Extreme Lifespans though Perpetual-Equalising Interventions
(Human Biological Immortality*)
* The term ‘Immortality’ in this discussion is only taken to mean ‘indefinite lifespans’, i.e. the elimination of involuntary death caused by ageing, and excludes any other meanings.
By Marios Kyriazis MD, Biomedical Gerontologist
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). During the course of discussing these ideas I adopt, on the whole, a post-positivist approach in that I accept that some elements of the discourse are generally conjectural rather than based upon solid scientific foundations. However I believe in the search for objective scientific truth, I recognise the value of experimental methodology and that of ontological realism, and follow Thomas Kuhn’s line of thinking. 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 towards more sophisticated stages, leading to the emergence of higher levels of complexity and novel coherent entities. Emergence has been described as a phenomenon whereby “…the properties, behaviours and functions of a living system and many of their constituent sub-systems, manifest themselves as inexplicably unpredicted novel properties, functions and behaviours, ones not observed in the system's subsystems and their components, and are not explainable or predictable from complete understanding the components' properties/functions/behaviours considered in isolation from the system that embeds them. (http://en.citizendium.org/wiki/Emergence_%28biology%29).
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 (2010) possible is encountered within human neural tissues i.e. human intelligence.
The universe started approximately 14 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 employ progressively quicker means, and so the slow process of evolution by natural selection will become gradually less relevant for 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, concluding perhaps within 50 years (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 to become members of a super-human, super-intelligent self-conscious system (Global Integration) – 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 evolutionary 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 involuntary 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. Note that, immortality is only taken to mean indefinite lifespans. Humans will still die by means other than ageing, such as illnesses, severe injuries or accidents. On average, it has been estimated that a life-span of 1700 years would be achievable if ageing was to be eliminated. Accidents and injuries will then limit the lifespan beyond that age, unless ways of overcoming involuntary death could be developed (such as consciousness uploading).
Metasystem Transitions
A Metasystem is the integration of a large number of systems that creates a novel level of complexity (an ‘emergence’). In the case below, a Metasystem is, in increasing order of magnitude, the DNA, the neuron, the brain and so on. Metasystem Transition(MT) is the transition from one Metasystem to another and is characteristic of evolution. Major (large-scale) Metasystem Transitions are also true paradigm shifts. Relevant MT are the transition from the DNA to the complexity of the neuron, and from the neurone to the brain. Recent MT include the transition from simple human cognition (brain) to social integration through communication, technology and ability to purposefully modulate our environment. The next MT is now occurring and involves the transition from social integration to global integration and transhumanism (i.e. a transition from evolution by natural selection to evolution by purposeful human effort). (Ref http://en.wikipedia.org/wiki/Transhumanism)
Interconnectivity and relationship between progressively higher levels of complexity with reference to humans
1. DNA 2. Neuron 3. Brain 4. Society 5. Global Integration
(Trans-humanism)
(For the sake of completeness, I will mention that there is a final(?) level 6 which is Universal integration and concerns the integration of all intelligent life in the universe in the sense that the entire universe becomes a super-cognitive, unified entity. However, as this is highly speculative and does not have immediate relevance to human immortality, it will not be discussed. Its only relevance for the purposes of this discussion is to show that levels 5 is a necessary prerequisite for continuing evolution and if there is a need to reach level 6, then level 5 must be achieved (thus immortality must ensue).
Each level is characterised by information and energy transfer. Each level is incorporated in a self-sustaining feedback loop and influences not only each of the next levels but also each of the previous ones, by long-range inter-level reciprocal causality (Walsh DM, Organisms as natural purposes: the contemporary evolutionary perspective. Stud Hist Philos Biol Biomed Sci 2006; 37: 771-91). The integration of signals occurs across multiple time scales and these signals display a dynamic downward causation. These living systems operate within a context that depends on the environment, which in turn affects the properties of this system. It is known for example that the environment has an indirect effect on genes via epigenetic changes (Zurek WJ (ed) 1991 Complexity, Entropy, and the Physics of Information: The Proceedings of the Workshop on the Complexity, Entropy, and the Physics of Information, Santa Fe, New Mexico. Addison-Wesley Publishing Company, The Advanced Book Program, Redwood City) which indicates that level 1 is indirectly influenced by level 4 in the example above.
This discussion is important because it provides insights into how the process of emergence of level 5 can be facilitated.
Emergence within a set of systems (Retrieved from http://en.citizendium.org/wiki/Emergence_%28biology%29) is characterised by four necessary elements (in bold) (Hazen RM (2005) Genesis: The Scientific Quest for Life's Origin. Joseph Henry Press, Washington DC. ISBN 0309094321)
A. A suitable concentration of elements within a system and an increasing complexity which each subsequent level. It is clear that in the above system transition, the concentration of all elements is now sufficiently large, and that the complexity increases with each level. Level 5 is now emerging.
B. The interconnections between the components of each level must be sufficiently complex with varied types of connections. The connectivity of each level is well established. There is a need to study how level 4 facilitates the emergence of level 5 and how this, in turn, influence preceding levels. Also the fractal geometry of each level is characteristic and discussed below.
C. The flow of energy and information through the system must be free and of sufficient magnitude. The flow of information from DNA, to neurons, to brains to societies AND BACK with each level is well recognised. These then influence the emergence and consolidation of level 5. There are well-defined input thresholds that characterise each transition and modulation of signalling in response to transient stimulation by both preceding and forward levels. These inputs thresholds can be influenced via stochastic resonance interventions (see below).
D. The flow of energy through the system must be in a regular cyclic manner in order to facilitate its spatiotemporal patterns. This means that in order to consolidate level 5 it is necessary to apply energy in a cyclical manner. Energy (in the form of information) from level 4 is applied upon level 5 and then returns to level 4 and preceding levels. The very presence of level 4 will, if the input of information is optimal, eventually cause the transition to level 5.
So this shows that in order to facilitate the emergence of level 5 (global integration and thus indefinite lifespans) all of the above four requirements must be facilitated with each step. Particularly, with reference to C and D above, this can be accelerated and augmented via an enriched, hormetic and goal-seeking environment. For example, the behaviour of a human neuron does not only depend on its own physiological status but also on its environment, i.e. all the biological and other properties of the brain (Thompson E, Varela FJ. Radical embodiment: neural dynamics and consciousness. Trends Cogn Sci. 2001;5(10):418-425). In turn, the function of the brain influences individual neurons (for example by physical confinement and via cell-to-cell signaling). In addition, the brain also responds to its environment, namely the individual body that it lives in and consequently to the society that the individual body lives in. The society reciprocally influences the brain via conventions, restrictions and opportunities, and thus it also affect the neuron indirectly, which affects its own DNA. Information from one level freely flows and enhances all the others.
Fractal geometry
The complex and dynamical nature of the individual components of the model (1-4, and perhaps 5) is manifested in the underlying sophisticated geometry with power- law properties, which can be described in terms of objects with fractal dimension.
The fractal dimension of the DNA has been described (for example, Cattani C. Fractals and Hidden Symmetries in DNA. Mathematical Problems in Engineering Volume 20100 who have discussed the geometrical rules that describe the distribution of nucleotides along the DNA molecule and described that the DNA is characterized by DNA walks with fractal shape. With regards to the neuron it has been proposed that Euclidean geometry is not suitable for a geometrical interpretation of its structural and functional properties, at least in humans (Pellionisz AJ. Neural geometry: towards a fractal model of neurons. Cambridge University Press, 1989), and neural fractal properties are widely manifest. In addition, the fractal properties of the brain as a whole have been described by several researchers. See for example, a full discussion here: http://www.dhushara.com/book/paps/chaos/bchaos1.htm. Finally, one level up from the level of individual brain, is the level of society integration. The dynamic, continual processes that characterise societal interactions operate within an integrating field and have properties that are describable by fractal geometry (Harle R. Chaos, archetypes, and the all-integrating field. Nonlinear Dynamics Psychol Life Sci. 2010;14(1):101-15).
Part 2. Accelerating the process
If it is assumed that the above discussion is, on the whole, valid, 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 leading to 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 in this respect.
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. It is important to 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. More details regarding the repressilator are available here 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.
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/
Aside 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). Hormesis is believed to have epigenetic adaptive relevance by modulating DNA methylation, remodelling chromatin and by silencing microRNA-regulated transcription (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836156/).
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.
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. This is a positive notion, as it shows that external stimulation does not only ‘rejuvenates’ the brain but also other non-neural structures and mechanisms needed against ageing.
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).
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
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.
Further Details on Environmental Enrichment (EE)
As mentioned above, it may be possible to accelerate the input of complex, abstract and novel information into the human brain by using insights derived from EE research.
EE stimulates the information processing abilities of the brain. The information is gathered not only via sensory mechanisms but also by elements within the social and cultural environment of the subject. The opposite effect, i.e. environmental deprivation has been shown to be negatively correlated with cognitive development. EE in this wide context is taken to include any cognitive stimulation or challenge, cerebral inputs following exposure to novel and innovative environments, societal interactions, cultural inputs, stimulation based upon interactions with technology (meaningful use of internet, digital assistants and other silicon-based technology), positive thinking (i.e. internally created stimulation), cognitive or intellectual achievement, avoidance of routine and boredom, and stimulation or challenges via unconventional channels (sexual, mechanical, chemical etc).
Further, in a wider philosophical context EE also includes more abstract concepts such as a search for virtue and wisdom, the pursuit of excellence and brilliance, increased goal-seeking behaviour, and eschewal of mediocrity. In particular reference to philosophy, it may be possible to gain some clearer understanding by re-examining the Stoic philosophical school of thought. This shares several ideas with modern attempts at prolonging human lifespan. The Stoics believed in a non-dualistic, deterministic paradigm, where logic and reason formed part of their everyday life. The aim was to attain virtue, taken to mean human excellence. The ELPIs model is based on a deterministic, non-dualistic approach, described by the laws of Chaos theory (dynamical systems) and suggests that, in order to accelerate the natural transition from human evolution by natural selection to a post-Darwinian domain (where indefinite lifespans are the norm), it is necessary to lead a life of constant intellectual stimulation, innovation and avoidance of routine, as outlined above. The search for intellectual excellence increases neural inputs which effect epigenetic changes that can up-regulate age repair mechanisms (see http://www.liebertonline.com/doi/abs/10.1089/rej.2005.8.96?journalCode=rej and http://www.liebertonline.com/doi/abs/10.1089/rej.2009.0996 ). Thus it is possible to conciliate the Stoic ideas with the processes that lead to both technological and developmental Singularities, using approaches that transcend time and are deeply embedded in human nature.
The basic structural effects of EE upon the brain have been described elsewhere. In short, EE increases the number of synapses and synaptic activation, dendrite complexity, glial cell number and volume, capillary width, neurogenesis (also in adults), and reduces the impact of brain injury, dementia, brain infarct and brain ageing.
Here I will attempt to outline the effects EE has upon tissues other than neural, in an effort to show that EE in the wider sense (stimulation, challenge, novelty, avoidance of routine and mediocrity) may have beneficial effects on the organism as a whole. It is also worth remembering that EE works on a favourable substrate, i.e. on biological processes that have an intrinsic propensity to achieve higher complexity and thus longer lifespans, therefore the entropy increases are minimal.
EE enhances the plasticity of visual function and it has been shown to improve amblyopia by causing epigenetic chromatin changes (Baroncelli L, Braschi C, Spolidoro M, Begenisic T, Sale A, Maffei L.Nurturing brain plasticity: impact of environmental enrichment. Cell Death Differ. 2010;17(7):1092-103). In laboratory animals EE was shown to have a postnatal effect that was dependant upon maternal care behaviour, and that resulted in improvement of visual acuity (Sale A, Putignano E, Cancedda L, Landi S, Cirulli F, Berardi N, Maffei L Enriched environment and acceleration of visual system development. Neuropharmacology. 2004 ;47(5):649-60.) Kiss et al. (Kiss P, Atlasz T, Szabadfi K, Horvath G, Griecs M, Farkas J, Matkovits A, Toth G, Lubics A, Tamas A, Gabriel R, Reglodi D. Comparison between PACAP- and enriched environment-induced retinal protection in MSG-treated newborn rats. Neurosci Lett. 2010 Nov 2. [Epub ahead of print]) have demonstrated that EE can afford significant neuroprotection in retinal degeneration in animals.
Behavioural and environmental enrichment in dogs was shown to significantly increase phagocytosis (Dietary antioxidants and behavioral enrichment enhance neutrophil phagocytosis in geriatric Beagles. Vet Immunol Immunopathol. 2006 Sep 15;113(1-2):224-33), whereas macrophage chemotaxis, lymphocyte proliferation and natural killer cell activity increased and oxidative damage stress decreased in animals exposed to EE. These effects were more pronounced in older animals (Arranz L, De Castro NM, Baeza I, Maté I, Viveros MP, De la Fuente M.Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice. Rejuvenation Res. 2010 ;13(4):415-28).
Rewarding EE is known to increase IgG, T-cell proliferation and overall wound repair (Ernst K, Tuchscherer M, Kanitz E, Puppe B, Manteuffel G. Effects of attention and rewarded activity on immune parameters and wound healing in pigs. Physiol Behav. 2006;89(3):448-56). It is believed that external influences such as the degree of mental stress, physical activity and a generally stimulating environment are sensed by neurones (particularly in the dentate gyrus of the hippocampus), and trigger adult neurogenesis and epigenetic plasticity of the DNA (Schaeffer EL, Novaes BA, da Silva ER, Skaf HD, Mendes-Neto AG. Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain. Prog Neuropsychopharmacol Biol Psychiatry. 2009 ;33(7):1087-102). The epigenetic basis is a dynamic and reversible DNA methylation process (Covic M, Karaca E, Lie DC. Epigenetic regulation of neurogenesis in the adult hippocampus. Heredity. 2010 ;105(1):122-34).
This shows how external stimulation, directly affects epigenomics.
Long-term cognitive enhancement via stimulating environment can affect mRNA expression in cerebral receptors and thus causes modification of gene expression (Kalbe C, Puppe B. Long-term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs. Genes Brain Behav. 2010; 9(1):75-83). The fact that EE effects epigenetic changes has been shown by several researchers (Rampon C, Jiang CH, Dong H, Lockhart DJ, Hu Y. Effects of environmental enrichment on gene expression in the brain Proc Natl Acad Sci U S A. 2000; 97(23): 12880–12884).
EE reduces formation of amyloid beta, and improves neurovascular function and behavioural symptoms in mice with Alzheimer-like disease. It also attenuates pro-oxidant activity and up-regulates anti-oxidant defences. In addition it down-regulates inflammatory responses and caspases (thus reducing apoptosis)( Herring A, Blome M, Ambrée O, Sachser N, Paulus W, Keyvani K. Reduction of cerebral oxidative stress following environmental enrichment in mice with Alzheimer-like pathology. Brain Pathol. 2010; 20(1):166-75. This is important because it suggests that EE can affect systemic processes (such as oxidation, apoptosis and inflammation) that are involved in ageing, and not only brain structures.
The effects of EE have been investigated in relation to anxiety and stress. It was found that EE increases physical activity, reduces anxiety behaviour, improved ability to deal with stress and an increased activity of NK cells (Benaroya-Milshtein N, Hollander N, Apter A, Kukulansky T, Raz N, Wilf A, Yaniv I, Pick CG. Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity. Eur J Neurosci. 2004;20(5):1341-7).
The beneficial effects of EE on immunomodulation are enhanced by nutritional factors (antioxidant ingestion) and physical exercise (De la Fuente M, Gimenez-Llort L. Models of aging of neuroimmunomodulation: strategies for its improvement. Neuroimmunomodulation. 2010;17(3):213-6).
A type of EE is noise stimulation. Background random noise can be enhanced via stochastic resonance processes in order to have physical effects. Example( Wells C, Ward LM, Chua R, Timothy Inglis J. Touch noise increases vibrotactile sensitivity in old and young. Psychol Sci. 2005;16(4):313-20), and (Söderlund GB, Sikström S, Loftesnes JM, Sonuga-Barke EJ.The effects of background white noise on memory performance in inattentive school children. Behav Brain Funct. 2010;6:55). Thiriet at al. (Thiriet N, Amar L, Toussay X, Lardeux V, Ladenheim B. Environmental enrichment during adolescence regulates gene expression in the striatum of mice Brain Res. 200; 1222: 31–41) reported that mice exposed to EE show several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and metabolism.
In all, it is shown how increased cognitive input causes DNA modifications that help develop brain and societal complexity (and thus aids in the process of global integration).
However, the danger exists that overstimulation may cause deleterious results. As Kiss et al. remark (Kiss HJ, Mihalik A, Nastasi T, Ory B. Ageing as a price of cooperation and complexity: self-organisation of complex systems causes the gradual deterioration of constituent networks. Bioessays 2009; (6):651-664):
“…A stable environment leads to over-optimization and forms an ‘always-old’ network which accumulates damage. A rapidly changing environment develops competition, forming a ‘forever-young’ network which may suffer an occasional over-perturbation, exhausting system resources”.
It is therefore important to study optimization strategies, in order to avoid over-exposure to a stimulus.
Conclusions
The transition from evolution by natural selection to a post-Darwinian domain is one of the most important transitions in biology, and unique in human history. We are beginning to witness a true Kuhnian paradigm shift, a change in fundamental sets of beliefs and assumptions about human evolution. The anomaly of death by ageing cannot be explained by modern emerging scientific doctrines (singularities, self-organised criticalities, hierarchically emergent complex neural, digital, technological and societal structures). The new paradigm may explain why, in order for further evolution of human intellectual sophistication, it is necessary for humans to remain alive for centuries instead of being killed prematurely by ageing.
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 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.