The Streaming Organism

Also see:
Gershom Zajicek’s Website
Diabetes: Conversion of Alpha-cells into Beta-cells
Research by Zajicek, et al. on Pubmed
Nutrition and Brain Growth in Chick Embryos
The Brain – Estrogen’s Harm and Progesterone’s Protection

Quotes by Ray Peat, PhD:
“Even the liver and adrenal gland are now known to be continuously renewed by “cell streaming,” though at a slower rate than the skin, conjunctiva, and intestine.”

“Choosing the right foods, the right atmosphere, the right mental and physical activities, and finding the optimal rhythms of light, darkness, and activity, can begin to alter the streaming renewal of cells in all the organs. Designing a more perfect environment is going to be much simpler than the schemes of the genetic engineers.”

“For almost the entire 20th century, the medical experts completely ignored the work of experimenters such as Polezhaev, and their excuse was that when a brain was sliced, dividing cells were never seen, and they could be seen in the skin and liver, which they knew could regenerate. The reason, for which the absence of evidence was the excuse, for denying regeneration in the heart and brain was that they were committed to the world-view of August Weismann. Since the brain isn’t in a chemically exposed situation, such as the skin, gut, and liver, there’s no need for it to make new cells every day. Polezhaev showed that a degenerating brain cell was the stimulus for producing a new cell. In the absence of evidence showing that medical education is radically less stupid than previously, I will ignore their present doctrines, as I ignored their previous opinions.”

“Partly, it’s that the environmental conditions that advance puberty also inhibit brain development, namely, the low CO2/O2 ratio and high PUFA environments. But estrogen’s effect, increasing the average amount of free fatty acids in the circulation, works with the bad environment. With a different environment, estrogen’s function would probably include increasing brain plasticity.”

Med Hypotheses. 1981 Oct;7(10):1241-51.
The histogenesis of glandular neoplasia.
Zajicek G.
Tissues in the organism may be divided according to their proliferative capacities into three categories: 1. Fast replicators (FR) e.g., epidermis; 2. Slow replicators (SR) e.g., liver and 3. Non replicators (NR) e.g., nerve cells. Evidence is presented that FR as well as SR tissues continuously proliferate exhibiting two distinct histomorphological structures; a progenitor region in which cells are formed and a functional region into which they enter. Throughout their displacement, the cells cover a typical path denominated as tissue radius. The SR tissues e.g., parotid gland, mammary gland, liver and prostate, exhibit similar ontogenies, and proceed during regeneration and neoplasia through similar stages. All are compound glands with two distinct stem cell types, one residing in the excretory duct epithelium and the second in the intercalated duct. Each stem cell gives rise to its typical neoplasm. Excretory duct originating neoplasms consist of papillomas, epidermal and adenocarcinomas, while intercalated stem cell bound neoplasms embrace the canalicular adenoma, oncocytoma acinic cell and lobular carcinomata. All tissues continuously stream along the tissue radius. Evidence is presented that even the liver cords are continuously displaced from the limiting lamina toward the terminal hepatic (or central) vein. The histological image of these tissues actually reflects an instantaneous picture of cells in a continuous flux.

Brain Neurogensis:
J Cereb Blood Flow Metab. 2007 Aug;27(8):1417-30. Epub 2007 Mar 28.
Regeneration and plasticity in the brain and spinal cord.
Johansson BB.
The concept of brain plasticity covers all the mechanisms involved in the capacity of the brain to adjust and remodel itself in response to environmental requirements, experience, skill acquisition, and new challenges including brain lesions. Advances in neuroimaging and neurophysiologic techniques have increased our knowledge of task-related changes in cortical representation areas in the intact and injured human brain. The recognition that neuronal progenitor cells proliferate and differentiate in the subventricular zone and dentate gyrus in the adult mammalian brain has raised the hope that regeneration may be possible after brain lesions. Regeneration will require that new cells differentiate, survive, and integrate into existing neural networks and that axons regenerate. To what extent this will be possible is difficult to predict. Current research explores the possibilities to modify endogenous neurogenesis and facilitate axonal regeneration using myelin inhibitory factors. After apoptotic damage in mice new cortical neurons can form long-distance connections. Progenitor cells from the subventricular zone migrate to cortical and subcortical regions after ischemic brain lesions, apparently directed by signals from the damaged region. Postmortem studies on human brains suggest that neurogenesis may be altered in degenerative diseases. Functional and anatomic data indicate that myelin inhibitory factors, cell implantation, and modification of extracellular matrix may be beneficial after spinal cord lesions. Neurophysiologic data demonstrating that new connections are functioning are needed to prove regeneration. Even if not achieving the goal, methods aimed at regeneration can be beneficial by enhancing plasticity in intact brain regions.

Science. 2003 Aug 8;301(5634):805-9.
Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants.
Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R.
Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

Liver. 1985 Dec;5(6):293-300.
The streaming liver.
Zajicek G, Oren R, Weinreb M Jr.
Twenty male adult rats weighing 200 g were injected with tritiated thymidine (3HTdR). The animals were then killed in groups of five, at the following times: 1 h, 1, 3 and 5 weeks. Autoradiograms of sections through the liver were prepared. The distances between labelled cells and the portal space rim were measured. One hour after labelling most labelled cells were confined to a region extending from the portal space rim up to a distance of 700 micron, which roughly corresponds to Rappaport’s hepatic acinus zones-1 and -2. Throughout the experiment lasting 5 weeks labelled cells entered zone-3 and advanced toward the terminal hepatic vein. Hepatocytes travelled at a daily velocity of 1.44 micron, covering daily 0.324% of the acinus diameter. During the experiment acinus size did not change appreciably. The estimated mean hepatocyte cell cycle time was 37 days and its life expectation, 201 days. These experiments show that the liver is essentially a slowly renewing cell population. Hepatocytes nascent at the portal space gradually stream toward the terminal hepatic vein where they are probably eliminated by apoptosis. Their journey lasts 201 days. Since hepatocytes are glued together with tight junctions, all have to advance toward their terminal hepatic veins en masse. During their voyage, they traverse the three acinus zones, and since in each they produce different enzymes, each zone represents a differentiation state of the advancing cell. It is suggested further that the streaming hepatocyte carries with it its nerve supply and is accompanied by sinusoidal endothelium and Kupffer cells.

Diabetes Res. 1990 Mar;13(3):121-5.
Streaming pancreas: islet cell kinetics.
Zajicek G, Arber N, Schwartz-Arad D, Ariel I.
Thirty male young adult rats aged 7 weeks, weighing 200 g, were injected with 0.5 microCi/g body weight tritiated thymidine (specific activity 5.0 Ci/mM). The rats were then killed in groups of five, at the following times: 1 hour, and 14, 28, 42, 56, 90, and 120 days. The pancreata were dissected, embedded in paraffin, and cut into 5 microns thick sections which were then dipped into liquid emulsion. The labelling index of acini and islet cells was estimated in each autoradiogram, and their distance from intercalated duct was measured. Acini and islet cells streamed away from the intercalated duct at a daily velocity of 0.52 microns. Acinus labelling index which was initially 0.78% declined with time. Islet cell labelling index was initially 0.38%. In the following days it climbed upward reaching on the 42nd day its peak value of 0.78%. From then onward it declined to a low of 0.38%. Since cells were labelled only once, and labelling was instantaneous, it is concluded that labelled acinus cells entered the islet, and that acinus cells are actually islet cell precursors. The pancreas is structured kinetically like other exocrine glands, being a two compartment cell renewal system which continuously renews its cells. The pancreocyte is a descendant of an intercalated duct progenitor. After leaving the duct it turns into an acinus cell, gradually approaching the Langerhans islet. After crossing its border it becomes an islet cell, and proceeds toward the islet center. Its population size dwindles exponentially until at islet center all cells are eliminated.

In the adrenal glands, renewing cells stream from the capsule on the surface of the gland toward the center of the gland. The first cells to be produced in a regenerating gland are those that produce aldosterone, the next in the stream are the cortisol producing cells, and the last to be formed are the cells that produce the sex hormones, the androgens including DHEA, and progesterone. In aging, after the age of thirty, the renewal slows, but the dissolution of the sex hormone zone continues, so the proportion shifts, increasing the ratio of aldosterone and cortisol producing cells to the layer that produces the protective androgens and progesterone (Parker, et al., 1997). -Ray Peat, PhD

Also see: Stress and Aging: The Glucocorticoid Cascade Hypothesis

J Endocrinol. 1986 Dec;111(3):477-82.
The streaming adrenal cortex: direct evidence of centripetal migration of adrenocytes by estimation of cell turnover rate.
Zajicek G, Ariel I, Arber N.
Thirty adult male rats were injected with 0.5 microCi [3H]thymidine/g body weight (specific activity 5 Ci/mmol) and killed, in groups of five, 1 h and 14, 30, 60, 90 and 120 days after injection. The displacement of labelled adrenocytes with time was estimated in autoradiograms of adrenal sections. The radial distance of the labelled cell from the capsule was measured with an eyepiece micrometer and expressed in cell location units, i.e. the number of cells separating the labelled cell from the capsule. One hour after labelling, 95% of labelled cells were confined to the outer quarter of the cortex. During the following days, adrenocytes were displaced inwardly, approaching the medulla at a velocity of 0.24 locations/day. They traversed the three cortex zones, reaching the medulla after 104 days. The three adrenal zones represent three differentiation states of the adrenocyte. When young, the adrenocyte secretes aldosterone, after leaving the glomerulosa it produces corticosteroids and on reaching the reticularis it produces sex hormones. The adrenal cortex is a cell renewal system made of two compartments. A progenitor compartment extending between locations 1 and 15, and a functional compartment, covering locations 16-64. The first compartment produces 0.47 cells daily, which enter the second. Half of them die on their way while the rest are eliminated in the reticular zone. The cell stream is nourished by a subcapsular stem cell.

J Clin Endocrinol Metab. 1997 Nov;82(11):3898-901.
Aging alters zonation in the adrenal cortex of men.
Parker CR Jr, Mixon RL, Brissie RM, Grizzle WE.
Whereas aging has been shown to be associated with striking reductions in circulating levels of adrenal androgens in humans, the alteration in adrenal function that occurs in aging has not been identified. We sought to determine if there are changes in the zonation of the adrenal in aging men by performing histomorphologic analyses of adrenal specimens that had been obtained at autopsy following sudden death due to trauma. We evaluated adrenals from 21 young men (20-29 yrs) and 12 older men (54-90 yrs); inclusion criteria required the presence of medullary tissue in the specimen and fixation within the first 24 hrs postmortem. Sections stained with H/E were examined microscopically and areas of the cortex that included adjacent medullary tissue were chosen for quantitative evaluation by use of a computerized image analysis system. The average width (arbitrary units, pixels) of the zona reticularis and that of the combined zonae fasciculata/glomerulosa were determined from sections stained for reticulum fibers. The zona reticularis represented 37.1 +/- 1.9% of the total cortical width in the young men, which was significantly greater than that of the older men (27.1 +/- 3.3%, P = 0.0082). The zona fasciculata/glomerulosa to zona reticularis ratio in the young men (1.84 +/- 0.15) was significantly less that that of the older men (3.29 +/- 0.47, P = 0.0011). There was no significant difference in the total width of the cortex in young compared to older men. These data suggest that aging results in alterations within the cortex of the adrenals in men such that there is a reduction in the size of the zona reticularis and a relative increase in the outer cortical zones. A reduced mass of the zona reticularis could be responsible for the diminished production of dehydroepiandrosterone and dehydroepiandrosterone sulfate that occurs during aging.

Gershom Zajicek and his colleagues have demonstrated an organized renewal of tissues, in which new cells are born with the division of stem cells, and “stream” away from their origin as they mature, and finally are shed or dissolved. A few studies have demonstrated a similar kind of migration of cells in the brain (Eriksson, et al., 1998; Gould, et al., 1999), a process which differs by the absence of systematic dissolution of mature brain cells. -Ray Peat, PhD

Nature Medicine 4, 1313 – 1317 (1998)
Neurogenesis in the adult human hippocampus
Peter S. Eriksson, Ekaterina Perfilieva, Thomas Björk-Eriksson, Ann-Marie Alborn, Claes Nordborg, Daniel A. Peterson & Fred H. Gage
The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.

Science. 1999 Oct 15;286(5439):548-52.
Neurogenesis in the neocortex of adult primates.
Gould E, Reeves AJ, Graziano MS, Gross CG.
In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.

Hair Regeneration:
Nature 447, 316-320 (17 May 2007) | doi:10.1038/nature05766; Received 30 August 2006; Accepted 20 March 2007
Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding
Mayumi Ito1, Zaixin Yang1, Thomas Andl1, Chunhua Cui1, Noori Kim1, Sarah E. Millar1 & George Cotsarelis1
The mammalian hair follicle is a complex ‘mini-organ’ thought to form only during development1; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits2, 3, mice4 and even humans fifty years ago5. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented6. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.