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Extreme Lifespans though Perpetual-Equalising Interventions (Human Biological Immortality)

Posted: Wed, January 16, 2013 | By: Indefinite Life Extension



by Mario Kryiazis

In this article I will outline the hypothesis that Human Biological Immortality (HBI) is an inevitable consequence of natural evolution. I will then discuss possible ways for accelerating this process through the notion of ELPIs (Extreme Lifespans though Perpetual-Equalising Interventions).  The discussion is based on existing scientific evidence or learned speculation.

Part 1. Evolution

Nature works inexorably in a way that increases self-organising complexity and dynamical variability. In the history of the universe, simple initial events progress hierarchically to reach higher levels of complexity.

It is beyond the scope of this discussion to present proof that this is so. Nevertheless, it generally accepted that the highest level of complexity and self-organisation currently possible is encountered within human neural tissues i.e. human intelligence. 

The universe started approximately 14-20 billion years ago, when the basic laws of nature came into existence. Universal self-organisation increased gradually until approximately 4 billion years ago, when organic life was formed. More complex life was in place by 200 million years ago when, through evolution by natural selection (Darwinian evolution), the complexity and sophistication of living systems progressed steadily to more advanced levels until homo sapiens sapiens (modern human) appeared about 200 thousand years ago.  We have been steadily evolving since, and we are now in a position to actually interact with, influence, and manipulate our environment through ever-increasing technological and cultural developments.

At this stage, it would be useful to discuss the notion of the Singularity, particularly the Technological and Developmental Singularities (see www.accelerationwatch.com). In short, this holds that progressively more will be achieved in progressively less time.  According Acceleration Watch, this is based on:

“…the idea that the most complex of the universe’s extant systems (galaxies, stars, habitable planets, living systems, and now technological systems) use progressively less space, time, energy and matter (“STEM”) to create the next level of complexity in their evolutionary development”. http://en.wikipedia.org/wiki/John_Smart_(futurist)

Therefore, in order for human intelligence to evolve further it will be necessary to use progressively quicker means, and so the slow process of evolution by natural selection will become gradually less relevant in the development of human intellectual sophistication.

Instead, humans will continue to evolve via a Developmental Singularity process (www.accelerationwatch.com/developmentalsinghypothesis.html) which means that increasingly more sophistication will be achieved in progressively less time by digitally-assisted biological development within the same neural structures of an individual, who would gradually become transhuman. This has already begun and will continue over the next several decades (i.e. not thousands or millions of years as it has hitherto been the case).

This is profoundly important as it shows that, in order for natural laws to be obeyed, human intelligence must develop quickly, and the way to achieve this is through self-development and not through natural selection – a slow, clumsy, ‘hit and miss’ process that is based upon trade-offs between reproduction and longevity. It follows that humans must live for a long time if this is to be achieved.  Further development will be possible with the use of technology and societal changes which will facilitate individual humans become members of a super-human, super-intelligent self-conscious system – and the first already existing step is the internet.

Inherent in the above is the notion that, Darwinian evolution which necessitates that all living creatures (in this case, humans) must die quickly and be replaced (a process described by the Disposable Soma Theory  http://www.programmed-aging.org/theories/disposable_soma.html) in order for natural selection to take place, will become redundant.

Evolution by natural selection is merely a tool used by nature in order to facilitate development. Its presence is not eternal, and when it serves its purpose, nature will discard it, just as it discarded other tools needed for attaining organisation and complexity, such as Inflation (in the case of Big Bang) and Abiogenesis (in the case of the origin of life). 

If evolution by natural selection becomes redundant, then it means that humans will not have to die through ageing and senescence. It is worth noticing here that contrary to commonly-held belief, from nature’s point of view, the DNA is not any longer the most important vehicle for achieving adaptive complexity. Instead, neural tissue is the new suitable vehicle for attaining progressively advanced intellectual sophistication. 

Nature will follow whatever paths are necessary in order to increase hierarchical sophistication even if this means the end of human evolution by natural selection. In the pursuit to become more complex (and therefore create higher intelligence), natural laws transcend individual races, species (including their DNA), systems or galaxies. 

Higher complexity can now be achieved through technology-assisted human intelligence, within the context of an ever-evolving society influenced by humans which, in turn, influences and augments the development of that intelligence. It is necessary therefore for these neural tissues (and thus, our body) to remain alive long enough for the process to be accomplished. Thus death by ageing becomes redundant.

Basic natural laws of physics, chemistry, biology and mathematics have shaped the process of the origin of life, which has been augmented by the process of evolution by natural selection to form modern humans.  We are now using our own intelligence and technological resources so that to accelerate the process of evolution and self-organisation in order to evolve into transhumans - one of the characteristics of which is biological immortality.

Part 2. Accelerating the process

If it is assumed that the above discussion is, on the whole, correct, then one may ask the question: Can we intervene in any way in order to accelerate or modify this process? I propose that there are several ways by which we can intervene and try to influence the process of Human Biological Immortality. My ELPIs theory holds that apart from the fact that human immortality is inherent in our nature (a process discussed above), this process can indeed be studied and modified. Any interventions should be applied at the most basic level and as early as possible during individual human development. In addition, it allows for future technological developments which may help describe and manipulate the process.

A relevant notion here is that of a bifurcation. In mathematics, bifurcation theory describes how small changes in the parameter values of a certain system may result in a sudden change in the behaviour of that system. In other words, how a simple intervention at one point may cause the system to acquire new characteristics. I propose that there is a point during human development when the system changes direction and instead of following a path that leads to immortality (as discussed above), it follows the current direction of ageing and death, with preference for Darwinian evolution laws. Attempts at influencing the process of immortality should therefore directed at this exact bifurcation point, in order to force the system to follow a different path. One possible consideration is to see if the DNA can be manipulated in order for this to happen. I hereby propose two possible interventions. 

The first is based on transposons, which are segments of the DNA molecule that can influence certain genes. These ‘jumping genes’ are molecular elements (DNA sequences) that can move to different positions within the DNA. Transposons can cause mutations and genetic diseases, but also provide plasticity to the genome and contribute to the evolutions of genes, by creating new genes and protecting existing ones. Remember that mutations can not only be detrimental, but also beneficial to the organism. 

Over millions of years, many transposons have accumulated mutations and became inactive. It is now possible to re-activate some of these transposons using new technology. An example is the Sleeping Beauty (SB) transposon. This is a transposable element, member of the Tc1/mariner superfamily isolated from vertebrate DNA. These elements are parts of DNA that are currently inactive due to accumulation of mutations. The SB element was recently reactivated and found to continue being active in a variety of cells (both somatic and germ cells, in humans). It is relevant to the ELPIs theory because it confirms that even currently inactive genetic material can be activated and made to function efficiently. There are other transposons that have now been activated after millions of years of evolutionary inactivity. Examples are the piggyBac, Frog Prince, and Himar1 mariner transposon. These are currently used in human gene therapy.

The second intervention is based on Synthetic Biology, a new branch of Biology that combines a biological and technological approach to research. One example of such research is the manufacturing of artificial DNA which is then placed inside living cells, in order to influence their function.  This has already been achieved through, for example, the design of the repressilator, an artificially-designed genetic tool ( http://www.ncbi.nlm.nih.gov/pubmed/20866500). A targeted DNA approach may be one of the ways to stimulate mechanisms that protect against ageing, and promote extremely long lifespans. Biological and specifically genetic desired functions can be designed and implemented by using artificial means.

Relevant developments in Synthetic Biology could be the modulation of certain cancer repressor genes, or certain immortality promoting genes (already existing). These could then act perpetually in order to equalise the odds against early death by an ageing-related condition. Once the mechanism is in place it will operate spontaneously and continually in order to dramatically increase lifespan (see figure 1).

Both approaches (transposons and Synthetic Biology) can be used in order to modify stem cell function in a way that has never been possible in the past. It may be possible for example, to re-establish a viable production of stem cells and enrich the existing pool of uncommitted stem cells. For a discussion on stem cell supply, see:

http://anti-agingfirewalls.com/2010/11/07/closing-the-loop-in-the-stem-cell-supply-chain-%e2%80%93-presented-graphically/

Apart from future technological and scientific developments, another aim of ELPIs theory is to explore the possibility that there are certain interventions that can be used now in order to aid the achievement of indefinite lifespans, or in order to activate certain factors that are involved in HBI.

Two relevant concepts that are also interconnected are Hormesis and Stochastic Resonance, both of which may operate in a way to accelerate the changes needed for HBI.

Hormetic approaches can be directed at a variety of levels, such as nutritional, physical, sexual and pharmacological. This approach has been discussed in detail elsewhere (see the abstract here: (http://www.ncbi.nlm.nih.gov/pubmed/15929717) – contact me for the full text article). 

 A specific case of a hormetic approach is directed at cognition and encompasses Environmental Enrichment (EE) aided by technological inputs such as digital assistants (mobile internet, for example) in a context of societal and cultural progression. This is a novel approach to the issue of longevity, as it does not merely refer to achieving a healthy lifespan but also to actually force the existing model of human evolution to transit to a more sophisticated level. This is relevant because it indicates that despite the futuristic element in HBI, there could exist current interventions that can facilitate the process.

It could be suggested that the continual informational cognitive input may have a positive effect on epigenetic DNA changes which could then act in a way to up-regulate certain anti-ageing genes. This may be augmented by environmental enrichment, cultural and societal developments, and increased use of technology, such as digital assistants, nanotechnology and synthetic biology.

It is already known that the environment affects the DNA by causing epigenetic changes via DNA methyltransferases, histone acetylases, or methyltransferases, that could be either beneficial or detrimental  ( Carnero A, Lleonart ME Epigenetic mechanisms in senescence, immortalisation and cancer. Biol Rev Camb Philos Soc. 2010 Sep 16. doi: 10.1111/j.1469-185X.2010.00154.x. [Epub ahead of print] ). It has also been reported that maternal environment affects embryonic DNA (Dolinoy DC, Weinhouse C, Jones T, Rozek LS, Jirtle RL.Variable histone modifications at the A(vy) metastable epiallele. Epigenetics. 2010 Oct 4;5(7). [Epub ahead of print]). 

The fact that the environment (and thus EE) affects epigenetic mechanisms has been shown in many other recent studies, for example Haggarty P, et al. Human intelligence and polymorphisms in the DNA methyltransferase genes involved in epigenetic marking. PLoS One. 2010 Jun 25;5(6):e11329, and by Pozharny Y, et al. Epigenetics in women’s health care. Mt Sinai J Med. 2010 Mar;77(2):225-35. In another study  (Cohen Kadosh R, et al. Modulating Neuronal Activity Produces Specific and Long-Lasting Changes in Numerical Competence. Curr Biol. 2010 Nov 3. [Epub ahead of print])

it was shown that external brain stimulation has measurable effects on numerical ability, which supports the notion that other relevant (hormetic type) stimuli can have positive effects on cognition, thus forcing the system to transit, as in diagram 2. 

Apart from its effects on the brain, EE was also shown to positively affect vision, the retina, immunity, tissue repair, inflammatory response, and other physical parameters, thus having a holistic effect on the organism.  

Therefore it may be sensible to explore how Environmental Enrichment with technologically advanced means can have any effect on DNA expression and thus modulation of ageing-related genes. This can be aided from insights gained from Stochastic  Resonance. For example, it was shown (Söderlund GB, et al. The effects of background white noise on memory performance in inattentive school children. Behav Brain Funct. 2010 Sep 29;6:55)that input of noise (a hormetic event) influences dopamine-related internal noise and enhances the attention span of inattentive children. This suggests that suitably applied external stimulation can modify cognition/behaviour, thus giving credence to the suggestion that hormetic stimuli, if applied according to the rules of Stochastic Resonance may can have positive effects, via biochemically modulated brain mechanisms (in this case, dopamine).

Part 1. Science

SENS= Strategies for Engineered Negligible Senescence, and related areas. See www.sens.org

SB= Synthetic Biology. This includes any developments in artificially creating DNA, genes or other relevant molecules, as well as interventions using natural or artificial transposons, such as the Sleeping Beauty transposon. These may then help in improve stem cell actions. See: http://en.wikipedia.org/wiki/Synthetic_biology

Dynamical Systems= Mathematical exploration in order to discover, define and manipulate other relevant parameters or interventions. Includes notions from Stochastic Resonance, Bifurcation Theory and Non-linear Systems. See: http://en.wikipedia.org/wiki/Dynamical_systems_theory. For an example with regards to ageing see: http://www.ncbi.nlm.nih.gov/pubmed/12766532

Part 2. Public

AAM= Anti-Ageing Medicine, a broad term referring to therapies such as antioxidants, antiglycators and hormones, as well as more advanced therapies such as Calorie Restriction Mimetics, apoptotic modulators, TOR pathway modulators etc. For example, see: http://www.antiaging-systems.com/ARTICLE-615/introduction-to-antiaging-medicine.htm

Hormesis=Challenging external stimulations directed at multiple targets such as the sexual system, immunity, genes, metabolism, senses, social aspects. For relevant examples, see: http://www.ncbi.nlm.nih.gov/pubmed/20662589

Intellectual Complexity= Strategies for a continual intellectual stimulation and mental input, in association with cultural, technological and societal advances, in order to increase intellectual pressure upon the neural system and initiate suitable epigenetic changes. See discussion above.

Conclusions

It is suggested that human biological immortality is an intrinsic consequence of self-organisation in nature. In an attempt to accelerate this process I have formulated the ELPIs theory (see diagram 3) which endeavours to describe and modulate any relevant mechanisms and suggest interventions that can have a positive effect. One suggestion is the scientific study of how dynamical system theory can be applied in this respect. A suggestion that has relevance to the general public is the notion that hormesis, and specifically cognitive hormesis may be a possible tool for accelerating the gradual transition to indefinite lifespans.



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