Ending aging
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Aubrey de Grey's science of ending aging

Summary
In his talk 'The Science of Ending Aging' Aubrey de Grey argues we should invest more in maintenance of our bodies.  In this page we summarize his video comments and then use complex adaptive system (
This page introduces the complex adaptive system (CAS) theory frame.  The theory is positioned relative to the natural sciences.  It catalogs the laws and strategies which underpin the operation of systems that are based on the interaction of emergent agents. 
John Holland's framework for representing complexity is outlined.  Links to other key aspects of CAS theory discussed at the site are presented. 
CAS
) theory to review his arguments.  Focusing the lens of CAS theory and mechanisms of emergence on the system we highlight the pros and cons of ending aging. 
Introduction
The biomedical gerontologist Aubrey de Grey argues in his YouTube video The Science of Ending Aging that we must shift our view of aging to include degenerative processes such as heart disease is cardiovascular disease which refers to:
  • Conditions where narrowed and blocked blood vessels result in angina, hypertension, CHD and heart attacks and hemorrhagic/ischemic strokes.  Mutations of the gene PCSK9 have been implicated in cardiovascular disease.  Rare families with dominant inheritence of the mutations have an overactive protein, very high levels of blood cholesterol and cardiac disease. Other rare PCSK9 mutations result in an 88% reduced risk from heart disease.  
, Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It is initiated by an increasingly leaky blood-brain barrier and the innate immune response to subsequent infections (May 2016).  The Alzheimer's pathway follows:
  • Plaques form and set off the formation of tangled thread-like tau protein.
    • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
    • BACE inhibitors block an enzyme needed to form amyloid. 
  • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
  • The brain becomes inflamed resulting in the killing of many more nerve cells. 
.  Further he argues we should proactively limit the damage caused to our bodies by living. 

De Grey initially highlights the cost of coping with aging in the US is the United States of America.  .  The success of constraining infectious diseases has allowed more and more people to live beyond 65.  But that means more and more money will be needed to cope with chronic diseases if current trends continue.  But only 3% of the NIH is the National Institute of Health, Bethesda Maryland.  It is the primary federal agency for the support and conduct of biomedical and behavioral research.  It is also one of the four US special containment units of the CDC.   budget is spent on aging!  What is aging?  De Grey uses "The life-long accumulation of damage to the tissues, cells and molecules of the body that occurs as an intrinsic side-effect of the body's normal operation."  Diseases of aging such as cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).  , Alzheimer's disease and heart disease are currently viewed as being like all other diseases and are researched, diagnosed and treated similarly.  However, de Grey suggests a change of approach -- to treat them as the result of poor maintenance which implies they can't be eliminated -- unlike most acute diseases where removal of the cause is the key treatment strategy. 

He asserts a three stage process currently operates:
  1. Metabolism's operation causes
  2. Damage of various types to the infrastructure of the body.  Over time this leads to
  3. Pathology (impacted function)
The transition from stage 1 to stage 2 is currently studied by gerontologists who aim to clean up metabolism by slowing down the processes that cause damage.  De Grey views tweaking the problematic metabolic processes while leaving the rest operating effectively as a hopeless strategy since it requires having a clear understanding of all the molecular processes, good and bad, that evolution has deployed in the body which de Grey suggests is both implausible and consumes a lot of money. 

The transition from stage 2 to stage 3 is studied by geriatrics researchers who de Grey asserts ignore the maintenance issues.  Their strategy is to target pathologies assuming that they can be eliminated from the body.  De Grey sees the approach being undermined by these invalid assumptions and the vast set of pathologies that develops as we get older. 

He argues research into the process of damaging the infrastructure is not receiving enough investment.  He suggests research can identify specific maintenance strategies (Replace, Remove, Repair or Reinforce) that can inhibit the pathologies that we see as aging.  De Grey uses the analogy of car maintenance which limits the cumulative wear and tear on the car. 

Gerontologists have developed a model that describes the types of damage that metabolism causes to our bodies:
  1. Cell loss,
  2. Division-obsessed cells,
  3. Death-resistant cells,
  4. Mitochondrial mutations,
  5. Intracellular junk,
  6. Extracellular junk,
  7. Extracellular matrix stiffening. 

The mappings between the pathologies and the types of damage is widely understood and accepted. 

Aubrey asserts that cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).   is typically associated with 2.  He concedes that cancer's integration with evolved genomic operations makes it a hard problem for maintenance to solve.  But most other chronic pathologies are associated with multiple of the other types he suggests:

De Grey argues that the power of the maintenance approach is due to the generic nature of the damage mechanisms.   Undermining the seven mechanisms should improve many different metabolic operations in the body. 

He describes a separate method to address each category:


De Grey is working on atherosclerosis which he argues is mainly due to the buildup over time of specific toxic residues that the body fails to break down.  In particular he highlights the buildup of 7-Ketocholesterol which he argues is toxic to macrophages are differentiated monocytes.  They are found in all tissue types.  They have specialized to perform phagocytosis ingesting pathogens into phagosomes which  then fuse with a lysosome whence the pathogen is digested.  They can digest more than 100 bacteria before they die due to the build up of their own metabolytes.  They play a critical role in innate immunity and help initiate adaptive immunity by recruiting other immune cells such as lymphocytes by presenting antigens from the digested pathogen.  M1 macrophages encourage inflammation.  M2 macrophages decrease inflamation and support tissue repair.  .  As they ingest the toxin they transform into foam cells which also contribute to the damage.  De Grey explains an approach that his institute, the SENS research foundation, is pursuing to limit the buildup of 7-Ketocholesterol.  Certain soil bacteria are able to metabolize and break it down.  By leveraging the bacterial gene de Grey hopes to provide our eukaryotic cells, a relatively large multi-component cell type from which yeast and multi-celled plants and animals, including humans, is constructed.  It contains modules including a nucleus and production functions such as mitochondria.   lysosomes is a membrane-bound cell organelle containing hydrolitic enzymes. 
with this infrastructure that will breakdown the toxin inhibiting the buildup. 

De Grey proposes to treat Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It is initiated by an increasingly leaky blood-brain barrier and the innate immune response to subsequent infections (May 2016).  The Alzheimer's pathway follows:
  • Plaques form and set off the formation of tangled thread-like tau protein.
    • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
    • BACE inhibitors block an enzyme needed to form amyloid. 
  • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
  • The brain becomes inflamed resulting in the killing of many more nerve cells. 
by encouraging phagocytosis is the engulfing of a solid particle, such as a bacteria, by a eucaryotic cell such as a macrophage into an internal vesicle termed a phagosome.  In the immune system cells (leukocytes) the phagosome is then combined with a lysosome enabling the breakdown of the solid particle. 
by the immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
of the amyloid deposits. 

De Grey states that his maintenance approach will eventually develop into the biggest industry of all time.  He must catch the attention of angel and venture investors so his claim may be tailored to this need. 
Similarly he views critics worried about the potential for over population inherent in his success as suffering from myopia about the need for the maintenance approach - fearful is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger. 
of the unknown and of getting their hopes dashed.  He argues more must be done to allow people to enjoy old age which will also reduce the current burden of treating their diseases. 

When using
This page introduces the complex adaptive system (CAS) theory frame.  The theory is positioned relative to the natural sciences.  It catalogs the laws and strategies which underpin the operation of systems that are based on the interaction of emergent agents. 
John Holland's framework for representing complexity is outlined.  Links to other key aspects of CAS theory discussed at the site are presented. 
complex adaptive system (CAS) theory
to analyze Aubrey de Grey's comments it appears:
We hope that our CAS based comments help support the continued scientific evaluations of both our personal and society's health. 


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