Here we will post summaries of ideas or discussions by our researchers


OUR LATEST PROJECT

An e-Book project on 'Challenging Ageing' which will examine the role of the environment, hormesis, information and stimulation in up-regulating health-related biological processes. The purpose is to show that, as our environment changes in the technological sense, our biology also changes, and we speculate that these changes will have an impact on age-related degeneration. Estimated completion and publication: by the end of 2016.

This also discusses the Indispensable Soma hypothesis.

 

 Other Projects 

Integral-Component-Replacement-Therapy

By Franco Cortese

This is a 3-part project with team-members Francesco Cortese, Marios Kyriazis MD, M.Sc, MIBiol,CBiol and Giovanni Santostasi, Ph.D. that aims to investigate proposed therapeutic strategies for use in regenerative medicine (Recurrent mtDNA Replacement Therapy, Recurrent gDNA Replacement Therapy, and Induce Whole-Body Somatic-Cell Turnover), each of which are encompassed by an underlying therapeutic strategy called integral-component-replacement-therapy that aims to replace affected cellular components and systems with error-free copies synthesized in-vitro, rather than addressing each category of age-associated phenotypic deviation on its own terms (i.e. by attempting to directly modify the development and maintenance of the category of damage itself, or by attempting to modify affected cellular components or systems in such a way as to be able to function despite the continuing accumulation of such categories of damage).

The first project, Recurrent mtDNA Replacement Therapy, analyzes the possibility and viability of using gene-vectors to recurrently replace mtDNA with error-free copies synthesized (e.g. via oglionucleotide synthesis) and multiplied via therapeutic cloning en-masse by polymerase-chain-reaction or molecular cloning in order to periodically negate accumulated mtDNA damage.

The second project involves using the same technique to negate accumulated gDNA damage. While gDNA is far too large to replace whole-sale (due to limits on the packaging-size of contemporary gene-vectors), only a small fraction of gDNA has identified protein-coding or epigenetic function, and the large majority is thought to have no protein-coding, regulatory or epigenetic function. Thus, the project will analyze the possibility of replacing the functional portion of gDNA with error-free copies excluding all identifiable non-functional non-coding sequences, thereby allowing it to be replaced via transfection techniques in a manageable number of phases.

The third project will involve analyzing the possibility and viability of a single therapy aiming to negate 5 identified categories of accumulated age-associated phenotypic-deviation: mtDNA damage, gDNA damage, cell loss, accumulation of post-mitotic cells and accumulation of intracellular lipofuscin. The conceptual therapy, Induced Whole-Body Somatic Cell Turnover, involves the prospect of subjecting a small portion of the cells constituting bodily organs and tissues to programmed cell-death and replenishing such organs and tissues with stem-cells, in a number of phases, gradually, until every cell in the body's organs and tissues have been subjected to PCD and replaced with stem-cells. By subjecting cells to this therapy gradually, organs and tissues can retain their function throughout each phase of the therapy.

An objective of the project will be to determine whether cell turnover can be safely and periodically implemented at the rate required to achieve complete whole-body-cell-turnover before accumulation of age-associated damage in each of the 5 categories leads to overall functional decline. Other aspects of the project include an analysis of methods of targeted stem-cell migration inside the body and methods of selectively targeting tissue or organ-specific cells for PCD.

 


 

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Comments on energy, entropy and society, with regards to Biological Immortality

By Jonah Lissner and Manuel Teixera (edited by Marios Kyriazis)


Let us suppose that in order to influence the mechanisms that may lead to extreme lifespans, we need to transfer a large amount (perhaps an  infinite amount) of information into the body (brain and other structures). The rationale for this has been explained elsewhere  (basically it is grounded on the premise that more information equals more neurobiological complexity and thus an increased likelihood of extreme brain longevity). This process needs to be very quick -it would be a 'singularity-type' process. If we utilise real time, the process will be endless (regardless of the speed of the process). Therefore, we need to utilise imaginary time instead. Using imaginary time, one can  manipulate infinite information in a finite amount of real time, and so the problem is solved.

The ageing process is basically a process where entropy is  increasing.Entropy, defined as 'loss of energy', is an increasingly changing state and not necessarily disordered, but perhaps 'unordered' compared to the initial state. There is no loss of energy- only transfer of energy in vibrational frequencies as wave functions and strings which  explain some of the complexity and dimensionality of bounded domains (see term).

So, what we need is more information (also called negative entropy) and the right information, in order to force the entire organism to operate in a perfect functioning state. This will eliminate entropy "in real time", so to speak. More information will lead to more intellectual complexity, as well as more biological redundancy, i.e. less risk of ageing and death. One basic and practical (but slow) way, utilising real time, for achieving this is through a lifestyle-dependant process of increased input of information and stimulation of the brain and body. See, for example Kyriazis' papers:

http://www.ncbi.nlm.nih.gov/pubmed/12766532

http://www.ncbi.nlm.nih.gov/pubmed/20662589

However, this does not allow for a quick transfer of information. According to the above singularity-type model, there are two basic parameters: the information (that must be infinite for theoretical reasons), and the consequence (the global entropy must decrease to zero).

Prof. Frank Tippler utilised a simple mathematical model to explain how an infinite amount of information could be "injected" in a finite amount of time. Let us suppose we consider the function 

y = tan x 
and we take the interval
[ - π/2 ; + π/2 ] . The values of the function between this finite interval go from - ∞ to + ∞.

The theory of punctuated equilibrium defends that important changes in biological beings are made in a very quick way (a singularity process) instead of a very slowly process.

We also have to define 'informational energy' (IE) which is composed  of:

* available energy (aE)

* usable energy (uE)

* latent electronic energy (leE)

* magnetic energy (lmE)

In addition, there is a time-dependent energy i.e. entropic energy (eE).

These energies are utilized by any given entity to the extent of its biological or material capacity, and we need to study methods of channelling progressively increasing IE through neurobiological domains in progressively less time. The matter of complexity of information is the complexity of given packets of aE, uE, and lE etc. for each entity usable as input, and the complexity of given packets of aE, uE, lE etc. internally across a timeline for each given entity or system.

A possible way for injecting Informational Energy is via sociocultural applications, where we can envisage and plan bio-computing,  renewable/green cities for the future, utilizing holographic learning tools and manufacturing goods with massive and harmonic potentials for all of their citizens. All of these will play a part in increasing IE both at the level of the individual and that of the society as a whole. The building of efficient societies that can support indefinite human lifespans is relevant here. It appears that if there is co-operation/synergy between the society and its human member, both will eventually live extremely long lifespans (i.e. both will 'survive' in the evolutionary sense, i.e. a 'win-win' scenario).

For information see:

http://uncomp.uwe.ac.uk/adamatzky/papers.html

http://en.wikipedia.org/wiki/Biocomputers

http://en.wikipedia.org/wiki/Information_entropy

www.linkedin.com/pub/jonah-lissner/3b/43a/784

 

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Transposable elements and longevity

by Andreas Apostolides


Based on theories proposed by Marios Kyriazis

This project is based on a hypothesis first proposed by Marios Kyriazis as part of his ELPIs theory. The hypothesis states that there are certain transposon (described below) in humans that either promote or repress longevity, and that it may be possible for us to enhance longevity by either increasing the function of those transposons that promote longevity or decreasing the function of those that repress it.

Transposons are DNA segments that have the ability to move within the genome either by being removed from one place and then  integrated into another (these are called "DNA transposons"), or by first being transcribed into RNA and then reverse-transcribed into cDNA which is then integrated into another place of the genome (these are called "retrotransposons"). About 45% of the human genome consists of recognizable transposons (Lander, et al. 2001).

Because when they were first discovered it was believed that these elements code for no protein at all and have no effect on the expression of genes, they were initially considered as part of at~94%of DNA they used to call "junk DNA". This soon changed, however, as it begun being revealed that transposons, either readily after their integration in the genome or after minor nucleotide changes in their sequence,can acquire new functions leading to the expression of novel genes or affecting the expression of other genes.

Specifically, transposons can either offer themselves as protein-coding regions (either because they had been inserted inside a gene's exon, or due to more complex mechanisms that will not be described here), or they can affect the expression of nearby genes by offering themselves as splice sites, polyadenylation signals, or transcription  regulatory elements such as promoters, transcription enhancers, transcription silencers, transcription inhibitors, etc (see Brosius, 1999, for many examples).  Such phenomena, where elements acquire new functions, are called exaptations (see Gould and Vrba 1982)

It is already known that there are certain genes that promote and others that repress longevity (for example by increasing chances of development of certain diseases). It is also known, as discussed above, that transposons can contribute novel genes, or they can affect the expression of existing ones. The purpose of this project is to  examine whether there are existing transposons that contribute to our longevity in a way described by Kyriazis' theory. Specifically, we are interested in:  
        
Transposons that contribute to the expression of longevity genes     
Transposons that inhibit the expression of mortality genes

For the time being we will concentrate on the first part: Transposons that contribute to the expression of longevity genes. This could be happening in various ways, but at first, we will be examining the following scenarios: 
      
A transposon being a part of the protein-coding region a longevity gene
       
A transposon serving as a longevity gene's promoter

     
A transposon serving as a splice site that makes possible the creation of a longevity gene transcript

      
A transposon serving as apoly(A) signalthat makes possible the  creation of a longevity gene transcript.

References:

BROSIUS, J., 1999. RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements.Gene,238 (1), 115-134.

GOULD, S.J., and VRBA, E.S., 1982. Exaptation-a missing term in the science of form. Paleobiology,8 (1), 4-15.

KYRIAZIS, M.,The ELPIs Theory, Research Directions, http://www.elpistheory.info/page4.htm

LANDER, E.S.,et al., 2001. Initial sequencing and analysis of the human genome.Nature,409 (6822), 860-921.

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One of the best insights from the following article is the idea based on synergy between societal systems and individuals living in such societies. A society which promotes an extreme lifespan of its human members will itself experience an extreme lifespan and will 'survive' in the evolutionary sense. This is a 'win-win' situation which is believed to be an optimal scenario within modern evolutionary ethics.


Immortality, Humanity, and the Persistence Pattern

by 'capob' (Adam Frederick)

Here I will try to explain the future of humanity, the possibility of immortality, and the relation of these things to persistence.  To cut to the chase, I will first go into the tool used for analysis.

Natural selection needn't be limited in application to organisms.  In applying natural selection more broadly in what I call a persistence pattern, I modify Darwin's statement of, "But, if variations useful to any organic being do occur, assuredly individuals thus characterized will have the best chance of being preserved in the struggle for life", to, "But, if variations useful to any system do occur, assuredly systems thus characterized
will have the best chance of persisting".  And, you can apply this pattern of persistence towards atoms forming compounds or market driven efficiency or many other things.

Technology is a natural product of this persistence pattern.  In a sense, this persistence pattern is a matter of optimization.  Where, before, you had phone operators manually connecting callers, now systems do this automatically in a much faster, an optimized, fashion.  And, this pattern of optimization will continue so long as there are further optimized states which are reachable from current states.

The non-reachability of more optimized states, or prevention of optimization, can take the form of resource unavailability or super systems preventing sub system optimization.  To put the latter case in more grounded terms, cultural or societal paradigms can prevent optimization.  Similarly, power monopolies can prevent optimization.  A power   monopoly can be likened to a solitary creature on an island; it doesn't matter whether the creature is maladapted to its environment, it will not be replaced through natural selection because it is the only creature on the island.

Assuming that the persistence pattern continues to lead to further optimization, there are various things we can extrapolate.  If the only effect of this persistence pattern on humanity were to optimize un-pleasurable tasks and to favor pleasurable tasks, we would be seeing a much different world.  Instead, what we have is a scenario where many non-human drivers drive the creative minds that fuel progress, and consequential progress is implemented in ignorance of, for the most part, how the progress will affect the pleasure and pain of the humans who encounter it. 

Non-human drivers of progress are largely derivatives of human desires. For example, a company, in an effort to make more money for the human owners sets out to optimize, drive progress, its internal systems.  And, the internal systems of this company could be just about anything - like extracting oil, harvesting crops, surveying citizenry, providing news. 

As a result of non-human drivers, one cannot negate the emergence of AI or bio-mechanical integrated systems just because such things don't benefit humans.  Instead, regardless of whether AI systems or human augmentation improve the quality of life of humans, these things will emerge by the fact they are reachable optimized states.

And, now, getting into immortality, the issue is how AI or human augmentation will influence the long life and potential immortality of the individual.

There are many overlapping ways to categorize augmentation, and I initially wrote this part going into a few of them, but instead, I will explain a simple dynamic.  The degree that an augmentation is integrated with the human brain is a reflection of humanity's understanding of the human brain, and when the human brain is understood conceptually, in can be reproduced programmatically. And, when the human brain can be reproduced, AI can be formed.  And so, even assuming augmentation will move forward quicker than AI, at some level of brain integrated augmentation, there will be AI, and then the question will be a matter of optimization.

The matter of optimization when it comes to AI has a number of parts.  The human brain is a very complex and efficient bio-computer, and reproducing it with a non-bio-computer has a large potential expense; however, there are a couple of downsides the human brain has when compared to a computer brain:


    1.  The human brain is isolated with a small bandwidth for interfacing with other systems.  This bandwidth takes the form of language and body movement.

    2.    The human brain may not be able to scale upwards.  IE, it's architecture is fixed and would not support expansion without extensive re-architecting.

    3.  The human brain has limited linear computational ability; and, as computers advance, the human brain will also be seen to have limited non-linear computational ability (non-linear being multi process entity relation computations).


Technological advancements have resulted in an increased complexity in systems.  The growth of this complexity in consideration of human operators has led to two things:

    1. interfaces with more complex back ends and relatively simple front ends.

    2. humans with more aptitude for semi-technical matters.

The nature of the increased complexity in the back end of the system is represented by the increased number of actions per each user action.  An action by a user in a user interface represents some desire for action by the system.  A simplified example of this:

    Going from:
        User types in 11 buttons to call a friend on phone (phone number + call button)

    To:
        User types 2 buttons to call a friend on phone (recent calls, call button)

The increased complexity of the back end is simplified on the front end by anticipating user actions and grouping low-level actions on concepts the user can select from.  This forward movement of technology with increasingly complex systems while having a relatively simple user interface for the human operator has a limit.  The limit comes in two forms.  The first form is when the number of distinct concepts necessary to operate the system becomes too large for many human operators to conceive of in a reasonable amount of time or to enter into the system in a reasonable amount of time.  Consumer electronics do not have this problem, as they are designed specifically to be used by humans.  However, as governments and corporations implement increasingly complex systems, they will find human operators of those systems less and less capable of operating the systems, and they will rely more and more on algorithmic system behavior.  This algorithmic system behavior eventually equates to AI system control.

The nature of any open system attempting to gain absolute control of a thing is to expand into other systems to gain control over formerly outside variables that influence the system's control over the thing.  In terms of companies, this can be seen as vertical expansion.  In addition to this,integration of systems with other systems often represents an optimized state.  When a governmental center for disease control is integrated into a system like google that has the ability to anticipate the emergence and spread of epidemics based on user actions, there is a greater ability for the center for disease control to control an epidemic.  Or, when traffic systems (currently represented by traffic control lights) are integrated with automobiles, there is a greater ability to optimize the flow of traffic.

This system expansion and integration has the effect of increasing complexity of the systems and decreasing the ability of human operators to operate the systems at any level apart from a very abstracted, high level.  This expansion and integration also has the effect of decreasing the number of systems which are not complex.  And, the effect of these things is to decrease the need for human operators.  And, as a result, jobs are in the form of three categories:

    1.  Jobs in which robots have not yet economically outperformed humans.

    2.  Jobs building systems while the systems can't build themselves

    3.  High level, abstracted control of systems.


And, so, we have a scenario in which AI and robotics will largely replace humans in terms of controlling systems at any level other than high level.  And, when I say high level, I refer back to the part in which a user interface is simple where the back end is complex by having an increasing number of back end actions corresponding with each single user actions.  For example, a user action might be to say "raise taxes", after which, the system set up to calculate and collect taxes changes to follow the command of raising taxes, and this system change has the potential to be equated to greater than millions of "back end" actions.

A person seeking immortality amid the above eventualities has hope of finding it in two places.

The first idea of a place to find immortality is with the idea that the increasingly complex systems will simply serve to accommodate the pleasure and pain desires of some number of humans.  An example of this would be the example put forth in the movie WALL-E.  This idea, however, appears to ignore the fact that the emergence of such complex systems came from non-human driven demands, and a likely consequence of this is that the systems will not stop optimizing to accommodate human driven desires.  It is a common notion that in the creation of AI, humanity will get a "bad" AI that turns on its creators.  I would look at the scenario in a much less "good" and "evil" light.  Any system AI will do just what we have done; it will optimize the system, and if that means discounting the needs of humans, that is precisely what it will do.

The second idea of a place to find immortality is in uploading the mind into a computer and having persistence of that mind in a computer system.  The idea that the mind will persist in a controlling fashion is rather trivial to disprove.  As a human, the personality traits and characteristics that one might consider defining oneself are largely irrelevant when considering optimizations of systems and AI control of systems. In other words, when human minds are built into systems with much higher bandwidth capacity, not only are the personality traits stemming from the limitations and capabilities of the human body irrelevant, the whole language that the human mind knew and used to
communicate becomes largely obsolete in the presence of much more efficient forms of computer system communication.

And so, there is no immortality of the "self".  Instead, you will have longevity while the technology does not make you obsolete, and in considering the persistence of the brain, the knowledge and algorithms in your brain that are useful may be used for the time they stay useful, but this extraction only represents a continuation of self to the extent that something like extracting the knowledge of arithmetic from a brain represents a continuation of the "self" of that brain.  And, where you once had individuals, you will have largely interconnected systems with standard libraries of algorithms - a sort of modular hive-mind.

   
In conclusion, there are two questions that come in consideration of the ideas herein presented.  The first:  "Do we want to follow this persistence pattern?" Of course, even if the answer were no, can one actually stop progress?   There are various ways in which progres can be halted:

    1. Societal paradigms or systems getting "stuck".

    2. Elimination of humanity on Earth by humanity or natural disaster

    3. Societies reducing themselves to previous, more primitive states.  Potentially, societies can bomb themselves back to the stone-age, or can crumble by corruption.  And, in these scenarios, societies can rise and fall in an infinite loop and never progress out of the loop.

The second question is: "What will we do in between now and being made obsolete?".  Well, for those who want to live as long as possible, I imagine working towards advances in health maintaining technologies and medicines would be the way to go.  After all, you can always hope for future "nature preserves" where you, as a human, can live forever foraging around in the "wilderness" of some former city with your life sustaining technologies in a park maintained by T1000 park rangers.  For people like me, I care to build useful societal systems that help to both promote progress and better the life of the members of the society; and, there are certainly synergies between building such societal systems and the longevity of the societal members.  And, making the choice to progress instead of attempting to stop progress, a society based on a persistence goal may help to avoid the ways in which progress can be halted.  But, what to do in the interim is really just a matter of taste.



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