APOPTOSIS (CELL SUICIDE OR PROGRAMMED CELL DEATH)

Apoptosis determines if you are firm and fit or flabby and at risk. Stress levels trigger apoptosis and you can read how you are coping on your tongue.  Apoptosis is the most important new concept underpinning medical thinking.  We were all taught that cells simply die by necrosis.  With necrotic death, all of the cell’s innards are explosively released, creating painful inflammatory response.  Turns out, the body is far more sophisticated than that. 

Cells are programmed to quietly fade and/or die for a variety of reasons during growth and development as well as during wound repair.  Activated phagocytic cells, defective or infected cells also undergo this ‘altruistic’ programmed cell suicide called apoptosis.

Phagocytes are a class of cells which started in bone marrow as stem or dendritic cells, which also become fibroblasts, chondrocytes, chondroclasts, osteoblasts, osteoclasts, monocytes, macrophages, lymphocytes, neutrophils and polymorphonuclear cells. Loosely termed "white blood cells," phagocytes have the ability to ‘gobble’, engulf and ingest, and therefore destroy, foreign matter or organisms. This process is called phagocytosis. 

With apoptotic cell suicide, the cell’s useful organelles are prepackaged for efficient reuse and easier reclamation via phagocytosis by associated dendritic gobbler white blood cells, creating quiet well-organized reorganization of tissues for growth and repair.

The stress messaging of infectious agents (bacteria) prolongs the life of cells by delaying maturity, but apoptosis will eventually occur with all cells. A macrophage is one of the cells suffering the least apoptosis, typically accepted to have a 45 day life (plus or minus). By comparison, a neutrophil suffers apoptosis in 24 hours, and makes a very poor home for chronic intracellular pathogens (by comparison with the macrophages).  

Monocytes are highly versatile cells playing crucial roles in the maintenance of immune homeostasis. These cells are released into the bloodstream from the bone marrow and, in the absence of specific survival signals, are programmed to undergo apoptosis in 24–48 hours.  EBV infection of monocytes rescues them from undergoing spontaneous apoptosis and dramatically enhances their survival.  EBV infection also induces acute maturation of monocytes to long-lived macrophages with morphological and phenotypic characteristics of potent antigen presenting cells.

In the womb, developmental webs between human fingers quietly reorganize and disappear.  Orchestrated by associated phagocytic dendritic cells (gobbler cells), bone and gum cells disappear and mysteriously melt away to allow teeth to erupt. 

This same mechanism creates a pimple (an infectious skin opening) or allows a purulent fistulous tract to emerge from a sick tooth through bone.  Some folks have receding, thin and atrophic gums as well as bone.  Others have thick, vibrant even hypertrophic bone and gums.  Changes in apoptotic signaling to different categories of tissues determine these differences.

During development, parts of the brain must die to allow rewiring for speech.  Environmental toxins and excessive stress messaging from the civilized diet and electric light sometimes cancels apoptosis of brain nerve cells programmed to die as necessary pruning for brain development and reorganization.  This compromises speech development and other socially interactive skills.  Autistic children end up with larger differently-wired brains than normal children. 

Apoptosis signaling is naturally heightened by messenger RNA during rapid growth, especially around the inherently stressful peak 5-7 year growth spurt(s), and is at apogee during tooth shedding and eruption.  Appearance of ‘twelve year’ molars (second permanent molars) signal another apoptotic peak and the beginning of the next and biggest programmed stress in life, the pubertal growth spurt.

Growth spurts are well known to be the best time to move teeth orthodontically.   Very light consistent physiologic forces on teeth promote efficient apoptotic remodeling of bone with gentle movement of the teeth carrying and even generating bone.  Excessive forces transmitted through teeth creates focal necrosis, hastened painful inflammatory death of cells with delayed movement of teeth, even sometimes causing shortening of tooth roots and often resulting in less than optimal remodeling of bone.

Stress hormones cause most white blood cells to remain sequestered in liver, spleen and lymph nodes as well as reducing motility of circulating phagocytes.  This disables cellular immunity, allowing accumulation of unfavorable pathogenic biofilm on still porous teeth. 

Enamel and dentin are a permeable cover over our outer cellular barrier formed by dentinoblasts.  Extracellular fluid flows from the dentinoblast, through the dentinal tubules and through microscopic pores in enamel that allows the tooth to ‘sweat’ or be ‘flushed’ from the inside to the outside during anabolic tides. When stress hormones are triggered, this flow reverses, potentially drawing bacterial lipopolysaccharides from sticky strep mutans (which mimics our endotoxin) towards our internal cellular immune barrier.  This excites the auto-immune process of tooth decay.

Streptococcus mutans is a bacterium with a unique survival strategy of living where most bacteria do not like to live, in an acid environment.  Many sticky mutans varieties have lipopolysaccharide markers in their cell walls which mimic our endotoxin, with its highly virulent and threatening immune message.  These small antigenic molecules can be carried by extracellular fluid and drawn to the inner pulp through enamel pores during catabolic tidal flows, alarming the dentinoblasts, our outer cellular border.

 Dentinoblast produced cytokines call in phagocytic white blood cells.  These dendritic immune cells congregate under the dentinoblast border.  They create a ‘protective’ oxidative basic outflow aimed at the outer acidic irritant, often quickly dissolving the tooth from the inside out via the highly alkaline saponification and liquefaction necrosis of uncontrolled inflammation. 

Heightened apoptotic signaling that occurs during programmed rapid growth spurts promotes increased survival of inflammatory pulpal phagocytes along with easier apoptotic death of structural ‘bordering’ dentinoblasts allowing decay to quickly penetrate the dental pulp.

Heightened apoptotic signaling creates the highest rates in enamel decay classically seen at these peaks of growth.  Acne pimples are exfoliating cysts based on a similar signaling process and are also maximumally expressed when tooth decay crests during the pubertal growth spurt.

Enamel-like neuroectodermal cells guide mesodermal tooth root formation.  After root development of permanent teeth, these root-retained ectodermal enamel-derived epithelial cells of Hertwig are programmed to die.

Neural crest cells aiding and guiding root development may not die as programmed if their apoptotic signaling is cancelled due to stress messaging overwhelming abundance messaging at that critical developmental juncture.  They remain alive, dormant on the root surface.  Although some develop into calcified ectodermal enamel pearls. 

Enamel pearls or epithelial rests then become permanent internal antigenic markers waiting to become activated when humoral immunity becomes upregulated.  Patterns of antigenic enamel epithelial cells and pearls are formed on root surfaces during growth spurts of ages 4-10 (peaking at stress apogees of ages 5-7).  This predicts the clinical pattern of adult periodontal disease.   Systemic bone density diminishes and stress heightens directly during the shedding of the deciduous incisors and eruption of the six year molars.  

Inflammatory activation typically occurs later in life when cellular immunity becomes compromised and humoral immunity is reflexly upregulated, creating autoimmune periodontal destruction, with similar inflammatory cytokines to those expressed in rheumatoid arthritis.  When these autoimmune ‘lytic’ lesions break through into the mouth, they become infected with characteristic opportunistic oral bacteria. A pathogenic biofilm is encouraged due to local environmental conditions as well as depressed cellular immunity.

Cellular immunity eventually becomes disabled due to difficulty in recycling reduced glutathione. Glutathione lack is caused by excessive environmental load and/or genetic predisposition, poor waking and sleep cycles, negative emotions, weak breakfast (with too little sustaining protein, carbohydrate, water, fats or minerals), too much sugar or just too many calories all at once. 

Dental plaque accumulation is often the first clue to failed cellular immunity.  Excess mucus, sinusitis, hay fever, hives, allergies, hypersensitivities and autoimmune disease signal the compensatory upregulation of humoral immunity, often accompanied by painful uncontrolled inflammation and autoimmune destruction.

Many female patients with periodontal diseases or TMJ symptoms also have endometriosis.  Endometriosis is set up by excessive stress messaging occurring during descent of the ovaries, leaving dormant glandular cells still-living along developmental tracts.  Fibroid activation occurs later in life when cellular immunity becomes compromised and humoral immunity is upregulated. 

In cycling females, if the egg is not fertilized, endometrial cells are programmed to apoptotically die every 28 days, quickly stopping the production of progesterone, triggering a timely three day menses.  If there are too many current ‘stress messages’, these tissues live on, disordering hormonal production, extending the menses and altering the monthly clock.

DNA is a stable scaffold of possibilities designed to interact with variable environments that creates species, but DNA has no enzyme activity of its own.  Molecules of RNA (as ribozymes) combine memory capacity with enzyme capability giving only ever-present and less stable RNA the ability to respond to the environment and create individuality.

 The RNA world is easy to ignore.  These more changeable single-stranded cousins of stable intertwined double-stranded DNA surround and envelop us in our awareness.  Ribozymes are bound to the endoplasmic reticulum as ribosomes but also swim freely in the cytoplasm and extracellular fluids, mostly ignored and appearing in the background everywhere in highly-magnified microscopic optical fields, much like dust particles dancing with Brownian movement in sunlit air. 

These always-present viroids, mystical molecules of the RNA world are our primary integrators with the environment and activators of gene expression.  RNA expresses itself through viroids, viruses, microscopic motors and enzymes, controlling our individual DNA and ultimately our actions as well as environmental and societal interactions.

 Since the beginning of time’s interaction with life there have been but two environments, abundance and its lack (or scarcity).  The RNA world existed before the DNA world and still exists, interpreting the environment and telling our DNA what to do. 

With RNA messaging from springtime abundance (richly found in sunshine, pigments in rapidly-growing leaves, soaked germinating seeds, nuts or grains, eggs and fermented products) the body’s structural tissues become anabolic, firm, resilient and resistant to disease.  The bear awakes from hibernation, flabby and out of shape, but gets firm and muscular in just a few weeks, with the foods and environmental messaging of springtime.

With significant RNA perceptions of lack of light, drought, stress and scarcity (from dehydrated, dried or toasted seeds, nuts or grains and even worse, weak or no breakfast) survival hibernation response is triggered and the body stops making muscle and stores fat, becoming isolationist, depressed, irritable, catabolic, flabby, weak and autoimmune.

When RNA perceived stress messaging becomes overwhelming, cell types are triaged into expendable (structural) and necessary (survival) categories.  Structural tissues (which also function as our reservoirs) are bone, teeth, skin and muscle.  Preservation or survival cells are fat cells, nerve cells, taste buds and inflammatory white blood cells (our functionally mobile neurons).

 When environmental stress messaging overwhelms abundance messaging to our genes, structural cells wane (are allowed to die early by apoptosis) and the body cancels cell suicide in its survival cells.  Paradoxically, already stressed or defective cells of the body (designed to eliminate themselves by undergoing apoptosis or cell suicide) also have that signal cancelled and live on to grow, potentially becoming cancerous tumors.

Smoking many cigarettes and drinking lots of coffee surprisingly delays onset of Parkinson’s disease (caused by toxin-induced apoptosis of substantia nigra brain cells).  Epidemiologically, AGEs (advanced glycation end-products) can explain what is called the ‘Parkinsonian paradox.’  Parkinson’s symptoms result from early cell death of these brain cells that primarily produce dopamine. 

Classic AGEs stressors are toasted and burnt sugars in tobacco, coffee, chips, fries and, whoops, boxed breakfast cereals (even organic) which hasten most inflammatory diseases.  Stress actually delays previous apoptotic signals induced by other toxicity in Parkinson’s disease, providing a salutary effect for about one person in a group of two hundred.  Most of us however, engender greater risk to diabetes, periodontal disease, heart disease, stroke and cancer with stressful behaviors.

  Excessive stress messaging comes from too little sleep, too little sunshine or weak breakfast; or from toxic synergy of heavy metals such as mercury, lead and arsenic; or the halides bromine, chlorine and fluorine; and virulent molds, resident yeasts, bacteria and viruses allowed due to compromised cellular immunity; vaporous organophosphates, phthalates, petrochemicals, solvents and addictively tasty browned or glycated sugar molecules, or even just eating too many foods containing glycoproteins that mimic an incompatible blood type.

 When daily anabolic repair tides are overwhelmed by catabolic flows, ensuing stress-responsive inflammatory chemistry allows ‘structural’ cells (like muscles, skin, bones, teeth as well as the ‘shag carpeting’ filiform papillae of the tongue) to fade and wane by undergoing apoptosis, programmed cell death.  Nerves and taste buds (containing nerves) survive. 

Eastern medicine teaches that the first sign of stress overwhelming repair is a red tip to the tongue.  The red tip then enlarges as waning atrophied filiform papillae create a smoother tongue with newly visible ‘strawberry spots,’ survival taste buds called fungiform papillae.

With overwhelming metabolic stress, apoptosis is shut down in ‘survival’ cells such as fat cells, creating growing expanding flab.  Stressed inflammatory ‘gobbler’ white blood cells also live on, dissolving bone and creating chronic autoimmune destruction and pain. 

When enough balancing messages of abundance from the environment are perceived by our dualistic steroid receptors, they modulate our nuclear DNA gene expression.  Now vigorous structural filiform papillae restore full pink shag carpeting to the tongue; the mouth stays free of pathogenic biofilm effortlessly; flab turns to firm; tumors shrink and defective cells quietly commit apoptotic cell suicide in a timely fashion.

 Messaging of abundance comes from the attitude of gratitude, sunshine, rhythm, effective sleep, sustaining breakfasts, soaked seeds, nuts and grains, raw or barely cooked eggs, vibrant vegetables, fresh pressed vegetable juices and fermented foods. 

The beneficent nuclear steroid receptor transmits invigorating mild hormetic stresses to the genes.  It also responds to fat-soluble vitamins A, D, Es, Ks, bile, steroid hormones, retinoids and other sun generated pigments, proanthocyanidins, resveratrol and the salvesterols, aromatic essential oils and foundationally, the omega-3 and omega-6  essential fatty acids.

Steven N. Green, DDS, 10261 SW 72 St., #106, Miami, FL 33173, 305-273-7779,

August 26, 2009, antiagingdentist.com, ddsgreen@bellsouth.net