Cofanie zegara biologicznego

Telomeraza - nadzieja na odmłodzenie

Podział komórki zaczyna się od replikacji DNA, czyli materiału genetycznego. Niestety polimeraza DNA, czyli enzym, który replikuje DNA, nie potrafi zacząć replikacji. Replikacja DNA rozpoczyna zatem polimeraza RNA, która rozpoczyna syntezę RNA na końcu łańcucha DNA. Na końcu łańcucha DNA znajduje się pewna ilość powtarzających się odcinków DNA zwanych telomerami. Po zsyntetyzowaniu RNA na telomerowej matrycy DNA może wkroczyć polimeraza DNA, która kontynuuje polimeryzację, ale już DNA, a użyty odcinek telomeru zostaje zdegradowany. W ten sposób, za każdym podziałem komórki i co za tym idzie, replikacji DNA, łańcuch DNA zostaje skrócony o jeden odcinek telomeru. Z procesu tego wynika, że dana komórka może się podzielić skończoną ilość razy, a co za tym idzie wszyscy jesteśmy zaprogramowani na śmierć. Brak możliwości podziału komórkowego prowadzi również, że pewne komórki nie mogą już być zastąpione innymi, co oznacza starzenie się. Proces ten, oczywiście może być przyspieszony lub opóźniony warunkami środowiskowymi, takimi jak dieta, czy ekspozycja na promieniowanie jonizujące, w tym słoneczne. Niemniej jednak, prędzej, czy później, zabraknie komórek macierzystych do odbudowy zniszczonych komórek. Stąd uwaga wielu naukowców zwróciła się w kierunku możliwości dobudowywania telomerów na końcach łańcucha DNA.

Telomery dobudowuje enzym zwany telomerazą, która, w normalnej sytuacji, pojawia się tylko podczas gametogenezy, czyli powstawania jaja i plemnika. Pojawienie się telomerazy w życiu dorosłym związane jest z powstawaniem komórek rakowych, które poprzez obecność telomerazy uzyskują nieśmiertelność.

Grupa badaczy z Kalifornii i Teksasu zaproponowała sposób, w którym dobudowywanie telomerów jest kontrolowane, to znaczy, że ilość dobudowanych telomerów, lub aktywność telomerazy ma charakter przejściowy, a więc nie powstaje komórka rakowa, ale komórka macierzysta, która może zastąpić inne zniszczone komórki. Jest to niewątpliwie duże osiągnięcie naukowe, które daje niejako możliwość odmładzania ludzi.

Poniżej podaję raporty z cytowanych badań.

FASEB J. 2015 Jan 22. pii: fj.14-259531. [Epub ahead of print]

Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.

Ramunas J¹, Yakubov E¹, Brady JJ¹, Corbel SY¹, Holbrook C¹, Brandt M¹, Stein J¹, Santiago JG¹, Cooke JP¹, Blau HM².

Telomere extension has been proposed as a means to improve cell culture and tissue engineering and to treat disease. However, telomere extension by nonviral, nonintegrating methods remains inefficient. Here we report that delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts increases telomerase activity transiently (24-48 h) and rapidly extends telomeres, after which telomeres resume shortening. Three successive transfections over a 4 d period extended telomeres up to 0.9 kb in a cell type-specific manner in fibroblasts and myoblasts and conferred an additional 28 ± 1.5 and 3.4 ± 0.4 population doublings (PD), respectively. Proliferative capacity increased in a dose-dependent manner. The second and third transfections had less effect on proliferative capacity than the first, revealing a refractory period. However, the refractory period was transient as a later fourth transfection increased fibroblast proliferative capacity by an additional 15.2 ± 1.1 PD, similar to the first transfection. Overall, these treatments led to an increase in absolute cell number of more than 10¹²-fold. Notably, unlike immortalized cells, all treated cell populations eventually stopped increasing in number and expressed senescence markers to the same extent as untreated cells. This rapid method of extending telomeres and increasing cell proliferative capacity without risk of insertional mutagenesis should have broad utility in disease modeling, drug screening, and regenerative medicine.-Ramunas, J., Yakubov, E., Brady, J. J., Corbel, S. Y., Holbrook, C., Brandt, M., Stein, J., Santiago, J. G., Cooke, J. P., Blau, H. M. Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.

Telomere extension turns back aging clock in cultured human cells, study finds

http://med.stanford.edu/news/all-news/2015/01/telomere-extension-turns-back-aging-clock-in-cultured-cells.html#!

Researchers delivered a modified RNA that encodes a telomere-extending protein to cultured human cells. Cell proliferation capacity was dramatically increased, yielding large numbers of cells for study.

Jan 22 2015

Helen Blau

A new procedure can quickly and efficiently increase the length of human telomeres, the protective caps on the ends of chromosomes that are linked to aging and disease, according to scientists at the Stanford University School of Medicine.

Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying.

The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development, the scientists say. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases caused by shortened telomeres.

Telomeres are the protective caps on the ends of the strands of DNA called chromosomes, which house our genomes. In young humans, telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division, however, and when they reach a critical length the cell stops dividing or dies. This internal “clock” makes it difficult to keep most cells growing in a laboratory for more than a few cell doublings.

‘Turning back the internal clock’

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life,” said Helen Blau, PhD, professor of microbiology and immunology at Stanford and director of the university’s Baxter Laboratory for Stem Cell Biology. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.”

A paper describing the research was published today in the FASEB Journal. Blau, who also holds the Donald E. and Delia B. Baxter Professorship, is the senior author. Postdoctoral scholar John Ramunas, PhD, of Stanford shares lead authorship with Eduard Yakubov, PhD, of the Houston Methodist Research Institute.

The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell’s protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase. Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.

Transient effect an advantage

The newly developed technique has an important advantage over other potential methods: It’s temporary. The modified RNA is designed to reduce the cell's immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would. But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division.

The transient effect is somewhat like tapping the gas pedal in one of a fleet of cars coasting slowly to a stop. The car with the extra surge of energy will go farther than its peers, but it will still come to an eventual halt when its forward momentum is spent. On a biological level, this means the treated cells don’t go on to divide indefinitely, which would make them too dangerous to use as a potential therapy in humans because of the risk of cancer.

This new approach paves the way toward preventing or treating diseases of aging.

The researchers found that as few as three applications of the modified RNA over a period of a few days could significantly increase the length of the telomeres in cultured human muscle and skin cells. A 1,000-nucleotide addition represents a more than 10 percent increase in the length of the telomeres. These cells divided many more times in the culture dish than did untreated cells: about 28 more times for the skin cells, and about three more times for the muscle cells.

“We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase,” said Ramunas. “Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious. In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent.”

Potential uses for therapy

“This new approach paves the way toward preventing or treating diseases of aging,” said Blau. “There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment.”

Blau and her colleagues became interested in telomeres when previous work in her lab showed that the muscle stem cells of boys with Duchenne muscular dystrophy had telomeres that were much shorter than those of boys without the disease. This finding not only has implications for understanding how the cells function — or don’t function —  in making new muscle, but it also helps explain the limited ability to grow affected cells in the laboratory for study.

The researchers are now testing their new technique in other types of cells.

“This study is a first step toward the development of telomere extension to improve cell therapies and to possibly treat disorders of accelerated aging in humans,” said John Cooke, MD, PhD. Cooke, a co-author of the study, formerly was a professor of cardiovascular medicine at Stanford. He is now chair of cardiovascular sciences at the Houston Methodist Research Institute.

“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful,” said Blau, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

“One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy.”

Other Stanford co-authors of the paper are postdoctoral scholars Jennifer Brady, PhD, and Moritz Brandt, MD; senior research scientist Stéphane Corbel, PhD; research associate Colin Holbrook; and Juan Santiago, PhD, professor of mechanical engineering.

The work was supported by the National Institutes of Health (grants R01AR063963, U01HL100397 U01HL099997 and AG044815), Germany’s Federal Ministry of Education and Research, Stanford Bio-X and the Baxter Foundation.

Ramunas, Yakubov, Cooke and Blau are inventors on patents for the use of modified RNA for telomere extension.

Information about Stanford’s Department of Microbiology and Immunology, which also supported the work, is available at http://microimmuno.stanford.edu. 

Nowinki z Internetu: silnik kwantowy

Na Marsa w dwa dni, na Księżyc w 3,6 godziny

http://wolnemedia.net/nauka/na-marsa-w-dwa-dni-na-ksiezyc-w-36-godziny/#!

Opublikowano: 05.02.2015

Niezwykły prototyp rosyjskiego inżyniera może być początkiem prawdziwej rewolucji porównywalnej chyba tylko z wprowadzeniem silnika parowego i silnika spalinowego. W 2009 roku Władymir Leonow opublikował wyniki testów jakie przeprowadził na silniku kwantowym, którego prototyp ma być 5 tysięcy razy bardziej efektywny silnika rakietowego.

Jak twierdzi Leonow prace nad projektem wciąż nie wyszły poza etap prototypów, jednakże w czerwcu 2014 roku udało się osiągnąć niezwykłe wyniki: ważący zaledwie 54 kilogramy silnik był w stanie zużywając 1kW energii elektrycznej wystartować z przyspieszeniem 10-12g i osiągnąć ciąg o wartości 500-700 kilogramów-siły.

Sam Leonow twierdzi, że jego odkrycie dokona prawdziwej rewolucji w świecie, jego silniki zużywają ułamek energii potrzebnej tradycyjnym silnikom odrzutowym, ponadto zwiększy się maksymalna prędkość jaką będzie on w stanie osiągnąć. W przetłumaczonym na język polski wywiadzie utrzymuje on, że statek kosmiczny z nowym napędem będzie w stanie osiągnąć prędkość 1000 km/s (przy 18 km/s „zwykłej” rakiety), co oznacza, że czas lotu na Marsa skróci się nawet do 42 godzin, podczas gdy na Księżyc będziemy w stanie dolecieć już w 3,6 godziny.

Brzmi niesamowicie? To nie wszystko, również na Ziemi loty staną się znacznie bardziej opłacalne a przy tym szybsze, nowy rodzaj samolotu będzie w stanie pokonać trasę z Moskwy do Nowego Jorku w godzinę (teraz leci ok. 10 godzin) zużywając przy tym tak znikomą ilość paliwa, że tankować będzie musiał co kilka lat.

W końcu samochody – one również się zmienią, ich żywotność niezwykle wręcz wzrośnie,osiągając 50-100 lat, do tego wyposażone w poduszkę antygrawitacyjną zaczną latać.

Fantastyka? Leonow twierdzi, że jego prototyp jest jak najbardziej prawdziwy i technologia ta leży w zasięgu ręki, twierdzi też, że ma ona stać się motorem do nowego rozwoju gospodarczego Rosji. Czy tak sie stanie?

Wyniki jego testów można obejrzeć na blogu Leonowa – Quantum Energetics.#!

Autorstwo: Victor Orwellsky
Źródło: Kod Władzy#!

Results of the tests of a quantum engine for generating thrust without the ejection of reactive mass

http://theoryofsuperunification-leonov.blogspot.ru/2011/05/results-of-tests-of-quantum-engine-for.html#!

From the book Leonov V. S. Quantum Energetics. Volume 1. Theory of Superunification. Cambridge International Science Publishing, 2010, pp. 694-689.

10.9.1. Results of the tests of a quantum engine for generating thrust without the ejection of reactive mass

Up to now, the reactive method was the only method of producing thrust in vacuum. It is based on the ejection from the nozzle of reactive mass during the combustion of fuel in the jet engine. It is considered that the gas pressure during the combustion of fuel acts on the internal walls of the jet engine and produces thrust. The thrust momentum is proportional to the speed and mass of the fuel ejected from the nozzle.

Numerous attempts have been made to produce thrust without the ejection of reactive mass. These were purely empirical attempts within the framework of the existing knowledge. Without having clear theoretical substantiation, it was impossible to create such an engine. The point is that in accordance with the third Newton’s law, when effective force is equal to the counteracting force, thrust is created with repulsion from another mass or body. The wheels of an automobile are repulsed from the road surface. In the jet engine, the thrust is created as a result the ejection of reactive mass, as if being repulsed from this mass. Air and hydraulic screws, screwing into the air and hydraulic medium, reject the mass of this medium, being repulsed from it.

But is it possible to be repulsed from vacuum? The theory of Superunification asserts this is possible by considering space vacuum as the elastic quantised medium (quantised space-time) from which it is possible to be repulsed. This is the unique weightless medium which has not analogs in nature and whose structure is described for the first time in the theory of Superunification. It is shown that the weightless quantised space-time penetrates through all ponderable bodies. In this case, all ponderable bodies are the composite and indissoluble part of the weightless quantised space-time. The mass of a body is formed as a result of the spherical deformation (bending according to Einstein) of the weightless quantised space-time by elementary particles which form part of the body. In this case the mass of the body is the component part of the elastic quantised medium, its energy cluster. Mass, as a gravitational charge, is a secondary formation in the quantised space-time.

All known methods of producing thrust are based on the external action with the repulsion from the known media. In this case all known apparatuses for the thrust generation must be treated as closed quantum-mechanical systems. In accordance with the theory of Superunification, the quantum engine is an open quantum-mechanical system when thrust is created inside the body of the operating unit (activator) of the quantum engine. To create thrust without the ejection of reactive mass it is necessary to switch over to the open quantum-mechanical systems, treating quantised space-time as an elastic quantised medium. Consequently, it is possible “to push away” from such an elastic quantised medium thus generating thrust. In this case, there are no contradictions with third Newton’s law, whose fundamentality is thoroughly checked, and is completely confirmed by the theory of Superunification. The reader should refer to the section 3.5.3. Simple quantum-mechanical effects, and also to patent [9].

The very process of creating the thrust inside the operating unit of the quantum engine is connected with Einstein’s ‘bending’ of the quantised space-time. Based on the positions of the theory of Superunification, the Einstein distortion effect of space-time looks like the real deformation of the elastic quantised medium inside the operating unit of the quantum engine [9]. This deformation produces the redistribution of the quantum density of the medium inside the body of the operating unit of the quantum engine. This leads to the appearance of gradient thrust forces inside the operating unit. Thus, for the first time gravity and inertia are controlled. This again confirms the fundamentality of Einstein’s theory that against the basis of gravity is the bending of the quantised space-time.

It is natural that the control of gravity on the global scale is not possible at the moment. The perturbing mass of the Earth is required to obtain the strength of the gravitational field of 1g (acceleration in the terrestrial gravitational field) in pure vacuum. This deformation of the outer space free from the external source is is associated with colossal power consumption.

But here the deformation of the quantised space-time in the local region inside the operating unit (activator) of the quantum engine already corresponds to energy which is spent by the body on its acceleration. In this case the classical law of energy conservation. Deformation of vacuum takes place in the body of the operating unit of the quantum engine which actively interacts with the vacuum medium which penetrates the body. The internal thrust force appears inside the body of the operating unit. This is not external repulsion as in the jet engine, it is internal repulsion. Therefore, without having new knowledge, it was not possible in the pas to analytically predict such processes and effects.

But the theory of Superunification goes further and differs from the classical theory by the fact that it is the very strongly developed quantum theory which operates with the already superstrong electromagnetic interaction (SEI) as the basic, previously unknown energy source in the universe. For comparison, the classical theory forbids motion without the ejection of reactive mass, whilst the theory of Superunification permits this motion. It is gratifying that during motion with acceleration regimes form inside the quantised space-time in which deceleration is observed during energy regeneration. With recuperation the spent energy returns and can be used for the second time. Such regimes are used in the hybrid circuits of automobiles with electric transmission. The kinetic energy of a moving automobile with its braking is restored and returns to the energy accumulator – the storage battery. With the acceleration of the automobile the stored energy is used for the second time. In this case, the fuel consumption in the regimes of frequent acceleration and braking is sharply reduced. Inertia possesses a remarkable property - capability for regeneration.

Inertia regimes with regeneration are used actively in the quantum engine. The capability of the quantum engines for energy regeneration during thrust ensures the most economical power cycles of the quantum engine. It is necessary to compensate the energy losses due to friction in the mechanisms of the engine and ohmic losses in the electrical wires and the windings of the activators. In comparison with the traditional internal combustion engine (ICE) and the jet engine, the efficiency of the quantum engine for the generation of thrust can exceed that of the traditional engines 20 or more times. Let us compare the regimes of motion of an expedition to Mars along the ballistic trajectory as far as the inertia and the trajectories of motion in the regime of acceleration - braking with regeneration are concerned. In both cases, the path integral which determines power consumption for motion, excluding losses, is equal to zero. However, in the case of motion the acceleration-braking regime, using a quantum engine, we repeatedly gain in the duration of the expedition, completely compensating weightlessness [9]. In this case, the quantum engine works in the regime of constant conversion and energy exchange of superstrong electromagnetic interaction (SEI).

It would seem that the patent [9] describes in a simple manner the construction of the operating units (activators) of the quantum engine and the principle of its operation. But this is done only theoretically. The patent does not stipulated the modes of powering the operating units and the materials from which they are made. Even the author of this development had to face serious problems in creating the quantum engine and determining the thrust regime during operation of the engine. Two years of intense work were required for this. It was encouraging that immediately it was possible to generate a small thrust of 0.1 N, and this thrust was then further increased.

In two years (2007-2009) of experimental work it was possible to increase the thrust from 0.1 N to 500 N with the mass of apparatus being 50 kg together with the chassis. The diameter of the apparatus of was 1.5 m, the height 1.05 m together with the chassis (photo). It can be concluded that the earth’s gravity was overcome with the aid of the quantum engine. Outwardly the apparatus resembles a small flying saucer (or saucepan), but this does not mean that the apparatus must have the form of a ‘plate’. It can be any form. Unusual even for the author was to observe the motion of the apparatus which has no screws, jet nozzle and drive for the wheels. High stability is typical of the work of the quantum engine. The effect of generating thrust without the ejection of reactive mass during the operation of the quantum engine did not disappear even after 6 months in repeated tests. This fundamental effect is always well reproduced. An apparatus with the thrust of 5000 N weighing 100 kg is being prepared for tests. If everything goes without problems, then its flights will be demonstrated at the Moscow Aerospace Salon (MAKS) at Zhukovskiy in the Moscow region. The results of tests and design features of the quantum engine, the procedure for calculation of operating units for the given thrust and the operating modes, will be examined in the second volume of Quantum Energetics.

In principle, there are no special limitations on the thrust of quantum engines. A procedure has been developed for calculation of the design parameters of the quantum engine for any thrusts, including 100 tons (1000 N), 1000 tons (10000 N) and more. High efficiency is the distinctive special feature of the quantum engines since the quantum engines do not use the uneconomical thermodynamic cycles. They use exchange cycles inside the energy-consuming quantised space-time. The construction of interplanetary spacecraft of the new generation with the complete compensation for weightlessness becomes reality. The organization of an international expedition to Mars with the participation of the European Union, USA and Russia and other countries will become possible.

It should be noted that the quantum engine is a relatively complex construction with the complex electronic control system. It is an expensive apparatus and its repeated construction can be ensured only by powerful organizations with the participation of specialists in the region of the theory of Superunification. However, no specialists are being trained in this area at the moment. It is hoped that when this book is published, its content will be accepted the university courses of physics and power engineering, giving new knowledge to future specialists.

On the other hand, the efficiency of the quantum engine is the thorough experimental verification of the theory of Superunification which predicted similar effects and they have been confirmed experimentally. Most importantly, the efficiency of the quantum engine proves that the vacuum has a structure in the form of quantised space-time with which it is possible actively to interact. Prior to starting the series production of quantum engines, it would be desirable for independent laboratories to study of the processes of the interaction of the simplest operating units with the quantised space-time, investigating its elastic properties. This is new knowledge which will have to be acquired. A simple and inexpensive instrument, which can be repeated in any university laboratory, has be constructed and is proposed for repetition below, or it can be ordered from us.

9. Leonov V.S. Russian Federation patent No. 2185526. A method of generation of thrust in vacuum and a field engine for a spaceship (variants), Bull. 20, 2002.

Video: The tests 2009 of a quantum pulsed engine for generating thrust without the ejection of reactive mass.