The test tube of dirt in question was filled by McGill University professor, Stanley Skoryna who during a four-month expedition with a team of 38 scientists journeyed to Easter Island to study the people, flora and fauna while they remained in their pristine untouched state before an airport was to be constructed on the remote island. The dirt revealed later under intense investigation at the Montreal Ayerst Laboratories to contain a bacterium Streptomyces hygrosopicus, that produced a defensive chemical with an amazing property. The ability to prolong life in diverse species. The chemical’s name is rapamycin, which acts as a fungal inhibitor. Easter Island is known locally as Rapa Nui, hence the name derivative.
Researchers had been finding antibiotics in finger pinches of dirt since the 1940’s. Isn’t it amazing that the Nobel Prize was given to Ernest Born Chain, Sir Walter Howard Florey with Sir Alexander Fleming in 1945 for discovering penicillin with its curative effects on infections, yet Nature had developed its own antibiotics at the dawn of time in Earth’s evolutionary past over a billion years ago? The Ayerst researchers had originally hoped to use rapamycin to treat yeast infections. ‘Biologists found rapamycin’s ability to depress proliferation of both yeast and human cells highly intriguing-it suggested that the compound suppresses the actions of a growth-regulating gene conserved across the billion years of evolution between yeast and people.’ according to the latest Scientific American January 2012 article A NEW PATH TO LONGEVITY written by David Stipp. Scientists had explored rapamycin’s ability to hinder proliferation of immune cells, using cell culture studies. Development now shifted away from yeast infection into high gear toward preventing immune rejection of transplanted organs. Rapamycin received U.S. Food and Drug Administration approval for patients who had received kidney transplants in 1999. During earlier explorations during the 1980s, researchers also learned that rapamycin acting as a drug, inhibits tumor growth. Current treatments for cancer in the form of two derivatives of rapamycin-Pfizer’s temsirolimus and Novartis’s –everolimus were approved for treatment in 2007.
Here in the article is the critical sentence from a shape tensegrity point of view: ‘Cells grow, expanding in size, when they are preparing to divide and proliferate.’ Yet no special emphasis in the article is mentioned, the cells change shape-that is the tipping point as far as tensegrity is concerned, that’s how tensegrity talks but like all conversations, you have to pay attention!
Michael N. Hall in 1999 with his colleagues at the University of Basel, Switzerland, identified the billion year old ancient target by discovering that rapamycin inhibits the effects of two growth-governing genes, which they called TOR1 and TOR2. The list of species known to posses TOR genes that govern cell growth (cell expansion-shape/tensegrity change) within mammals includes worms, insects and plants.
The 1990s were active years for researchers learning about TOR abilities, involving the gene’s roles in cells and the body as a whole, including a bearing on aging. These researchers found, ‘that the gene encodes a specific enzyme, performing as a catalytic protein, that combines in the cytoplasm with several other proteins to form a complex, called TORC1, which supervises a whole slew of growth-related activities in cells. Rapamycin mainly affects TORC1. ‘
TOR is also a nutrient sensor. Do you recall how strong the suppression of food and water on triggering seizures is? Seizures are stopped completely, remember this reference is biblical, it’s known in the Bible as the dropsy disease. So now to jump off that observation here’s TOR acting as a nutrient sensor, so the question becomes: what happens when nutrients are reduced i.e. anorexia??
The research teams discovered when food is abundant, TOR activity rises, prompting cells to increase their overall production of proteins and to divide. ‘ When TOR activity decreases, food is scarce, with a reduction in overall protein manufacture and cell division conserves resources. Now another process ‘amps up, called autophagy. Cells break down begin to break down defective components such as misshapen proteins and dysfunctional mitochondria, (the cells powerhouses), generating by-products that can be exploited as fuel or building materials.) OK let’s take a pause: if this autophagy process involves the use of misshapen proteins, it’s due to their shape being incorrect, I believe that is a logical tensegrity comment to make, but Nature uses these misshapen proteins, so somehow it’s like a reference template is used somewhere as an app 3D comparison. You know in NASCAR they have these wood profiles that the race stewards slide onto the race-car profile shape to make sure there is no change of the body shape, to check against uncovering better aerodynamics that cheater teams may attempt to make their race car faster, is that what is going on here, is it a Nature template 3D comparison process??
Before newborn mice start nursing they rely on autophagy to supply energy. When nursing starts, the pivoting point of TOR with autophagy swings back, TOR activity rises and autophagy slows. Such pivoting behavior appears to be the pivoting of sympathetic/parasympathetic which I have described in earlier blogs. That ‘s where calorie restriction slides into the problem, the interaction with the pivoting point. Mikespeak: Forgive me if I am not crystal clear as I write these thoughts are coming to me first hand, so I hope you appreciate the descriptions, my exuberance -this is what I try to do on a daily basis. I sit here like a painter with the sweep of the brush just leaving my hand creating a new image, I’m not sure what the final outcome will be but it’s the process that makes me feel so alive. Let’s back to TOR.
‘Researchers also discovered that signalling pathways headed by TOR and insulin in animals are intertwined: signaling pathways are (timed) sequences of molecular interactions that control a cell’s activities. Insulin is one of the nutrient sensors as a hormone released by the pancreas after meals to signal muscle cells and other cells to absorb glucose from the blood for energy.’ But insulin wears another hat too, insulin is also a growth factor. Both insulin with the help of related proteins help to ‘rev up’ the TOR pathway, a behavior that helps induce cells through out the body to grow and proliferate in response to nutrient intake. The pivot point of TOR at health with insulin involves a negative feedback loop: ‘stimulating TOR makes cells less sensitive to insulin’s signals. The dilemma of our current overweight society is, ‘chronic overeating, will activate TOR excessively to make cells increasingly unpivotable in terms of loosing their balance sensitivity to insulin. This stagnation of motion, termed, “resistance,” which tips over leading to high blood sugar levels which encompass diabetes then dragging other age related disorders like deteriorating heart problems.
TOR which appears at the pivoting point, also reacts to other stresses other than nutrient shortages, including low oxygen levels and DNA damage. TOR activity decreases when cells sense threats to survival, so could this be the basis of shape sensing at the core of survival. Could it be that as cells shape sense deterioration around themselves, like lack of oxygen for example, which means less pressure, which will influence the compressed tension/tensegrity within and around cells, since all cells are attached to one another. As if like a general retreat, a deterioration signal is sounded, the consequences result into a slowing of protein production with cell proliferation which will free up precious resources, so that cells can now preserve their integrity, enhancing their survival prospects, channeling their activity into DNA repair with other defensive behavior responses. Fruit flies even retreat in this fashion, as protein synthesis output gets curtailed protein production tips toward selective production of key mitochondrial components, as if the cells were recharging, in a sense rejuvenating themselves. A necessary cell survival sensor appears to be at the core of TOR sensing capacity, dare I say shape sensing capacity? As cells evolved under very harsh Earth condition niches in the geographical turmoil of early life coping also created their vulnerability, in effect hardening them by limiting their response under continuous ravages over time.
‘Nutrient starved cells curtail growth by reducing TOR activity.’ Let me translate this into tensegrity language: cells that are nutrient starved lose shape hence lose tensegrity compression/tension within their mesh-link of signalling, they suffer a general compression involving shape distortion. Part of the shape sensing mesh-link response is handled through the TOR activity reduction when this distortion occurs across the mesh-link apparatus. The shape sensing has to be happening somewhere, it isn’t just about shape, it’s about the genes linked to shape change output. That’s where TOR speaks to me in tensegrity language.
Clive McCay a Cornell University nutritionist demonstrated that putting young rats on near-starvation diets made them slow growing and extraordinarily long lived. Calorie restriction has been shown to extend maximum life span in species ranging from yeast to dogs, with preliminary evidence implying monkeys too. As I have mentioned in previous blogs starvation suppresses seizures. So these starvation effects within the brain are simply impressive, huge in fact in terms of metabolic effects. Which is exactly their associated relevance demonstrated in recent Ketogenic Diet (KD) experiments, here’s the authors conclusions: ‘In summary, this study demonstrates that KD inhibits mTOR pathway signaling in the brain and liver of healthy rats, and prevents late hippocampal mTOR activation after KA-induced SE(status epilepticus). This mTOR inhibition may underlie some of the physiologic effects of KD, including growth impairment, anticonvulsant actions, and potential antiepileptogenic effects. Further studies are necessary to prove a causal relationship between mTOR inhibition and antiepileptogenic actions of the KD.’ cited from The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway Sharon S. McDaniel, Nicholas R. Rensing, Liu Lin Thio, Kelvin A. Yamada, and Michael Wong Epilepsia 52(3):e7–e11, 2011
‘By the early 200s researchers knew enough about TOR’s functions to suspect that blocking its influence in cells might mimic caloric restriction,’ which was reported in the cited Epilepsia paper above, testing mice with the ketogenic diet. ‘In 2003 Tibor Vellai, a Hungarian researcher visiting at the University of Friebourg in Switzerland, led a round-worm study offering the first evidence that inhibiting TOR may oppose aging: his experimental manipulations involved genetically suppressing TOR synthesis in worms, his colleague team doubled the worms’ average life span.’ Similar findings in a variety of other species including fruit flies, yeast cells confirmed this increased longevity of Vellai, but also inhibited mutant genes already known to extend life span. Experiments involving roundworms performed about a decade earlier whose mean and maximum life spans were doubled by mutations which were later shown to interrupt their species’ particular method of insulin signalling. The discovery that aging could be dramatically slowed by altering a single gene pointed to human aging might be retarded with drugs. ‘
If you Google Michael N Hall and TOR one of the citations found is an essay entitled : TOR SIGNALLING: FROM BENCH TO BEDSIDE written by Michael N. Hall. The report is highly detailed but the essence for me is striking. Here are some of the observations in Michael Halls own words. ” The TOR signaling pathway appears to be a primordial pathway that has been conserved throughout eukaryotic evolution to control the fundamental process of cell growth.” Here’s another tensegrity talk statement, ” The TOR-2-unique branch so far contains a single effector pathway that controls the polarized organization of the actin cytoskeleton. We view this branch as mediating the spatial control of cell growth.” The next statement is my favorite, ” Schreiber and colleagues have referred to TOR as a multichannel processor ( Shamjii et al, 2000)” So not only does TOR sense nutrients it links into the cytoskeleton, in other words the cells together in their architecture of form sense the availability or deprivation of nutrients by the shape of their form, which is what I have called shape sensing. mTOR also integrates nutrient and insulin signals to control cell growth with an interactor called raptor, also linking with scaffold proteins, that act as amino acid sensors. So where ever you look in cells, there are all these multichannel processor TOR links into the cytoskeleton So what is the conclusion? The cell’s shape senses itself, it’s tensegrity based shape sensing.