Poster Presenter

Problems Of Aging, Cancer And Evolution Are Solved: Key Role Of Deformation Stiffening Of Biological Structures
Valery P. Kisel
Russia

May be, the cause [of cancer] is the only one and simple, and we think too complicated, that’s why we could not answer this question. Loren Schwarz (Paris)
During the last three decades the old paradigm of the somatic mutation theory of cancer dictated the particular emphasis on the extremely complicated localized molecular and biochemical causes of the diseases. But the absolute new approach to transformations in biological tissues, BT, or physical phase transitions, allows us to understand the origin and the general features of aging and diseases from the physics of integral deformation at phase interfaces (conformations of molecular structures -DNA, RNA, etc., nucleation, growth, proliferation and aging (stiffening) of cells and their organelles, origin and development of endogenous chronic diseases, selection and evolution of species/populations) and to find the special physical-chemical methods of BT softening (new medical treatment of aging, diseases, living nature and men, aggression between people, nations and civilizations) [1,2].

The new approach to controlling role of cell interactions at their interfaces during growth (due to DNA activation, stresses between the old and new-born molecules, cells and their organelles) is confirmed with the next observation: robust cells may become cancerous only after neighboring tissues, rather than the cells themselves, have been exposed to carcinogens - the smallest deformable nuclei or “quantums” of BT deformation. Conversely, chemically treated epithelial cells grew into apparently normal mammary gland ducts when injected into healthy stromal tissue [2].

The experiments showed in vitro that the old (hard) human fibroblast interfaces stimulated proliferation of pre-malignant and cancer epithelial cells, which are able to make tumors at their entwinement to bare mice [2]. This increases the mismatch stresses at the interfaces of hard cells/pre-cancer cells thus intensifying the well-known high proliferation rate for cancer cells. At young (soft interfaces and the adjacent part of the intracellular liquids) fibroblast grafting this ability is less expressed thus again evidences for the key role of interface stresses in cancer. The fatigue deformation processes under body metabolism and physiological stress deformation in BT determine these transformations at interfaces and gradual interface stiffening (aging) (DSA) despite its weak softening (DS) [1].

Various experiments have shown that the exponential growth of relative size of eight types of entwined malignant tumors in mice as a function of the doubling number n of transformed cells is accompanied by the unified bell-shaped concentration dependence of reactive oxygen species, ROS, in cancerous cells in parallel with their maximum growth rate and ROS maximum at n_o = 5.6+/- 0.29 of the doubling cell number n (the stiffening of cells), then it drops abruptly to the concentration values of immature and embryonic cells (the softening of cells) [3]. In terms of deformation approach to phase transitions at phase interfaces this non-monotonous change in concentration of broken bonds-point defects is the independent and undisputable support of the gradual rise of DSA under tumor growth up to the moderate values of stiffening at no (the safe state for life) and then the DS of cancerous BT up to the dragless cell proliferation and growth at ultrahigh interface stiffening (final state for BT) as in “superconducting or superfluid solid” [4]. This is confirmed independently by numerous experimental facts that the initial cancerous tissues are something harder (due to interfaces and their intracellular liquids) than in the robust ones. And the cell stiffness (the Young’s modulus E) of developed cancer cells is more than 70% softer than in the healthy cells [5] like it is for the comparison of E in normal and superconducting metals [6]. So, the extra-hardening of cell interfaces and their adjacent intracellular liquids in cancerous cells play the same role in their proliferation as the lattice super-hardening for charge particles at superconductivity or liquids hardening at superfluidity [4].

The metabolism (mainly the electron fatigue deformation of cells) in the electron-transport-chains of mitochondria is determined by the direct DSA and the reverse DS flow of electric currents. The DS determines deformation durability of crystals and the longevity of BT due to the mechanical Bauschinger effect [4]. The data of recent works strictly confirms this in BT by the facts that the less life span of 12 species (birds and mammals) is, the more the rate of H₂O₂-active oxidizing defects nucleation at the reverse electron transfer in mitochondria of cardiomyocytes. This means that it is the lower reverse DS that makes lower concentration of H2O2 defects and the higher longevity of BC, and this is supported by the absence of higher life span at the direct electron transfer (the direct DSA of the Bauschinger effect). This is in line with the fatigue data on superconducting and normal metals.

The heavy cancer therapy is based on severe methods of tumor destruction (irradiation, physical-chemical effects, cell apoptosis stimulations, surgery, etc.) and softening (hyperthermia, physical-chemical treatment) [1]. But the active physical treatments like the well-known numerous methods of destroying superconductivity or superfluidity – the local acoustical and static deformation, the effect of non-thermal electromagnetic, high static electrical or magnetic fields, temperature, pressure, irradiation, chemical, physical and physiological fractionated stressing and starvation treatments (activation of anti-stress therapy [1,2]) of tumors with the proper amplitudes and frequencies, etc. – and with combination of faint methods concerned with DS of BT under increase of body adaptation, DNA and molecular transformations, low-dose fitotherapy, homeopathy, regional hyperthermia (40-43 ^oC), etc.) [1,2] must bring more effective forms of anti-cancer therapy.

1. V.P. Kisel, N.S. Kissel, in Functional Foods for Chronic Diseases. The microdeforma- tion of molecular and cell structures as a general mechanism of stress and adaptation.
New challenge to endogenous diseases, aging, and evolution. Part II. Activation therapy against chronic diseases. D.M. Martirosyan (Ed.) (D&A Inc., Richardson, TX, USA, 2006), 213-234.
2. Kisel V. P., Martirosyan D. M., in Functional foods for chronic diseases. Fatigue hardening is the key mechanism of aging and diseases. D.M. Martirosyan (Ed.), v. 3, (D&A Inc., Richardson, TX, USA, 2008) 84 –94.
3. Emanuel. N.M.. Doklady AN SSSR, 217, 245 (1974).
4. Kisel V. P., arXiv.org/abs/0905.4428v1 (2009).
5. Cross S.E., Jin Y.-S., Rao J., Gimzewski J.K. Nanomechanical analysis of cells from cancer patients. Nature Nanotechnology. 2007, v. 2, No 12, 780-783.
6. Kuz’menko I.N., Pustovalov V.V. Scripta Metall. 1985, v. 19, No 6, 685-688.