintained by mitochondrial pores (UCP2) that short circuit the citric acid cycle. By blocking those pores, ATP production can be restored, and if mitochondria are in the fusion state when ATP production begins, proliferation occurs.
Thus with stem cell niches filled, senolytic treatments become far more productive and epigenetic age can be rapidly reduced. My own epigenetic age has reversed 20 years in 3 chronological years, and I feel and look that much younger.
More to come
Iíve filed for patents on this process, and will be adding details of the process in the coming months.
© 2021 Lou Dischler