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Longevity Mitochondria


20 years, 10 months ago

11227  0
Posted on Jan 31, 2003, 11 a.m. By Bill Freeman

Purpose:  Exploration of phospholipid balance, genetic expression, impact of toxicity and longevity through examination of fatty acid imbalances revealed through red cell lipid biopsy from Johns Hopkins with definitive medical approaches towards metabolic stability of lipid metabolism and longevity.

Exploration of phospholipid balance, genetic expression, impact of toxicity and longevity through examination of fatty acid imbalances revealed through red cell lipid biopsy from Johns Hopkins with definitive medical approaches towards metabolic stability of lipid metabolism and longevity.





Characteristic findings in aging as the accumulation of very long chain fatty acids (VLCFAs) in states of toxicity, omega 3 and omega 6 imbalance/ deficiency, disturbed prostaglandin synthesis, overexpression of PLA2, poor cellular integrity and aberrant lipid production may be managed by opening a gateway into cellular metabolism with metabolic intervention (cofactors, substrates) through manipulation of cell membrane lipids and thereby impacting the systemic nature of the aging process.

Assessing the stability of the cell membrane through the examination of red cell lipids leads the clinician into a wide realm of metabolic strategies to influence the health of patient longevity. Lipids evolve into hormones, the bilipid layer of every cell in the body, prostaglandins, immune components, and myelin....  There is virtually no system of the body that does not require attenuation of specific fatty acid substrates and coenzymes to maintain health and repair of bodily tissues. The human cell membrane cannot be created nor its function controlled without respect to lipid substrate, yet fatty acid metabolism has been poorly delineated and often simply ignored in treatment protocols. Exploration of lipid metabolism brings a striking new tool that unlocks some of the complexities of longevity as lipid imbalance and deficiency have an intimate link to the endocrine, hepatic, renal, CNS, gastrointestinal, pulmonary, musculoskeletal and cardiovascular systems as well as exquisite capacity to impact aging.

The membrane of every cell and organelle is a lipid envelope that encases and protects the internal working cellular components. The bilipid layer is far more than isolation and protection, for linked and interlocked within the membrane are literally thousands of proteins (peptides) large and small that form the windows and doors of the cell. These mucopolypeptides form the gates for ingress and egress but also provide the multitudinous array of receptors that trigger not only access but create the vast intercellular communication and information system through their prostaglandin regulatory activity. Prostaglandins may have evolved to be the basic control mechanism that permitted metazoa agglomeration (which is principally what we are, a vast agglomeration of cells) since emerging from the primordial sea millions of years ago. Thus the mere thought of multicellular activity, and especially the evolution of humankind is, at our present level of knowledge, not possible without essential fatty acids, which are the precursors to the regulatory prostaglandins, which provide the communication and control absolutely necessary for a group of cells to stay together. Before one can advance beyond unizoa or single cell organisms into multi-cell metazoa there must be both  communication and eventually a means of regulation. This is the marvelous, magical world of the prostaglandins (PGs), the “local hormones” that control all cell to cell interactions without which there is no complex life form.

The explosion of fatty acid studies appearing in medical research have led us into a new era in our approach to resolving disease and the aging process, however, the focus of medical lipid manipulation has led to a great deal of confusion as pharmaceutical companies often dictate individual fatty acids as drugs rather than essential nutrients. As we begin to unfold the incredible complexity of lipid metabolism in the body human we are forced to acknowledge that lipid individuality must be respected if we are to achieve positive patient outcomes as we approach the process of longevity.

Lipids vibrate in the cell at millions of times/second. The double bonds of the omega 6 and omega 3 lipids are the singing backbone of life expressed through their high energy level. These bonds are  their vibratory song, and they absolutely carry a tune befitting every act and function in the exercise of life, providing all 70 trillion of our cells their flexible nature.  When renegade fats are over represented in the cell membrane they result in off key expression, and if strong enough, may spell cellular death and apoptosis. Healing the outer leaflet of the membrane, comprised primarily of phosphatidylcholine,  with phospholipid therapy, is our highest priority in addressing chronic illness and aging.
The cellular impact of aging and toxic burden results in disturbed prostaglandin synthesis, poor cellular integrity, decreased GSH levels, significant suppression of omega 6 arachidonic acid, imbalance of EFAs, marked elevation of Renegade fats and ultimately with demyelination (depressed DMAs). The presence of VLCFAs (very long chain fatty acids) are evidence of peroxisomal dysfunction and suppression of the beta oxidation of lipids and cellular respiration. Renegade fats (VLCFAs, Odd Chains, Branched Chains) are represented as an increase in fat content in the brain as discovered in stroke patients examined by Stanley Rapoport, Chief of the  Laboratory of Neuroscience at the NIH. Biotoxins and heavy metals are lipid soluble thus the effect upon cellular processes and hepatobiliary function is often gravely deranged. Often in the aging process patients do not possess a gross burden of toxins but rather a burden that has a finite impact upon the cell by blocking receptor sites such as G proteins, which act as a relay system through the cell.

Renegade fats such as very long chain fatty acids (VLCFA) that are over expressed, disrupt the membrane structure. There is a beautiful geometry to the membrane that is highly sensitive to the size of the lipid chains. The overall width of the fatty acid portion of the membrane is ~3 ½ nm which must be maintained for stability. Saturated or monounsaturated fatty acids with a length of 16 or 18 carbons are preferred to permit the structure to maintain optimal horizontal fluidity.  VLCSFAs that range from 20 to 26 carbons force the parallel dimensions vertically. There simply is not enough room. The distortion weakens the phosphate bonds that derive their strong attraction only as long as the phospholipids are parallel to each other on both sides of the membrane. The cell weakness is then expressed in leaky attraction to ion channels and receptors which marginalize cell cytosol fluids and electrolytes with the only option as early cell death.

In states of  aging it is paramount to stabilize omega 6 fatty acids and the lead eicosanoid Arachidonic acid before introducing omega 3 lipids. The manipulation of lipid distortion involves two basic essential fats: omega 6 and omega 3. There exists a crucial balance between omega 6 and omega 3 fatty acids in human lipid metabolism which has only recently been brought into clearer focus through the work of  Yehuda (1998). His development of the SR-3 (specific ratio of omega 6 to omega 3) has revealed that  the optimum ratio of omega 6 to omega 3 FAs is 4:1. AA, the lead eicosanoid, must be stable first along with the other w6 EFAs before w3 fatty acids are introduced and balanced. Clinicians are often met with poor patient outcomes when merely administering omega 3 lipids without first introducing omega 6 fatty acids, stabilizing the structural lipids, increasing the fat content of the diet, stimulating the ß-oxidation of renegade fatty acids, flushing of the gall bladder/biliary tree and supporting digestion of fats with bile salts and lipase. 

The body loses its ability to metabolize fats in states of toxicity and therefore becomes depleted in the eicosanoids and prostaglandins. Essential fatty acids are the precursors to the regulatory prostaglandins which are "local hormones"  providing the communication controlling all cell to cell interactions. The human cell membrane cannot be supported nor its function controlled without respect to lipid substrate, yet fatty acid metabolism has been poorly delineated in the medical literature. An optimum balance of fatty acids make up the dynamic membrane. The membrane of every living cell and organelle is composed of two fatty acid tails facing each other. This bilipid layer is so minute (3 nanometers) that it would take 10,000 membranes layered on top of each other to make up the thickness of this paper.  Yet the dynamics that occur within this tiny envelope with organelles prancing up and down the cytoskeleton microtubules is a microcosm that is a challenge for the human mind to envision.  All cells must synthesize molecules and expel waste. All cells must create, through gene expression, the proteins needed for cellular gates embedded in the membrane as ion channels and receptors. The ultimate control of how those peptides behave rests with the character of the membrane while  the  integrity  of  the membrane rests with the structural (oleic, stearic, palmitic, cholesterol) and essential lipids (omega 6, omega 3). Without control of membrane function  through  lipid  manipulation, the process of longevity and detoxication  is  compromised.  In essence,  the life of  the  cell  is  intimately  tied  to  membrane  health  and  the  health  of  the  entire organism. 

Our clinical protocol for longevity at the WellSpring Clinic in Wayne, PA is to initiate treatment with changing the patients’ overall diet, addressing the lipid balance and especially the outer lipid leaflet of the cell membrane through fatty acid therapy and the addition of supplementation targeted towards dissolving fibrin, clearing the liver/biliary tree, and healing the cell membrane.

Blood thinning agents such as Heparin and Warfarin increase blood flow around the blocked endothelium, however, reconstituting membrane fluidity can directly address coagulation in a natural restorative way.  Vibrant healthy membranes  will not permit agglomeration. The high polyunsaturated lipids with a preponderance of  phosphatidylcholine on the plasmic surface precludes undesirable clumping to occur. Treatment modalities should address dissolving fibrin and healing the cell membrane. By stabilizing lipid status with intravenous Phospholipid exchange and oral EFA supplementation we have  remarkable tools to unload the body burden of neurotoxins in both pediatric and adult populations, without side effects. Oral use of phospholipids  is also an effective intervention in addressing the aging process.

Through  isolating individual fatty acids and dimethyl acetyls in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, and the intricate circuitry of the prostaglandins.  The systemic health of the individual patient may be reached and targeted nourishment utilized through evidence based intervention which may yield positive patient outcome. Healing the membrane is virtually…. Healing the brain.

Phospholipids, cholesterol, cerebrosides, gangliosides and sulfatides are the lipids most predominant in the brain residing within the architectural bilayers. The phospholipids and their essential fatty acid components provide second messengers and signal mediators. In essence, phospholipids and their essential fatty acid components play a vital role in the cell signaling systems in the neuron. The functional behavior of neuronal membranes largely depends upon the ways in which individual phospholipids are aligned, interspersed with cholesterol, and associated with proteins. All neurotransmitters are wrapped up in phospholipid vesicles. The release and uptake of the neurotransmitters depends upon the realignment of the phospholipid molecules.  The nature of the phospholipid is a factor in determining how much neurotransmitter or metal ion will pass out of a vesicle or be taken back in. Phospholipid re-modeling may be accomplished by supplying generous amounts of balanced lipids and catalysts via nutritional intervention and the use of intravenous Phospholipid Exchange.

Newly documented research delineates how targeted lipid manipulation can dramatically influence the body human. Medicine has been slow to recognize lipid requirements to address neurological degeneration often accompanying states of aging. Data is now emerging from the medical literature but it must organized into meaningful therapeutic applications for use in a  clinical setting. By organizing the research data and isolating individual fatty acids in red cells we can now examine the cellular integrity/structure, fluidity, the formation of renegade fats that impair membrane function, myelination status, PLA2 status and the intricate circuitry of the prostaglandins and for the first time lipid treatment protocols may be established due to a clearer view into red cell membrane dynamics.

Examination of red cell lipids in patients age 50 with endocrine imbalance, immune dysfunction, hepatic involvement, Alzheimers, Post Stroke, Cardiovascular disease, ALS, cognitive impairment, Parkinson’s Disease, Glaucoma, Cataracts, gastrointestinal difficulties, hypercoagulation, CFS, MS, Depression, states of toxicity, CNS degeneration… reveal characteristic patterns that may be addressed with targeted lipid manipulation, stabilization of the membrane traffic through electrolytes, catalysts, medical foods, and  metabolic nutritional therapy. Medical data gleaned from the in depth analysis of red cell lipid biopsy via 10,000 analyses in our database is directly applicable to longevity protocols.

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