Sunday 30 December 2012

Environmental Enrichment - Practical Steps Towards Indefinite Lifespans


NB: It is important to consider this paper within the framework of a ‘Conceptual Model Leading to Indefinite Lifespans’, and not in isolation

Many of us expect and demand to live in a world where the ageing process has been eliminated. And yet, which trivial exceptions, there are very few practical actions we can implement today in order to deal with this issue. I am not referring to a generally healthy lifestyle and my intention is not merely to live a healthy life until the age of 100. My intention is to break through the barrier of the current maximum human lifespan and, having eliminated the increased death rate associated with age, live for a period without any pre-determined limits. At the same time, I also wish to suggest practical, relevant to everyday life, yet scientifically rigorous steps which may be relevant, in their embryonic form, in promoting radical life extension well beyond the current limits.

Elsewhere (http://ieet.org/index.php/IEET/more/kyriazis20121031) I argued that devising pharmacological treatments directed at individuals alone may not be a sufficient strategy to eradicate ageing. These simplistic treatments or therapies are based, in my view, upon a reductionistic argument, which lacks sophistication and evolutionary robustness.

I consider ageing not as a disease that needs to be cured with drugs, but as a process encountered in nature (but not a natural process) that happens by default, due to evolutionary constraints. These constraints, namely the insufficient amount of energy allocated to somatic repair at the benefit of germ-line immortality, are not immutable, nor are they necessary.

In order to accelerate the process that leads to radical life extension it may be possible to start considering activities and strategies that have practical relevance to anyone alive today, without the need to wait for new putative pharmacological therapies that can ‘cure’ ageing. These practical strategies include hormetic environmental enrichment, societal and planetary engagement, and a power law lifestyle. The intention of the activities is to constantly increase neuronal demand for energy (via a continual input of meaningful, actionable and high-quality information), so that to induce an evolutional phase transition (http://en.wikipedia.org/wiki/Phase_transition) that favours somatic cell repair.   In other words, the high-quality information overload will require appropriate action by the organism, action which will eventually be translated into increased efficiency of somatic repair mechanisms

a. Hormetic Environmental Enrichment

Hormesis is a universal phenomenon characterised by a ‘low-dose stimulation, high-dose inhibition’ dogma. In practical terms, a hormetic challenge engages the organism to appropriately respond by up-regulating its repairs mechanisms.  An environment where there is a sufficient number of challenges or stimuli is associated with a general up-regulation of neural, hormonal, immune or other parameters which lead to improved health. This is not merely a local, limited scope phenomenon. Its validity is global and has benefits which have not been realised even by proponents of the hormesis theory. A hormetically-enriched environment is one that gives the opportunity for a correct choice to be made from a list of available options. In order for the process to be successful, it is necessary to inhabit an environment which offers a number of options. An environment in which there is an enhanced goal-seeking behaviour falling outside one’s ‘comfort zone’, is an ideal such setting.

It may be possible to use hormesis and environmental enrichment in order to improve our immune system by employing strategies that utilise an appropriate degree of positive stress. Based on this principle I am suggesting that we need to expose our immune system to a variety of mild, repeated challenges, in order to trigger suitable beneficial immune parameters and strengthen our immune response.

For example, we need to eschew total cleaningness. Being excessively clean to the point of sterilisation does not allow our immune system any room for growth and development because the exposure to bacteria, viruses or toxins becomes minimised. I am suggesting to avoid complete and ritual cleansing, and to expand our opportunities of coming into contact with raw nature. By this I mean moderate exposure to dirt, wind, sun, and mild natural environmental dangers (mosquito bites, insect bites, scratches, minor injuries, cold, heat etc.). One practical suggestion which may be beneficial include bare-hand gardening. Any grazes or scratches will stimulate the immune system and increase its effectiveness at fighting infections and healing of more serious wounds at a later stage. Another example is to allow yourself to experience the sensation of the wind or direct sunshine upon your naked skin. This may be done any time in the garden or even at a nudist environment. Research shows that the sensors on the skin can detect the sensation of the wind and transmit the information to the brain which, in turn, activates compounds and agents that can repair skin damage, restore any changes in temperature, and heal skin irritation. Through this activity the neuro-immune mechanisms remain activated and are ready to respond to a more serious challenge. In this respect, research has shown that exposure to mild wind and light rain improves the immune system of laboratory animals, and increases their ability to cope in a much colder or wetter environment in the future.  In addition, exposure to mild (hormetic) UV radiation has been shown to modulate apoptosis and prevent unnecessary death of healthy cells, and at the same time promote elimination of cancerous cells.

Exposure to very low temperatures (cryotherapy) is known to improve blood circulation, stimulate immunity and help in several chronic degenerative conditions such as arthritis and hypertension. The basis is a hormetic response, a brief exposure to a damaging agent (in this cases extreme cold) that forces the body to respond and prepares it for a more serious or sustained subsequent danger. Specifically, exposure to short bursts of cold stress has been proven to increase the function of macrophages, whereas a more prolonged exposure diminishes their function. This is a typical example of hormesis when a short-lived challenge is beneficial, but becomes detrimental if it is more prolonged.

A more unusual or unconventional way of experiencing a challenging environment is extreme fairground rides (exposure to hyper-gravity is a well-known method for achieving hormesis in the laboratory). Sauna (exposure to high temperature) has also been suggested as having a hormetic effect. Low dose ionising radiation, which activates DNA repair and protects against cancer and other degeneration is a promising but impractical hormetic stimulation, awaiting clarification.

Even sexual environmental enrichment, which can be applied for the purposeful up-regulation of sexual parameters can be employed as a longevity strategy. Examples of hormetic enrichment are vibrotactile stimulation, visual eroticism, and sexual fantasies. These activities increase muscular, skeletal, visual, olfactory and other inputs into the brain, which activate biochemical pathways not only within the brain itself but elsewhere in the body. The stimulation up-regulates several hormones and factors such as oxytocin, endorphins, testosterone, oestrogens, DHEA (dehydroepiandrostenone) and BDNF (brain derived neurotrophic factor). These, in turn, enhance well-being, immunity defences, and antioxidant mechanisms, to name a few. It has been shown that the activity of oxytocin is increased during novel sexual experiences, and this has a positive effect on neuron dendrite remodelling, resulting in an improved social cognition and communication. It is also known that an enriched environment can enhance sexuality and mating patterns, as well as promote better interest and exploratory patterns in animals. Finally, a hormetically-enriched environment leads to a sustained elevation of testosterone, a reduction in free radical damage and thus an improvement in immune function.

In summary, exposure to light, repeated physical challenges can reinforce the immune system and maintain it in a condition in readiness to fight more serious or life threatening conditions, including age-related degeneration. The way to choose whether a stimulus is sufficient or not, is to refer to the notion of ‘challenge versus threat’. If we have the ability to deal with a problem then this is a (hormetic) ‘challenge’. If we don’t have the resources to deal with it, then it is a ‘threat’, i.e. damaging, and should be avoided.

 

b. Societal and Planetary Engagement

I argued elsewhere about the necessity to build societies that enhance and promote radical human life extension. As natural evolution tends to promote survival of a fit organism, (fitness within a particular niche) we find ourselves trying to survive in a niche of increasing technological engagement and sophistication. In order to enhance our fitness within this environment we need to integrate fully within the technological society and within the planet in general. As examples of this I suggested (http://hplusmagazine.com/2012/12/06/the-longevity-of-real-human-avatars/) that we need to increase the number of our connections both in virtual and in real terms, and increase the unity of our connections, such as using only one (user)name for all environments across all platforms. Finally we need to increase the strength of our connections. We should provide as much information about ourselves as possible, and join as many online information-sharing facilities as practicable.

These activities increases the value of incoming information into the brain which, in trying to assimilate it, produces neurotrophic factors and neuro-protecting substances that repair coincidental age-related damage.

 

c. Power Law Lifestyle

Ageing is a universal phenomenon and it obeys universal laws. Certain mathematical principles that apply globally can thus be applied in ageing. One of these laws concerns the application of power law and fractals.  Power law is a mathematical relationship between two quantities. In the case of ageing, I consider the relationship that exists between the frequency of any activity as a power of its intensity. In practice, this means that in order to follow a more natural and therefore evolutionarily successful lifestyle, the frequency of any given activity (such as exercise for instance) needs to vary as a power of its intensity: frequent low-intensity exercises, less frequent medium-intensity exercises, and rare high-intensity ones. A good example of power law lifestyle is encountered in the Paleolithic concept. The modern notion of the Paleolithic lifestyle refers to a lifestyle that exposes us to situations similar to those experienced by humans living in the wild, natural environment over 10 000 years ago. The notion refers to both the nutritional and physical challenges (Paleo diet and the Paleo lifestyle), and is based upon the concepts of hormesis and power law.

The Paleo diet umbrella encompasses two important nutritional concepts, that of calorie restriction and that of intermittent fasting. Calorie restriction is as a form of nutritional hormesis. Another possible way for achieving positive nutritional stress is through Intermittent Fasting which is based on the ‘feast or famine’ pattern normally encountered in the wild. The practice places the organism under nutritional stress, which can be beneficial if it is not prolonged. Benefits include an improvement in blood sugar and cholesterol levels, protection against brain cell toxicity, strengthening of the immune system and many others.

An important section of a Paleo lifestyle is exercise. With hormesis in mind, I recommend physical activity that has power law characteristics, meaning that we need to follow an exercise regime including many low-level exercises, some moderate ones and very few intense activities. These physical exercises need to be performed at irregular intervals and durations for the full hormetic effect to become apparent.

Examples are low level running or walking, some swimming, simple climbing or scrambling, hanging from branches and climbing trees, jumping or leaping from rocks and similar. Other Paleo exercises include carrying and moving heavy weight (rocks, tree trunks), barefoot walking or running, walking through thick forest or undergrowth, running in water (in a swallow sea or a lake, for example). At infrequent intervals do some extreme exercises such as full sprinting. Avoid any regular exercise in a gym. These activities improve the sense of balance, strengthen the bones against osteoporosis, improve immunity and exercise diverse groups of muscles. A very good and relevant concept with regards to hormetic, power-law exercise is that of MoveNat (see www.movenat.com  for videos and examples of exercise).

Apart from physical exercise, a relevant issue here is that of hormetic brain stimulation including stimulation of the senses. This involves challenging your brain with unusual puzzles, mind games or cognitive situations, and I have discussed many examples of such exercises many times in the past. The main message of a hormetic Paleo lifestyle is that all activities must follow an irregular, uncommon and non-monotonic pattern, in a way that mimics the challenges our ancestors have encountered in the wild. This places a modern lifestyle within a situation with deeper biological significance.

Conclusion

In the (near) future there may well be therapies and treatments based on stem cells, telomerase, nanotechnology etc., which will be available to the wider public for use as anti-ageing therapies. In my opinion this will not happen for another several decades, and it will not be an effective or complete radical life extension approach either. In the meantime, I offer a novel approach that may have an impact on natural evolutionary processes, which lead to indefinite lifespans (see my other publications and blogs). These approaches have practical significance now, and are available to anyone, without the need to wait for any future artificial treatments.  There is no point in considering these activities in isolation. It is the totality of these strategies which is based on a reciprocally-influencing principle that matters. The activities have a direct anatomical and biological impact upon hormonal, immune, neuronal and other processes that are valuable in repairing and preventing age-related damage. In addition, the practice as a whole is aided by natural evolutionary processes that enhance fitness and survival within a technological niche. This is not going to afford extreme lifespans overnight but it is a step in the right direction. Unfortunately, it is predicted that, in order for the process to be successful, it is not a matter of how well an individual is enriched but also a matter of how many enriched individuals exist. In other words the achievement of radical life extension depends on the interconnectedness of a critical number of many enhanced individuals.

Tuesday 24 January 2012

Bio-Philosophical Arguments for Human Biological Immortality

When you eliminate the reason for ageing, there will be no reason that denies ’non-ageing’.
Ageing does not happen by default – it only happens because there is a deep-rooted underlying reason. When this reason is eliminated, there would be no reason why ageing needs to continue.  
The reason for ageing has been known for some time. Ultimately, ageing happens due to a discrepancy between the rate of biological damage and the rate of repair. The rate of biological repair mechanisms tends to become progressively compromised as a function of age, resulting in accumulation of damaged biological material that reduces useful function. The underlying cause of this is lack of energy resources - these are being diverted, by Darwinian forces, from the somatic repair to the repair of the germ-line. Any intentional attempt which improves the input of potential energy into an organic system makes the equalisation of the rate of damage vs repair more likely, and thus ultimately must result in retardation of ageing [ageing equals loss of energy and thus loss of complexity. Non-ageing is virtually stable energy and thus higher complexity].  In this case, the reason for ageing is essentially removed. If there is no reason why ageing must happen, then it will not happen.

Biology ‘Constructs’- Physics ‘ Destruct ’

Or:
Energy is a medium used by Biology in order to thwart Physics
Entropy is a medium used by Physics in order to thwart Biology

(Here, I deliberately take an animistic stance, attributing human-like characteristics to inanimate patterns. I use notions based on action ontology in order to make my ideas easier to understand)

Biology has a general tendency to advance from simple to complex, whereas Physics have an opposite tendency, from complex to simple. In other words, biology is likely to increase potential energy, biological sophistication and redundancy (an Intentional Stance, see Dennett   http://en.wikipedia.org/wiki/Intentional_stance), whereas Physical laws seek a state of lowest energy, minimal uncertainty and minimal entropy (the Intentional Stance with regards to Physics is the tendency towards minimum potential energy).
In this context, the term Physics refers to classical Physics (friction, gravity, tension etc.) and thermodynamics, rather than to all branches of Physics such as relativity or quantum theories. Of course, I acknowledge that Physical theories are merely descriptions of what we observe empirically, and are not describing definitive reality.
Therefore, it can be said that Biology and Physics are entangled in an eternal confrontation, each leaning towards its own respective ‘aims’, but maintaining an overall balance, resulting in life with predefined limits, (i.e. a human lifespan of 80-120 years). In order to influence this balance (and increase our odds of living well beyond this limit) we need to reduce the impact of physical laws and/or strengthen our biological assets.  
As it is hitherto impossible to change the laws of Physics*, one way to tip the balance in our favour is to enhance the laws of Biology.
* Nevertheless, the laws of Physics are not as immutable as we think, being just representations of our observations. Ultimate reality may be different from observed reality.
NB. According to Eric Chaisson (www.esalenctr.org/display/confpage.cfm?confid=10&pageid=102&pgtype=1), the expansion of the universe (a process described by Physics), is responsible for the rise of complexity in biological and other systems. As the universe expands, it makes energy easily available for use by any system (including a biological and thus a human) in order to increase its complexity. Complexity declines with age and this is due to the accumulation of damage that it is not repaired because of limited energy resources. Any process that increases available energy would be able to reverse this decline and so ageing will slow down or virtually stop. Therefore, it appears that Physical laws if applied in a suitable manner may ultimately enhance Biology.  
In Chaisson’s opinion, Darwinian evolution is only a small subset within a wider Cosmic Evolutionary framework, and it could be possible that Darwinian evolution will be superseded by other, more effective forms of evolution.
Evolution by natural selection is the main obstacle to defeating ageing and thus bars HBI (Human Biological Immortality), because it requires the survival of the germ-line and thus diverts resources from somatic repair. If/when evolution by natural selection begins to weaken, the restriction of energy resources upon the soma will be eased, the soma will have improved resources for its repairs and thus it will live longer.
Based on the assumption that Biology tends to progress ‘from simple to complex’  it is reasonable to suggest that, if there is a way that increases biological complexity or sophistication, then this would have an impact upon health/longevity (because it will enhance biological assets and allow biology to continue its tendency for increased complexity).
I believe that ageing is due to loss of complexity of biological systems (increased entropy over time). In order to counteract this, we must input more energy into the system in the form of cognitive stimulation, i.e.  informational energy, which activates many biological processes. This has been proven in many experiments.
During everyday life we are exposed to random unintentional challenges and stimulation (cognitive challenges, novelty of the environment, new ideas and situations). This helps our brain function well. Against this, we lose energy (increasing entropy), which eventually causes death because the degree of information input tends to zero with time, whereas entropy tends to infinity.
I propose to introduce another variable, the sum of intentional cognitive stimulation (i.e. intentional stimulation, special brain exercises, sense exercises, goal-oriented behaviour, seeking novelty and excellence etc.)  which  adds  robustness into the equation.  If entropy increases with age (obeying physical laws), this will have no meaningful impact because we can increase the amount of intentional brain stimulation.

This model accommodates the concept of Free Energy Rate Density (FERD) roughly the degree of density of energy flowing through a unit space of a system. The higher the FERD, the higher the complexity and intelligence of a system. For example, the Sun has 4 ergs per second per cubic cm, whereas the human brain has 150,000 ergs per second per cubic cm. This means that the Sun, despite its enormous reserves of energy, is considerably dumber than a human brain. This supports the view that energy must be maintained high in order to maintain intelligence (something biology does naturally for us), and when complexity declines due to physical constrains, we need to try and increase it by increasing FERD parameters.
Therefore, there is a need to reach an optimum between intentional increase of neuro-cognitive stimulation, against the increase of entropy, in order to achieve long life. The more we keep this system going, the longer the lifespan.

Remember that intelligence is ultimately the ability to make consistently correct selections from available choices. This means that one has to be in a position that contains (is forced to contain) challenges that need resolving, and choices that need to be made. Routine, monotony and regularity do not account for increased need to select, whereas variability, irregularity and uncertainty maximise our need to select (and thus increase intelligence) and thus increase informational energy.
The assumption is that there is an upwards ‘endeavour’ aiming to increase complexity, sophistication and intelligence, with the highest step being that of pure global intelligence (spirit).
Metaphysical contexts
In metaphysical terms, "spirit" has acquired a number of meanings. One of these is :
1 .An incorporeal but ubiquitous, non-quantifiable substance or energy present individually in all living things. Unlike the concept of souls (often regarded as eternal and sometimes believed to pre-exist the body) a spirit develops and grows as an integral aspect of a living (see Wikipedia).
I am suggesting that it is possible to work towards this stage by intentionally increasing external inputs, AND by optimising and enhancing the usage of internal cognitive signals.
This touches on the religious, i.e. the search for higher, pure metaphysical states, via meditation and religious rituals/practices. It also touches on the philosophical, with the search for excellence. Both the religious search for spiritual purity and the philosophical search for excellence, are merely disciplined and intentional enhancements of external cognitive information and maximal use of internal cognitive powers (meditation, mental discipline).
In the biological realm, this translates to a search for higher intelligence (here intelligence is defined as an ability to repeatedly make appropriate selections from a list of available options). For this there is a need to optimize the use of information by the brain, i.e. to make informational inputs use metabolic energy optimally.
It is necessary to work stepwise: first increase external cognitive inputs, then use these in an optimal way to work towards achieving more abstract stages such as excellence and awe (Kazantzakis calls this ‘Holy Terror’, the highest point of human mind can achieve).

What constitutes a good stimulation or challenge
A Positive Challenge is a condition that requires action (see F. Heylighen) because it represents an opportunity to be exploited. These can be planned/anticipated or unexpected/unintended. My advice is to follow a program of planned positive challenges. This is essentially a problem that needs resolving, and the brain is forced to make a decision one way or the other. It is forced to SELECT the best option among a number of others. A suitable/appropriate selection itself creates information (Shannon’s reduction of uncertainty).  Meaningful Information (knowledge, experience, wisdom, excellence), via expressive activation of appropriate brain mechanisms (sensory to cortex and other areas) activates (increases the energy available to, or the potential energy of) biological patterns and agents that then improve repair and maintenance, thus non-ageing.
In this respect, challenge (accumulation of useful information) can prevent regress, i.e. reduce the rate of entropy increase. According to Shannon, entropy increase is associated with loss of information, so more information equals a reduced rate of loss of thermodynamical energy. Increased entropy destroys organisation.
However not all information is useful, and not a lot of information is beneficial, so it is necessary to filter it in order to avoid information overload.  Suitable information is necessary in order to improve problem solving (by our biological processes). This will be achieved if the biological process can make the appropriate selection when confronted with a challenge. The increased power of selection means that the best choices will be chosen for the ultimate benefit of the organism.
The information must be analyzed and judged by an active process, and not just accumulated in a disorganized manner.
It has been shown in some experiments that information can be transformed into energy (Experimental demonstration of information-to-energy conversion and validation of the generalised jarzynski equality. A Toyabe et al. Nature Physics vol 6  p988-992, 2010). Also, the informational transfer process is associated with decrease entropy (Coherent informational energy and entropy. A. Avramescu J Documentation 1993 36(4)293).

The benefits of challenge are derived not only from external information but also from internally created abstract thoughts, meditation, awe etc. Intentional cognitive enhancement should be distinguished from a mere passive cognitive stimulation.

The generation of entropy over an average lifespan (around 80 years) was found to be in the region of 11,404kJ/K (Degrees kelvin) (Silva AC,  Annamala K. Entropy Generation and Human Aging: Lifespan Entropy and Effect of Physical Activity Levels. Entropy 2008, 10;100-123). No entropy generation equals death.

Any reduction in the entropy production would therefore result/be associated with an increased lifespan (longer dt). Also, any increase of meaningful energy into the system would have the same result.


How to choose an ideal degree of challenge
Here, consider Csikszentmihalyi's concept of ‘flow’. Essentially, the concept describes how a challenge that matches one’s skills and abilities causes well-being. If the challenge is over one’s ability then it causes anxiety. If it is below, it causes boredom (see equation above where the values of Ai are above or below k). This is similar to Blascovich's ideas of ‘challenge versus threat’. A challenge is a situation that matches your resources to deal with it. A threat is when your resources are below what is necessary to deal with it (causing anxiety). So, if a mental challenge causes excessive stress or anxiety, is unlikely to be beneficial in ageing. If it is of such a low intensity that causes boredom, then it will not be beneficial either.
It has been suggested that the frequency, duration, type and level of the challenge has a power law distribution (see Le Corre), meaning that low intensity and frequent challenges must be occasionally enriched with infrequent high intensity ones.
According to Le Corre (http://movnat.com/movnat-team/erwan-le-corre-founder-and-master-instructor-2/) :”The variation between a low and a high level challenge is likely to mobilize biological resources and activate defence mechanisms that can ultimately increase biological redundancy and improved damage repair rates. This implies that there must be a continuous variation of challenging stimuli, without ever reaching a stage of exhaustion” (in this case, mental exhaustion).