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Sunday, March 14, 2021

Immortality

From Wikipedia, the free encyclopedia

The Fountain of Eternal Life in Cleveland, Ohio is described as symbolizing "Man rising above death, reaching upward to God and toward Peace."

Immortality is eternal life, being exempt from death; unending existence. Some modern species may possess biological immortality.

Certain scientists, futurists, and philosophers have theorized about the immortality of the human body, with some suggesting that human immortality may be achievable in the first few decades of the 21st century. Other advocates believe that life extension is a more achievable goal in the short term, with immortality awaiting further research breakthroughs. The absence of ageing would provide humans with biological immortality, but not invulnerability to death by disease or physical trauma; although mind uploading could solve that if it proved possible. Whether the process of internal endoimmortality is delivered within the upcoming years depends chiefly on research (and in neuron research in the case of endoimmortality through an immortalized cell line) in the former view and perhaps is an awaited goal in the latter case.

In religious contexts, immortality is often stated to be one of the promises of God (or other deities) to human beings who show goodness or else follow divine law. What form an unending human life would take, or whether an immaterial soul exists and possesses immortality, has been a major point of focus of religion, as well as the subject of speculation and debate.

Definitions

Scientific

Life extension technologies promise a path to complete rejuvenation. Cryonics holds out the hope that the dead can be revived in the future, following sufficient medical advancements. While, as shown with creatures such as hydra and planarian worms, it is indeed possible for a creature to be biologically immortal, it is not known if it will be possible for humans in the near-future.

Mind uploading is the transference of brain states from a human brain to an alternative medium providing similar functionality. Assuming the process to be possible and repeatable, this would provide immortality to the computation of the original brain, as predicted by futurists such as Ray Kurzweil.

Religious

Immortality in religion refers usually to either the belief in physical immortality or a more spiritual afterlife.

The notion that immortality equals the eternal union of body and soul is typical of many religions. In traditions, such as ancient Egyptian religion, Mesopotamian religion, and Greek religion, the immortal gods consequently were considered to have physical bodies. In Mesopotamian and Greek religion, the gods also made certain men and women physical immortal, whereas in large parts of Christianity the belief that all true believers will be resurrected to physical immortality is a pivotal tenet. Similar beliefs that physical immortality is possible are held by Rastafarians or Rebirthers.

Alchemy

Alchemists strive to solve the mystery of immortality with the Philosopher's Stone and elixir of life. They believe through the application of alchemical processes, the physical body can be maintained through infinity, not dying by any natural diseases, only finding an end through physical destruction of the body. Theoretically if one could stay out of harm's way one could live forever.

Physical immortality

Physical immortality is a state of life that allows a person to avoid death and maintain conscious thought. It can mean the unending existence of a person from a physical source other than organic life, such as a computer. Active pursuit of physical immortality can either be based on scientific trends, such as cryonics, digital immortality, breakthroughs in rejuvenation, or predictions of an impending technological singularity.

Causes of death

There are three main causes of death: aging, disease and physical trauma. Such issues can be resolved with the solutions provided in research to any end providing such alternate theories at present that require unification.

Aging

Aubrey de Grey, a leading researcher in the field, defines aging as "a collection of cumulative changes to the molecular and cellular structure of an adult organism, which result in essential metabolic processes, but which also, once they progress far enough, increasingly disrupt metabolism, resulting in pathology and death." The current causes of aging in humans are cell loss (without replacement), DNA damage, oncogenic nuclear mutations and epimutations, cell senescence, mitochondrial mutations, lysosomal aggregates, extracellular aggregates, random extracellular cross-linking, immune system decline, and endocrine changes. Eliminating aging would require finding a solution to each of these causes, a program de Grey calls engineered negligible senescence. There is also a huge body of knowledge indicating that change is characterized by the loss of molecular fidelity.

Disease

Disease is theoretically surmountable via technology. In short, it is an abnormal condition affecting the body of an organism, something the body shouldn't typically have to deal with its natural make up. Human understanding of genetics is leading to cures and treatments for a myriad of previously incurable diseases. The mechanisms by which other diseases do damage are becoming better understood. Sophisticated methods of detecting diseases early are being developed. Preventative medicine is becoming better understood. Neurodegenerative diseases like Parkinson's and Alzheimer's may soon be curable with the use of stem cells. Breakthroughs in cell biology and telomere research are leading to treatments for cancer. Vaccines are being researched for AIDS and tuberculosis. Genes associated with type 1 diabetes and certain types of cancer have been discovered, allowing for new therapies to be developed. Artificial devices attached directly to the nervous system may restore sight to the blind. Drugs are being developed to treat a myriad of other diseases and ailments.

Trauma

Physical trauma would remain as a threat to perpetual physical life, as an otherwise immortal person would still be subject to unforeseen accidents or catastrophes. The speed and quality of paramedic response remains a determining factor in surviving severe trauma. A body that could automatically repair itself from severe trauma, such as speculated uses for nanotechnology, would mitigate this factor. Being the seat of consciousness, the brain cannot be risked to trauma if a continuous physical life is to be maintained. This aversion to trauma risk to the brain would naturally result in significant behavioral changes that would render physical immortality undesirable for some people.

Environmental change

Organisms otherwise unaffected by these causes of death would still face the problem of obtaining sustenance (whether from currently available agricultural processes or from hypothetical future technological processes) in the face of changing availability of suitable resources as environmental conditions change. After avoiding aging, disease, and trauma, death through resource limitation is still possible, such as hypoxia or starvation.

If there is no limitation on the degree of gradual mitigation of risk then it is possible that the cumulative probability of death over an infinite horizon is less than certainty, even when the risk of fatal trauma in any finite period is greater than zero. Mathematically, this is an aspect of achieving "actuarial escape velocity"

Biological immortality

Human chromosomes (grey) capped by telomeres (white)

Biological immortality is an absence of aging. Specifically it is the absence of a sustained increase in rate of mortality as a function of chronological age. A cell or organism that does not experience aging, or ceases to age at some point, is biologically immortal.

Biologists have chosen the word "immortal" to designate cells that are not limited by the Hayflick limit, where cells no longer divide because of DNA damage or shortened telomeres. The first and still most widely used immortal cell line is HeLa, developed from cells taken from the malignant cervical tumor of Henrietta Lacks without her consent in 1951. Prior to the 1961 work of Leonard Hayflick, there was the erroneous belief fostered by Alexis Carrel that all normal somatic cells are immortal. By preventing cells from reaching senescence one can achieve biological immortality; telomeres, a "cap" at the end of DNA, are thought to be the cause of cell aging. Every time a cell divides the telomere becomes a bit shorter; when it is finally worn down, the cell is unable to split and dies. Telomerase is an enzyme which rebuilds the telomeres in stem cells and cancer cells, allowing them to replicate an infinite number of times. No definitive work has yet demonstrated that telomerase can be used in human somatic cells to prevent healthy tissues from aging. On the other hand, scientists hope to be able to grow organs with the help of stem cells, allowing organ transplants without the risk of rejection, another step in extending human life expectancy. These technologies are the subject of ongoing research, and are not yet realized.

Biologically immortal species

Life defined as biologically immortal is still susceptible to causes of death besides aging, including disease and trauma, as defined above. Notable immortal species include:

  • Bacteria – Bacteria reproduce through binary fission. A parent bacterium splits itself into two identical daughter cells which eventually then split themselves in half. This process repeats, thus making the bacterium essentially immortal. A 2005 PLoS Biology paper suggests that after each division the daughter cells can be identified as the older and the younger, and the older is slightly smaller, weaker, and more likely to die than the younger.
  • Turritopsis dohrnii, a jellyfish (phylum Cnidaria, class Hydrozoa, order Anthoathecata), after becoming a sexually mature adult, can transform itself back into a polyp using the cell conversion process of transdifferentiation. Turritopsis dohrnii repeats this cycle, meaning that it may have an indefinite lifespan. Its immortal adaptation has allowed it to spread from its original habitat in the Caribbean to "all over the world".
  • Hydra is a genus belonging to the phylum Cnidaria, the class Hydrozoa and the order Anthomedusae. They are simple fresh-water predatory animals possessing radial symmetry.
  • Bristlecone pines are speculated to be potentially immortal; the oldest known living specimen is over 5,000 years old.

Evolution of aging

As the existence of biologically immortal species demonstrates, there is no thermodynamic necessity for senescence: a defining feature of life is that it takes in free energy from the environment and unloads its entropy as waste. Living systems can even build themselves up from seed, and routinely repair themselves. Aging is therefore presumed to be a byproduct of evolution, but why mortality should be selected for remains a subject of research and debate. Programmed cell death and the telomere "end replication problem" are found even in the earliest and simplest of organisms. This may be a tradeoff between selecting for cancer and selecting for aging.

Modern theories on the evolution of aging include the following:

  • Mutation accumulation is a theory formulated by Peter Medawar in 1952 to explain how evolution would select for aging. Essentially, aging is never selected against, as organisms have offspring before the mortal mutations surface in an individual.
  • Antagonistic pleiotropy is a theory proposed as an alternative by George C. Williams, a critic of Medawar, in 1957. In antagonistic pleiotropy, genes carry effects that are both beneficial and detrimental. In essence this refers to genes that offer benefits early in life, but exact a cost later on, i.e. decline and death.
  • The disposable soma theory was proposed in 1977 by Thomas Kirkwood, which states that an individual body must allocate energy for metabolism, reproduction, and maintenance, and must compromise when there is food scarcity. Compromise in allocating energy to the repair function is what causes the body gradually to deteriorate with age, according to Kirkwood.

Prospects for human biological immortality

Life-extending substances

Some scientists believe that boosting the amount or proportion of telomerase in the body, a naturally forming enzyme that helps maintain the protective caps at the ends of chromosomes, could prevent cells from dying and so may ultimately lead to extended, healthier lifespans. A team of researchers at the Spanish National Cancer Centre (Madrid) tested the hypothesis on mice. It was found that those mice which were "genetically engineered to produce 10 times the normal levels of telomerase lived 50% longer than normal mice".

In normal circumstances, without the presence of telomerase, if a cell divides repeatedly, at some point all the progeny will reach their Hayflick limit. With the presence of telomerase, each dividing cell can replace the lost bit of DNA, and any single cell can then divide unbounded. While this unbounded growth property has excited many researchers, caution is warranted in exploiting this property, as exactly this same unbounded growth is a crucial step in enabling cancerous growth. If an organism can replicate its body cells faster, then it would theoretically stop aging.

Embryonic stem cells express telomerase, which allows them to divide repeatedly and form the individual. In adults, telomerase is highly expressed in cells that need to divide regularly (e.g., in the immune system), whereas most somatic cells express it only at very low levels in a cell-cycle dependent manner.

Technological immortality, biological machines, and "swallowing the doctor"

Technological immortality is the prospect for much longer life spans made possible by scientific advances in a variety of fields: nanotechnology, emergency room procedures, genetics, biological engineering, regenerative medicine, microbiology, and others. Contemporary life spans in the advanced industrial societies are already markedly longer than those of the past because of better nutrition, availability of health care, standard of living and bio-medical scientific advances. Technological immortality predicts further progress for the same reasons over the near term. An important aspect of current scientific thinking about immortality is that some combination of human cloning, cryonics or nanotechnology will play an essential role in extreme life extension. Robert Freitas, a nanorobotics theorist, suggests tiny medical nanorobots could be created to go through human bloodstreams, find dangerous things like cancer cells and bacteria, and destroy them. Freitas anticipates that gene-therapies and nanotechnology will eventually make the human body effectively self-sustainable and capable of living indefinitely in empty space, short of severe brain trauma. This supports the theory that we will be able to continually create biological or synthetic replacement parts to replace damaged or dying ones. Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair devices, including ones operating within cells and utilizing as yet hypothetical biological machines, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030. According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical micromachines. Hibbs suggested that certain repair machines might one day be reduced in size to the point that it would, in theory, be possible to (as Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.

Cryonics

Cryonics, the practice of preserving organisms (either intact specimens or only their brains) for possible future revival by storing them at cryogenic temperatures where metabolism and decay are almost completely stopped, can be used to 'pause' for those who believe that life extension technologies will not develop sufficiently within their lifetime. Ideally, cryonics would allow clinically dead people to be brought back in the future after cures to the patients' diseases have been discovered and aging is reversible. Modern cryonics procedures use a process called vitrification which creates a glass-like state rather than freezing as the body is brought to low temperatures. This process reduces the risk of ice crystals damaging the cell-structure, which would be especially detrimental to cell structures in the brain, as their minute adjustment evokes the individual's mind.

Mind-to-computer uploading

One idea that has been advanced involves uploading an individual's habits and memories via direct mind-computer interface. The individual's memory may be loaded to a computer or to a new organic body. Extropian futurists like Moravec and Kurzweil have proposed that, thanks to exponentially growing computing power, it will someday be possible to upload human consciousness onto a computer system, and exist indefinitely in a virtual environment. This could be accomplished via advanced cybernetics, where computer hardware would initially be installed in the brain to help sort memory or accelerate thought processes. Components would be added gradually until the person's entire brain functions were handled by artificial devices, avoiding sharp transitions that would lead to issues of identity, thus running the risk of the person to be declared dead and thus not be a legitimate owner of his or her property. After this point, the human body could be treated as an optional accessory and the program implementing the person could be transferred to any sufficiently powerful computer. Another possible mechanism for mind upload is to perform a detailed scan of an individual's original, organic brain and simulate the entire structure in a computer. What level of detail such scans and simulations would need to achieve to emulate awareness, and whether the scanning process would destroy the brain, is still to be determined. It is suggested that achieving immortality through this mechanism would require specific consideration to be given to the role of consciousness in the functions of the mind. An uploaded mind would only be a copy of the original mind, and not the conscious mind of the living entity associated in such a transfer. Without a simultaneous upload of consciousness, the original living entity remains mortal, thus not achieving true immortality. Research on neural correlates of consciousness is yet inconclusive on this issue. Whatever the route to mind upload, persons in this state could then be considered essentially immortal, short of loss or traumatic destruction of the machines that maintained them.

A modern day example of Mind-to-computer immortality is displayed in Netflix's show Altered Carbon. In this show, immortality has been achieved through the use of "stacks" (modules that contain the consciousness of a person and is transferable). Altered Carbon displays both the ethics and qualities of enabling such a use of immortality. However, a main point to focus on here is that the timeline in the show is hundreds of years into the future. This is important to note because in today's time, millions of dollars are being poured into this venture with very little success. As discussed above, a common theme correlated with "mind uploading" is cybernetics, in which this case, a "stack" could be considered cybernetic.

Cybernetics

Transforming a human into a cyborg can include brain implants or extracting a human processing unit and placing it in a robotic life-support system. Even replacing biological organs with robotic ones could increase life span (e.g. pace makers) and depending on the definition, many technological upgrades to the body, like genetic modifications or the addition of nanobots would qualify an individual as a cyborg. Some people believe that such modifications would make one impervious to aging and disease and theoretically immortal unless killed or destroyed.

Religious views

As late as 1952, the editorial staff of the Syntopicon found in their compilation of the Great Books of the Western World, that "The philosophical issue concerning immortality cannot be separated from issues concerning the existence and nature of man's soul." Thus, the vast majority of speculation on immortality before the 21st century was regarding the nature of the afterlife.

Ancient Greek religion

Immortality in ancient Greek religion originally always included an eternal union of body and soul as can be seen in Homer, Hesiod, and various other ancient texts. The soul was considered to have an eternal existence in Hades, but without the body the soul was considered dead. Although almost everybody had nothing to look forward to but an eternal existence as a disembodied dead soul, a number of men and women were considered to have gained physical immortality and been brought to live forever in either Elysium, the Islands of the Blessed, heaven, the ocean or literally right under the ground. Among these were Amphiaraus, Ganymede, Ino, Iphigenia, Menelaus, Peleus, and a great part of those who fought in the Trojan and Theban wars. Some were considered to have died and been resurrected before they achieved physical immortality. Asclepius was killed by Zeus only to be resurrected and transformed into a major deity. In some versions of the Trojan War myth, Achilles, after being killed, was snatched from his funeral pyre by his divine mother Thetis, resurrected, and brought to an immortal existence in either Leuce, the Elysian plains, or the Islands of the Blessed. Memnon, who was killed by Achilles, seems to have received a similar fate. Alcmene, Castor, Heracles, and Melicertes were also among the figures sometimes considered to have been resurrected to physical immortality. According to Herodotus' Histories, the 7th century BC sage Aristeas of Proconnesus was first found dead, after which his body disappeared from a locked room. Later he was found not only to have been resurrected but to have gained immortality.

The parallel between these traditional beliefs and the later resurrection of Jesus was not lost on early Christians, as Justin Martyr argued: "when we say ... Jesus Christ, our teacher, was crucified and died, and rose again, and ascended into heaven, we propose nothing different from what you believe regarding those whom you consider sons of Zeus."

The philosophical idea of an immortal soul was a belief first appearing with either Pherecydes or the Orphics, and most importantly advocated by Plato and his followers. This, however, never became the general norm in Hellenistic thought. As may be witnessed even into the Christian era, not least by the complaints of various philosophers over popular beliefs, many or perhaps most traditional Greeks maintained the conviction that certain individuals were resurrected from the dead and made physically immortal and that others could only look forward to an existence as disembodied and dead, though everlasting, souls.

Buddhism

According to one Tibetan Buddhist teaching, Dzogchen, individuals can transform the physical body into an immortal body of light called the rainbow body.

Christianity

Adam and Eve condemned to mortality. Hans Holbein the Younger, Danse Macabre, 16th century

Christian theology holds that Adam and Eve lost physical immortality for themselves and all their descendants in the Fall of man, although this initial "imperishability of the bodily frame of man" was "a preternatural condition".

Christians who profess the Nicene Creed believe that every dead person (whether they believed in Christ or not) will be resurrected from the dead at the Second Coming, and this belief is known as Universal resurrection. While Paul the Apostle insisted that the resurrected body was only "spiritual" and that "flesh and blood cannot inherit the kingdom of God", the Gospels increasingly emphasized the physical nature of the resurrection body – as the resurrected Jesus in the Gospel of Luke insisting on his still consisting of "flesh and bones". This shift may have been in response to traditional Greek expectations that immortality always included both body and soul.

N.T. Wright, a theologian and former Bishop of Durham, has said many people forget the physical aspect of what Jesus promised. He told Time: "Jesus' resurrection marks the beginning of a restoration that he will complete upon his return. Part of this will be the resurrection of all the dead, who will 'awake', be embodied and participate in the renewal. Wright says John Polkinghorne, a physicist and a priest, has put it this way: 'God will download our software onto his hardware until the time he gives us new hardware to run the software again for ourselves.' That gets to two things nicely: that the period after death (the Intermediate state) is a period when we are in God's presence but not active in our own bodies, and also that the more important transformation will be when we are again embodied and administering Christ's kingdom." This kingdom will consist of Heaven and Earth "joined together in a new creation", he said.

Hinduism

Representation of a soul undergoing punarjanma. Illustration from Hinduism Today, 2004

Hindus believe in an immortal soul which is reincarnated after death. According to Hinduism, people repeat a process of life, death, and rebirth in a cycle called samsara. If they live their life well, their karma improves and their station in the next life will be higher, and conversely lower if they live their life poorly. After many life times of perfecting its karma, the soul is freed from the cycle and lives in perpetual bliss. There is no place of eternal torment in Hinduism, although if a soul consistently lives very evil lives, it could work its way down to the very bottom of the cycle.

There are explicit renderings in the Upanishads alluding to a physically immortal state brought about by purification, and sublimation of the 5 elements that make up the body. For example, in the Shvetashvatara Upanishad (Chapter 2, Verse 12), it is stated "When earth, water, fire, air and sky arise, that is to say, when the five attributes of the elements, mentioned in the books on yoga, become manifest then the yogi's body becomes purified by the fire of yoga and he is free from illness, old age and death."

Another view of immortality is traced to the Vedic tradition by the interpretation of Maharishi Mahesh Yogi:

That man indeed whom these (contacts)
do not disturb, who is even-minded in
pleasure and pain, steadfast, he is fit
for immortality, O best of men.

To Maharishi Mahesh Yogi, the verse means, "Once a man has become established in the understanding of the permanent reality of life, his mind rises above the influence of pleasure and pain. Such an unshakable man passes beyond the influence of death and in the permanent phase of life: he attains eternal life ... A man established in the understanding of the unlimited abundance of absolute existence is naturally free from existence of the relative order. This is what gives him the status of immortal life."

An Indian Tamil saint known as Vallalar claimed to have achieved immortality before disappearing forever from a locked room in 1874.

Judaism

The traditional concept of an immaterial and immortal soul distinct from the body was not found in Judaism before the Babylonian exile, but developed as a result of interaction with Persian and Hellenistic philosophies. Accordingly, the Hebrew word nephesh, although translated as "soul" in some older English Bibles, actually has a meaning closer to "living being". Nephesh was rendered in the Septuagint as ψυχή (psūchê), the Greek word for soul.

The only Hebrew word traditionally translated "soul" (nephesh) in English language Bibles refers to a living, breathing conscious body, rather than to an immortal soul. In the New Testament, the Greek word traditionally translated "soul" (ψυχή) has substantially the same meaning as the Hebrew, without reference to an immortal soul. 'Soul' may refer to the whole person, the self: 'three thousand souls' were converted in Acts 2:41 (see Acts 3:23).

The Hebrew Bible speaks about Sheol (שאול), originally a synonym of the grave-the repository of the dead or the cessation of existence until the resurrection of the dead. This doctrine of resurrection is mentioned explicitly only in Daniel 12:1–4 although it may be implied in several other texts. New theories arose concerning Sheol during the intertestamental period.

The views about immortality in Judaism is perhaps best exemplified by the various references to this in Second Temple period. The concept of resurrection of the physical body is found in 2 Maccabees, according to which it will happen through recreation of the flesh. Resurrection of the dead also appears in detail in the extra-canonical books of Enoch, and in Apocalypse of Baruch. According to the British scholar in ancient Judaism Philip R. Davies, there is "little or no clear reference ... either to immortality or to resurrection from the dead" in the Dead Sea scrolls texts. Both Josephus and the New Testament record that the Sadducees did not believe in an afterlife, but the sources vary on the beliefs of the Pharisees. The New Testament claims that the Pharisees believed in the resurrection, but does not specify whether this included the flesh or not. According to Josephus, who himself was a Pharisee, the Pharisees held that only the soul was immortal and the souls of good people will be reincarnated and "pass into other bodies," while "the souls of the wicked will suffer eternal punishment."  Jubilees seems to refer to the resurrection of the soul only, or to a more general idea of an immortal soul.

Rabbinic Judaism claims that the righteous dead will be resurrected in the Messianic Age with the coming of the messiah. They will then be granted immortality in a perfect world. The wicked dead, on the other hand, will not be resurrected at all. This is not the only Jewish belief about the afterlife. The Tanakh is not specific about the afterlife, so there are wide differences in views and explanations among believers.

Taoism

It is repeatedly stated in the Lüshi Chunqiu that death is unavoidable. Henri Maspero noted that many scholarly works frame Taoism as a school of thought focused on the quest for immortality. Isabelle Robinet asserts that Taoism is better understood as a way of life than as a religion, and that its adherents do not approach or view Taoism the way non-Taoist historians have done. In the Tractate of Actions and their Retributions, a traditional teaching, spiritual immortality can be rewarded to people who do a certain amount of good deeds and live a simple, pure life. A list of good deeds and sins are tallied to determine whether or not a mortal is worthy. Spiritual immortality in this definition allows the soul to leave the earthly realms of afterlife and go to pure realms in the Taoist cosmology.

Zoroastrianism

Zoroastrians believe that on the fourth day after death, the human soul leaves the body and the body remains as an empty shell. Souls would go to either heaven or hell; these concepts of the afterlife in Zoroastrianism may have influenced Abrahamic religions. The Persian word for "immortal" is associated with the month "Amurdad", meaning "deathless" in Persian, in the Iranian calendar (near the end of July). The month of Amurdad or Ameretat is celebrated in Persian culture as ancient Persians believed the "Angel of Immortality" won over the "Angel of Death" in this month.

Philosophical arguments for the immortality of the soul

Alcmaeon of Croton

Alcmaeon of Croton argued that the soul is continuously and ceaselessly in motion. The exact form of his argument is unclear, but it appears to have influenced Plato, Aristotle, and other later writers.

Plato

Plato's Phaedo advances four arguments for the soul's immortality:

  • The Cyclical Argument, or Opposites Argument explains that Forms are eternal and unchanging, and as the soul always brings life, then it must not die, and is necessarily "imperishable". As the body is mortal and is subject to physical death, the soul must be its indestructible opposite. Plato then suggests the analogy of fire and cold. If the form of cold is imperishable, and fire, its opposite, was within close proximity, it would have to withdraw intact as does the soul during death. This could be likened to the idea of the opposite charges of magnets.
  • The Theory of Recollection explains that we possess some non-empirical knowledge (e.g. The Form of Equality) at birth, implying the soul existed before birth to carry that knowledge. Another account of the theory is found in Plato's Meno, although in that case Socrates implies anamnesis (previous knowledge of everything) whereas he is not so bold in Phaedo.
  • The Affinity Argument, explains that invisible, immortal, and incorporeal things are different from visible, mortal, and corporeal things. Our soul is of the former, while our body is of the latter, so when our bodies die and decay, our soul will continue to live.
  • The Argument from Form of Life or The Final Argument explains that the Forms, incorporeal and static entities, are the cause of all things in the world, and all things participate in Forms. For example, beautiful things participate in the Form of Beauty; the number four participates in the Form of the Even, etc. The soul, by its very nature, participates in the Form of Life, which means the soul can never die.

Plotinus

Plotinus offers a version of the argument that Kant calls "The Achilles of Rationalist Psychology". Plotinus first argues that the soul is simple, then notes that a simple being cannot decompose. Many subsequent philosophers have argued both that the soul is simple and that it must be immortal. The tradition arguably culminates with Moses Mendelssohn's Phaedon.

Metochites

Theodore Metochites argues that part of the soul's nature is to move itself, but that a given movement will cease only if what causes the movement is separated from the thing moved – an impossibility if they are one and the same.

Avicenna

Avicenna argued for the distinctness of the soul and the body, and the incorruptibility of the former.

Aquinas

The full argument for the immortality of the soul and Thomas Aquinas' elaboration of Aristotelian theory is found in Question 75 of the First Part of the Summa Theologica.

Descartes

René Descartes endorses the claim that the soul is simple, and also that this entails that it cannot decompose. Descartes does not address the possibility that the soul might suddenly disappear.

Leibniz

In early work, Gottfried Wilhelm Leibniz endorses a version of the argument from the simplicity of the soul to its immortality, but like his predecessors, he does not address the possibility that the soul might suddenly disappear. In his monadology he advances a sophisticated novel argument for the immortality of monads.

Moses Mendelssohn

Moses Mendelssohn's Phaedon is a defense of the simplicity and immortality of the soul. It is a series of three dialogues, revisiting the Platonic dialogue Phaedo, in which Socrates argues for the immortality of the soul, in preparation for his own death. Many philosophers, including Plotinus, Descartes, and Leibniz, argue that the soul is simple, and that because simples cannot decompose they must be immortal. In the Phaedon, Mendelssohn addresses gaps in earlier versions of this argument (an argument that Kant calls the Achilles of Rationalist Psychology). The Phaedon contains an original argument for the simplicity of the soul, and also an original argument that simples cannot suddenly disappear. It contains further original arguments that the soul must retain its rational capacities as long as it exists.

Ethics

The possibility of clinical immortality raises a host of medical, philosophical, and religious issues and ethical questions. These include persistent vegetative states, the nature of personality over time, technology to mimic or copy the mind or its processes, social and economic disparities created by longevity, and survival of the heat death of the universe.

Undesirability

Physical immortality has also been imagined as a form of eternal torment, as in Mary Shelley's short story "The Mortal Immortal", the protagonist of which witnesses everyone he cares about dying around him. Jorge Luis Borges explored the idea that life gets its meaning from death in the short story "The Immortal"; an entire society having achieved immortality, they found time becoming infinite, and so found no motivation for any action.

In his book Thursday's Fictions, and the stage and film adaptations of it, Richard James Allen tells the story of a woman named Thursday who tries to cheat the cycle of reincarnation to get a form of eternal life. At the end of this fantastical tale, her son, Wednesday, who has witnessed the havoc his mother's quest has caused, forgoes the opportunity for immortality when it is offered to him. Likewise, the novel Tuck Everlasting depicts immortality as "falling off the wheel of life" and is viewed as a curse as opposed to a blessing.

In Anne Rice's book series The Vampire Chronicles, vampires are portrayed as immortal and ageless, but their inability to cope with the changes in the world around them means that few vampires live for much more than a century, and those who do often view their changeless form as a curse.

Zardoz, a 1974 movie by John Boorman, features Eternals and Brutals, with the former having listless lives.

In The X-Files episode "Tithonus" (named after a Greek mythical character whose immortality was also highly unpleasant) Agent Scully meets an unhappy immortal man who is over two centuries old, after he had accidentally cheated death. He is miserable and longs for death. She queries him about why, arguing immortality is a great blessing. However, he replies that 70 years is all anyone really needs-after that it simply becomes unbearable. Elaborating, he tells her that after a time the details of his early life faded from his memory. As a result, he can no longer even remember his deceased wife's name. Further, being immortal has left him totally alone, since no one else has the same condition. He can also be wounded, though his injuries fade, and thus suffers yet still lives on.

In his book Death, Yale philosopher Shelly Kagan argues that any form of human immortality would be undesirable. Kagan's argument takes the form of a dilemma. Either our characters remain essentially the same in an immortal afterlife, or they do not. If our characters remain basically the same—that is, if we retain more or less the desires, interests, and goals that we have now—then eventually, over an infinite stretch of time, we will get bored and find eternal life unbearably tedious. If, on the other hand, our characters are radically changed—e.g., by God periodically erasing our memories or giving us rat-like brains that never tire of certain simple pleasures—then such a person would be too different from our current self for us to care much what happens to them. Either way, Kagan argues, immortality is unattractive. The best outcome, Kagan argues, would be for humans to live as long as they desired and then to accept death gratefully as rescuing us from the unbearable tedium of immortality.

Sociology

If human beings were to achieve immortality, there would most likely be a change in the world's social structures. Sociologists argue that human beings' awareness of their own mortality shapes their behavior. With the advancements in medical technology in extending human life, there may need to be serious considerations made about future social structures. The world is already experiencing a global demographic shift of increasingly ageing populations with lower replacement rates. The social changes that are made to accommodate this new population shift may be able to offer insight on the possibility of an immortal society.

Immortality would increase population growth, bringing with it many consequences as for example the impact of population growth on the environment and planetary boundaries.

Politics

Although some scientists state that radical life extension, delaying and stopping aging are achievable, there are no international or national programs focused on stopping aging or on radical life extension. In 2012 in Russia, and then in the United States, Israel and the Netherlands, pro-immortality political parties were launched. They aimed to provide political support to anti-aging and radical life extension research and technologies and at the same time transition to the next step, radical life extension, life without aging, and finally, immortality and aim to make possible access to such technologies to most currently living people.

Symbols

The ankh

There are numerous symbols representing immortality. The ankh is an Egyptian symbol of life that holds connotations of immortality when depicted in the hands of the gods and pharaohs, who were seen as having control over the journey of life. The Möbius strip in the shape of a trefoil knot is another symbol of immortality. Most symbolic representations of infinity or the life cycle are often used to represent immortality depending on the context they are placed in. Other examples include the Ouroboros, the Chinese fungus of longevity, the ten kanji, the phoenix, the peacock in Christianity, and the colors amaranth (in Western culture) and peach (in Chinese culture).

Fiction

Immortality is a popular subject in fiction, as it explores humanity's deep-seated fears and comprehension of its own mortality. Immortal beings and species abound in fiction, especially fantasy fiction, and the meaning of "immortal" tends to vary. The Epic of Gilgamesh, one of the first literary works, is primarily a quest of a hero seeking to become immortal.

Some fictional beings are completely immortal (or very nearly so) in that they are immune to death by injury, disease and age. Sometimes such powerful immortals can only be killed by each other, as is the case with the Q from the Star Trek series. Even if something can't be killed, a common plot device involves putting an immortal being into a slumber or limbo, as is done with Morgoth in J. R. R. Tolkien's The Silmarillion and the Dreaming God of Pathways Into Darkness. Storytellers often make it a point to give weaknesses to even the most indestructible of beings. For instance, Superman is supposed to be invulnerable, yet his enemies were able to exploit his now-infamous weakness: Kryptonite.

Many fictitious species are said to be immortal if they cannot die of old age, even though they can be killed through other means, such as injury. Modern fantasy elves often exhibit this form of immortality. Other creatures, such as vampires and the immortals in the film Highlander, can only die from beheading. The classic and stereotypical vampire is typically slain by one of several very specific means, including a silver bullet (or piercing with other silver weapons), a stake through the heart (perhaps made of consecrated wood), or by exposing them to sunlight.

The 2018 science fiction TV series Ad Vitam explored the social impact of biological immortality.

The 10,000 Year Explosion

From Wikipedia, the free encyclopedia
 
The 10,000 Year Explosion: How Civilization Accelerated Human Evolution
The 10,000 Year Explosion (Cover).jpg
AuthorsGregory Cochran
Henry Harpending
LanguageEnglish
SubjectRecent human evolution
GenreNon-fiction
PublisherBasic Books
Publication date
2009
Media typePrint
Pages304
ISBN0-465-00221-8
599.93'8-dc22
LC ClassGN281.4.c632 2009

The 10,000 Year Explosion: How Civilization Accelerated Human Evolution is a 2009 book by anthropologists Gregory Cochran and Henry Harpending. Starting with their own take on the conventional wisdom that the evolutionary process stopped when modern humans appeared, the authors explain the genetic basis of their view that human evolution is accelerating, illustrating it with some examples.

Reviewers considered that while the book raised valuable questions, some assumptions also relied on discredited views. It has been criticized for history oversimplification, not allowing to make predictions about future human evolution and for racialism reification.

Opinions in book

Cochran and Harpending put forward the idea that the development of agriculture has caused an enormous increase in the rate of human evolution, including numerous evolutionary adaptations to the different challenges and lifestyles that resulted. Moreover, they argue that these adaptations have varied across different human populations, depending on factors such as when the various groups developed agriculture, and the extent to which they mixed genetically with other population groups.

Such changes, they argue, include not just well-known physical and biological adaptations such as skin colour, disease resistance, and lactose tolerance, but also personality and cognitive adaptations that are starting to emerge from genetic research. These may include tendencies towards (for example) reduced physical strength, enhanced long-term planning, or increased docility, all of which may have been counter-productive in hunter-gatherer societies, but become favoured adaptations in a world of agriculture and its resulting trade, governments and urbanization. These adaptations are even more important in the modern world, and have helped shape today's nation states. The authors speculate that the scientific and Industrial Revolutions came about in part due to genetic changes in Europe over the past millennium, the absence of which had limited the progress of science in Ancient Greece. The authors suggest we would expect to see fewer adaptive changes among the Amerindians and sub-Saharan Africans, who have farmed for the shortest times and were genetically isolated from older civilizations by geographical barriers. In groups that had remained foragers, such as the Australian Aborigines, there would presumably be no such adaptations at all. This may explain why Indigenous Australians and many Native Americans have characteristic health problems when exposed to modern Western diets. Similarly, Amerindians, Aboriginals, and Polynesians, for example, had experienced very little infectious disease. They had not evolved immunities as did many Old World dwellers, and were decimated upon contact with the wider world.

Summary

The book's main thesis is that human civilisation greatly accelerated increases in the rates of evolution. The authors begin their discussion by providing two quotes they feel portray the conventional wisdom on this topic. First, they quote Ernst Mayr as stating in 1963: "Something must have happened to weaken the selective pressure drastically. We cannot escape the conclusion that man's evolution towards manness suddenly came to a halt." Second, they quote Stephen J. Gould as stating in 2000: "There's been no biological change in humans in 40,000 or 50,000 years. Everything we call culture and civilization we've built with the same body and brain."

This had become the established viewpoint—when modern humans appeared, evolution was essentially over. The received wisdom is based on the doctrine that human minds are the same, everywhere: Bastian's Psychic Unity of Mankind. Unfortunately, the authors find, this is no more than wishful thinking. Were it true, human bodies would also be the same worldwide, which clearly they are not. Finns cannot be mistaken for Zulus, nor Zulus for Finns. Not only are there strong reasons to believe that significant human evolution is theoretically possible, or even likely; it is completely obvious that it has taken place, since people are different from one another.

The first four of the book's seven chapters serve as a preamble to the final three. First, Cochran and Harpending present evidence for recent, accelerated human evolution after the invention of agriculture. In itself, this argument represents a paradigm shift, albeit one that now has clear data to back it up. The International HapMap Project and other studies have shown that selection is ongoing and has accelerated over time. This has been a key discovery in human biology, and Cochran and Harpending, building on their own work and that of others such as John Hawks of the University of Wisconsin-Madison, tie the advent of agriculture—and the selection pressures resulting from the new diets, new modes of habitation, new animal neighbors, and new modes of living that agriculture made possible—to this accelerating evolution.

Neanderthals

Wolpoff writes that Cochran and Harpending continue to refute conventional wisdom in their discussion of the Neanderthals. For natural selection to have a chance, they argue, there need to be favourable mutations, or favourable combinations of existing alleles such as genes for blue eyes or pale skin. Cochran and Harpending concentrate on the Neolithic farming revolution as the beginning of major population expansions that provided enough mutations to accelerate genetic change. Infectious diseases were another consequence of the early urban populations and soon became a new source of selection pressures. The origins of many recently adapted genes have now been traced to this period, creating effects such as regional differences in skin colour and skeletal gracility. Adaptations may have sacrificed muscle strength for higher intelligence and less aggressive human behaviours. By 5000 years ago, the authors estimate that adaptive alleles were coming into existence at a rate about 100 times faster than during the Pleistocene. This is the ‘‘explosion’’ of the book’s title.

Research cited by Cochran and Harpending provides evidence of genetic mixing between modern humans and an ancient Homo lineage such as the Neanderthals. According to Cochran and Harpending, it supports the idea that modern humans could have benefited by acquiring adaptive alleles evolved by our Neanderthal relatives - in this case, microcephalin, an adaptive allele associated with brain development. Microcephalin (MCPH1) regulates brain size, and has evolved under strong positive selection in the human evolutionary lineage. One genetic variant of Microcephalin, which arose about 37,000 years ago, increased its frequency in modern humans too rapidly, they argue, to be compatible with neutral genetic drift. As anatomically modern humans emerged from Africa and spread across the globe, the "indigenous" Homo populations they encountered had already inhabited their respective regions for long periods of time and might have been better adapted to the local environments than the colonizers. It follows, it is argued, that modern humans, although probably superior in their own way, could have benefited from adaptive alleles gained by interbreeding with the populations they replaced, as was proposed to be the case for the brain-size-determining gene microcephalin. However, analysis of the genomes of neanderthals did not find the microcephalin gene variant in question to be present, and later studies have not found the gene variant to be associated with mental ability.

Agriculture

Farming, which, the authors note, produces 10 to 100 times more calories per acre than foraging, carried this trend further. Over the period from 10,000 BC to AD 1, the world population increased about a hundredfold - estimates range from 40 to 170 times. An accelerated rate of evolution is a direct result of the larger human population. More people will have more mutations, thereby increasing opportunity for evolutionary change under natural selection. The spread of rapidly expanding populations eventually outpaced the spread of favourable mutations under selection in those populations, so for the first time in human history favourable mutations could not fully disperse throughout the human species. In addition, of course, selection pressures changed once farming was adopted, favouring distinctive adaptations in different geographic areas.

Gene flow

About halfway through the book, Cochran and Harpending pause to consider two different ways of looking at the information found in gene variants. Researchers commonly see them merely as markers of human migration, ignoring their functions. The authors support such research, but argue for a more complete understanding of the geographic distributions of genes. Where the usual geographical analysis treats the distribution of genes as an effect of history, in the authors' view, the genes themselves are a major cause: Two variants in the same gene do not necessarily have the same effect, and their relative, selective benefits will control the spread of genes through populations in both space and time.

Expansions

From that platform the authors discuss ideas that range from the possible origins of the Arthurian legend in Britain to the Spanish colonization of the Americas. Others have attempted this, for example in Jared Diamond's Guns, Germs, and Steel. But, according to Kelleher, Cochran and Harpending go one better than Diamond. He goes on to state that where Diamond was content with environmental determinism, at times opposing the roles of human biology and population differences, Cochran and Harpending embrace them both. Their discussion of gene flow becomes the core of an argument for biology as central to history, and the backdrop for the book's two major hypotheses.

The first seeks to resolve a longstanding debate in historical linguistics by making a case for the Kurgan hypothesis on the origins of the Indo-European language group. The Kurgan theory holds that Indo-European speakers came from lands between the Black and Caspian seas before spreading their language by conquest. The authors suggest that dairy farming and a complementary adaptation - the ability to digest lactose in adulthood - lie behind their conquests. With a walking food source, the milk-drinking warriors defeated their plant-growing neighbours. Drinking milk, from cows, horses, or camels, is a behavior shared by many of history's greatest conquering peoples, whether Kurgans, Scythians, Arabs, or Mongols. Without continuing evolution, the ability to digest milk could never have arisen. In fact, it has done so several times, in different ways, in various places, and it has helped shape human history. Kelleher comments that the authors’ argument makes it difficult to imagine the language in which their book would have been written, were it not for the ability to digest milk.

Ashkenazi Jews

The second major argument, which takes up the final chapter, sets out to explain why Ashkenazi Jews have a mean IQ so much higher than that of the population in general, as well as a higher rate of some genetic disorders such as Tay-Sachs disease. This argument had been published previously in an earlier paper. This hypothesis proposes that from A.D. 800 until around 1700, Askhenazi Jews were restricted to professions that required high intelligence, and that this produced a selective pressure in favor of intelligence. When faced with a sudden threat, evolution may favor any change that offers protection, and Cochran and Harpending propose that selection for genes promoting high intelligence thus had the side effect of also selecting for these genetic disorders. The hypothesis has drawn a mixed reaction from scientists, with some arguing the hypothesis is highly implausible, and others regarding it as worth considering. According to cognitive psychologist Steven Pinker, this theory "meets the standards of a good scientific theory, though it is tentative and could turn out to be mistaken." According to the Southern Poverty Law Center, these claims were based on the work of discredited psychologist Kevin MacDonald.

Reception

The paleoanthropologist Milford H. Wolpoff praised the book's central thesis as being insightful and worthy of further research, while also criticizing the book for its reification of biological race, and its dubious or oversimplified view of history.

In New Scientist, Christopher Willis wrote that the "evidence the authors present an overwhelming case that natural selection has recently acted strongly on us". However, Willis criticizes the authors for not discussing what the "recent and continuing evolution means for our species as a whole". Willis concludes by saying that "the book offers a limited and biased interpretation of some very exciting research".

In Evolutionary Psychology, Gregory Gorelik and Todd K. Shackelford wrote, "Although many of their arguments need more fleshing out and some may not withstand the assault of further scientific analysis, the authors are stunningly creative when considering human history. If even a handful of their arguments survive the onslaught of rigorous scientific scrutiny, Cochran and Harpending will have offered a valuable and novel approach to addressing questions of recent human evolution."

In Evolution and Human Behavior, anthropologist Edward Hagen wrote that the book makes "many unsupported and often questionable assertions", but it is nevertheless valuable in raising "bold questions about major historical encounters between populations — Neanderthal and modern humans, German tribes and Romans, Europeans and Native Americans — in light of formidable (but not unassailable) arguments from population genetics". Hagen considered that it "should also be on the summer reading list of all evolutionary social scientists".

Anthropologist Cadell Last wrote that by using race as a natural fact, the book "undermines the attempt to find a legitimate scientific approach to understanding recent human evolution and conceptualizing human genetic diversity" and that it was "unfortunate" that it had received "praise from prominent, influential well-established biological anthropologists" such as John D. Hawks.

Evolutionary anthropologist Keith Hunley, writing for the Journal of Anthropological Research, described the book's thesis as interesting, but said the list of behavioral adaptations supposedly favored by agricultural lifeways was "bizarre". Per Hunley, the authors "provide no evidence whatsoever that there is any genetic basis to the specific behaviors in their list." Hunley specifically criticizes the last chapter on Ashkenazim for being based on shoddy or fabricated data, and for failing to mention the human suffering caused by pseudoscientific racism. Hunley says the book "fails utterly" to meet the stringent scientific standards of behavioral genetic research.

According to a review in the Financial Times, "Interestingly, the authors make no predictions for our future. And accordingly, biologists – as opposed to social scientists – may not find their thesis all that novel. But it is an engaging book with valuable information about how advantageous genes spread through a population."

In Seed, T.J. Kelleher wrote that "The strength and sheer number of the book’s best sections, however, more than overshadow the wanness and paucity of its worst. Even with its flaws, Cochran and Harpending’s book has provided the best example to date of what E.O. Wilson would recognize as consilient history".

Reporter Ben Schreckinger, writing for Politico in 2017, listed the book among the canon of works which influenced the alt-right's worldview.

Senescence

From Wikipedia, the free encyclopedia

Supercentenarian Ann Pouder (8 April 1807 – 10 July 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence.

Senescence (/sɪˈnɛsəns/) or biological aging is the gradual deterioration of functional characteristics. The word senescence can refer either to cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle.

Senescence is the inevitable fate of all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as Hydra, have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases.

Environmental factors may affect aging, for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body may age at different rates. Two organisms of the same species can also age at different rates, making biological aging and chronological aging distinct concepts.

Definition and characteristics

Organismal senescence is the aging of whole organisms. Actuarial senescence can be defined as an increase in mortality and/or a decrease in fecundity with age. The Gompertz–Makeham law of mortality says that the age-dependent component of the mortality rate increases exponentially with age.

In 2013, a group of scientists defined nine hallmarks of aging that are common between organisms with emphasis on mammals:

Aging is characterized by the declining ability to respond to stress, increased homeostatic imbalance, and increased risk of aging-associated diseases including cancer and heart disease. Aging has been defined as "a progressive deterioration of physiological function, an intrinsic age-related process of loss of viability and increase in vulnerability."

The environment induces damage at various levels, e.g. damage to DNA, and damage to tissues and cells by oxygen radicals (widely known as free radicals), and some of this damage is not repaired and thus accumulates with time. Cloning from somatic cells rather than germ cells may begin life with a higher initial load of damage. Dolly the sheep died young from a contagious lung disease, but data on an entire population of cloned individuals would be necessary to measure mortality rates and quantify aging.

The evolutionary theorist George Williams wrote, "It is remarkable that after a seemingly miraculous feat of morphogenesis, a complex metazoan should be unable to perform the much simpler task of merely maintaining what is already formed."

Variation among species

Different speeds with which mortality increases with age correspond to different maximum life span among species. For example, a mouse is elderly at 3 years, a human is elderly at 80 years, and gingko trees show little effect of age even at 667 years.

Almost all organisms senesce, including bacteria which have asymmetries between "mother" and "daughter" cells upon cell division, with the mother cell experiencing aging, while the daughter is rejuvenated. There is negligible senescence in some groups, such as the genus Hydra. Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells." These planarians are not biologically immortal, but rather their death rate slowly increases with age. Organisms that are thought be biologically immortal would, in one instance, be the Turritopsis dohrnii, also known as the immortal jellyfish. The Turritopsis dohrnii received such a title by having the ability to revert to its youth when it undergoes stress during adulthood. The reproductive system is observed to remain intact, and even the gonads of the Turritopsis dohrnii are existing.

Some species exhibit "negative senescence", in which reproduction capability increases or is stable, and mortality falls with age, resulting from the advantages of increased body size during aging.

Evolutionary theories of aging

Mutation accumulation

Natural selection can support lethal and harmful alleles, if their effects are felt after reproduction. The geneticist J. B. S. Haldane wondered why the dominant mutation that causes Huntington's disease remained in the population, and why natural selection had not eliminated it. The onset of this neurological disease is (on average) at age 45 and is invariably fatal within 10–20 years. Haldane assumed that, in human prehistory, few survived until age 45. Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups, the force of selection against such late-acting deleterious mutations was correspondingly small. Therefore, a genetic load of late-acting deleterious mutations could be substantial at mutation–selection balance. This concept came to be known as the selection shadow.

Peter Medawar formalised this observation in his mutation accumulation theory of aging. "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". The 'real hazards of mortality' such as predation, disease, and accidents, are known 'extrinsic mortality', and mean that even a population with negligible senescence will have fewer individuals alive in older age groups.

Antagonistic pleiotropy

Another evolutionary theory of aging was proposed by George C. Williams and involves antagonistic pleiotropy. A single gene may affect multiple traits. Some traits that increase fitness early in life may also have negative effects later in life. But, because many more individuals are alive at young ages than at old ages, even small positive effects early can be strongly selected for, and large negative effects later may be very weakly selected against. Williams suggested the following example: Perhaps a gene codes for calcium deposition in bones, which promotes juvenile survival and will therefore be favored by natural selection; however, this same gene promotes calcium deposition in the arteries, causing negative atherosclerotic effects in old age. Thus, harmful biological changes in old age may result from selection for pleiotropic genes that are beneficial early in life but harmful later on. In this case, selection pressure is relatively high when Fisher's reproductive value is high and relatively low when Fisher's reproductive value is low.

Adaptive aging

Programmed theories of aging posit that aging is adaptive, normally invoking selection for evolvability or group selection.

The reproductive-cell cycle theory suggests that aging is regulated by changes in hormonal signaling over the lifespan.

Disposable soma

The disposable soma theory of aging was proposed by Thomas Kirkwood in 1977. The theory suggests that aging occurs due to a strategy in which an individual only invests in maintenance of the soma for as long as it has a realistic chance of survival. A species that uses resources more efficiently will live longer, and therefore be able to pass on genetic information to the next generation. The demands of reproduction are high, so less effort is invested in repair and maintenance of somatic cells, compared to germline cells, in order to focus on reproduction and species survival.

Cellular senescence

Cellular senescence
(upper) Primary mouse embryonic fibroblast cells (MEFs) before senescence. Spindle-shaped. (lower) MEFs became senescent after passages. Cells grow larger, flatten shape and expressed senescence-associated β-galactosidase (SABG, blue areas), a marker of cellular senescence.

Cells accumulate damage over time. In particular DNA damage, e.g. due to reactive oxygen species, leads to the accumulation of harmful somatic mutations.

The cellular senescence theory of aging posits that organismal aging is a consequence of the accumulation of less physiologically useful, i.e. senescent cells. In agreement with this, the experimental elimination of senescent cells from transgenic progeroid mice and non-progeroid, naturally-aged mice led to greater resistance against aging-associated diseases. Ectopic expression of the embryonic transcription factor, NANOG, is shown to reverse senescence and restore the proliferation and differentiation potential of senescent stem cells.

In many organisms, there is asymmetric cell division, e.g. a stem cell dividing to produce one stem cell and one non-stem cell. The cellular debris that cells accumulate is not evenly divided between the new cells when they divide. Instead more of the damage is passed to one of the cells, leaving the other cell rejuvenated. One lineage then undergoes cellular senescence faster than the other.

Natural selection can remove damaged cells and prevent their proliferation, counterbalancing the natural tendency for damaged cells to accumulate. However, some cells mutate in ways that escape these control mechanisms. Cancer cells avoid replicative senescence to become immortal. In about 85% of tumors, this evasion of cellular senescence is the result of up-activation of their telomerase genes.

In most multicellular species, somatic cells eventually experience replicative senescence and are unable to divide. This can prevent highly mutated cells from becoming cancerous. In culture, fibroblasts can reach a maximum of 50 cell divisions; this maximum is known as the Hayflick limit. Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length.

Cancer versus cellular senescence tradeoff theory of aging

Senescent cells within a multicellular organism can be purged by competition between cells, but this increases the risk of cancer. This leads to an inescapable dilemma between two possibilities—the accumulation of physiologically useless senescent cells, and cancer—both of which lead to increasing rates of mortality with age.

Chemical damage

Elderly Klamath woman photographed by Edward S. Curtis in 1924

One of the earliest aging theories was the Rate of Living Hypothesis described by Raymond Pearl in 1928 (based on earlier work by Max Rubner), which states that fast basal metabolic rate corresponds to short maximum life span.

While there may be some validity to the idea that for various types of specific damage detailed below that are by-products of metabolism, all other things being equal, a fast metabolism may reduce lifespan, in general this theory does not adequately explain the differences in lifespan either within, or between, species. Calorically restricted animals process as much, or more, calories per gram of body mass, as their ad libitum fed counterparts, yet exhibit substantially longer lifespans. Similarly, metabolic rate is a poor predictor of lifespan for birds, bats and other species that, it is presumed, have reduced mortality from predation, and therefore have evolved long lifespans even in the presence of very high metabolic rates. In a 2007 analysis it was shown that, when modern statistical methods for correcting for the effects of body size and phylogeny are employed, metabolic rate does not correlate with longevity in mammals or birds. (For a critique of the Rate of Living Hypothesis see Living fast, dying when?)

With respect to specific types of chemical damage caused by metabolism, it is suggested that damage to long-lived biopolymers, such as structural proteins or DNA, caused by ubiquitous chemical agents in the body such as oxygen and sugars, are in part responsible for aging. The damage can include breakage of biopolymer chains, cross-linking of biopolymers, or chemical attachment of unnatural substituents (haptens) to biopolymers. Under normal aerobic conditions, approximately 4% of the oxygen metabolized by mitochondria is converted to superoxide ion, which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen, which can, in turn, generate free radicals capable of damaging structural proteins and DNA. Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect that causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes termed oxidative stress are linked to the potential benefits of dietary polyphenol antioxidants, for example in coffee, red wine and tea.

Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species, which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.

Free radicals can damage proteins, lipids or DNA. Glycation mainly damages proteins. Damaged proteins and lipids accumulate in lysosomes as lipofuscin. Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and, thus, hypertension, and vessel wall thickening and reactive tissue formation (atherosclerosis); similar processes in the kidney can lead to kidney failure. Damage to enzymes reduces cellular functionality. Lipid peroxidation of the inner mitochondrial membrane reduces the electric potential and the ability to generate energy. It is probably no accident that nearly all of the so-called "accelerated aging diseases" are due to defective DNA repair enzymes.

It is believed that the impact of alcohol on aging can be partly explained by alcohol's activation of the HPA axis, which stimulates glucocorticoid secretion, long-term exposure to which produces symptoms of aging.

Biomarkers of aging

If different individuals age at different rates, then fecundity, mortality, and functional capacity might be better predicted by biomarkers than by chronological age. However, graying of hair, skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of aging, but success thus far has been limited. Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice.

There is interest in an epigenetic clock as a biomarker of aging, based on its ability to predict human chronological age. Basic blood biochemistry and cell counts can also be used to accurately predict the chronological age. It is also possible to predict the human chronological age using the transcriptomic aging clocks.

Genetic determinants of aging

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding yeast Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies (Drosophila melanogaster). Study of these organisms has revealed the presence of at least two conserved aging pathways.

Gene expression is imperfectly controlled, and it is possible that random fluctuations in the expression levels of many genes contribute to the aging process as suggested by a study of such genes in yeast. Individual cells, which are genetically identical, nonetheless can have substantially different responses to outside stimuli, and markedly different lifespans, indicating that epigenetic factors play an important role in gene expression and aging as well as genetic factors.

The ability to repair DNA double-strand breaks declines with aging in mice and humans.

A set of rare hereditary (genetics) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin. The cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in May 2003. This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

Evolutionary medicine

The bacterium Mycobacterium tuberculosis can evolve to subvert the protection offered by immune defenses

Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory to understanding health and disease. Modern medical research and practice have focused on the molecular and physiological mechanisms underlying health and disease, while evolutionary medicine focuses on the question of why evolution has shaped these mechanisms in ways that may leave us susceptible to disease. The evolutionary approach has driven important advances in the understanding of cancer, autoimmune disease, and anatomy. Medical schools have been slower to integrate evolutionary approaches because of limitations on what can be added to existing medical curricula.

Core principles

Utilizing the Delphi method, 56 experts from a variety of disciplines, including anthropology, medicine, and biology agreed upon 14 core principles intrinsic to the education and practice of evolutionary medicine. These 14 principles can be further grouped into five general categories: question framing, evolution I and II (with II involving a higher level of complexity), evolutionary trade-offs, reasons for vulnerability, and culture. Additional information regarding these principles may be found in the table below.

Human adaptations

Adaptation works within constraints, makes compromises and trade-offs, and occurs in the context of different forms of competition.

Constraints

Adaptations can only occur if they are evolvable. Some adaptations which would prevent ill health are therefore not possible.

  • DNA cannot be totally prevented from undergoing somatic replication corruption; this has meant that cancer, which is caused by somatic mutations, has not (so far) been completely eliminated by natural selection.
  • Humans cannot biosynthesize vitamin C, and so risk scurvy, vitamin C deficiency disease, if dietary intake of the vitamin is insufficient.
  • Retinal neurons and their axon output have evolved to be inside the layer of retinal pigment cells. This creates a constraint on the evolution of the visual system such that the optic nerve is forced to exit the retina through a point called the optic disc. This, in turn, creates a blind spot. More importantly, it makes vision vulnerable to increased pressure within the eye (glaucoma) since this cups and damages the optic nerve at this point, resulting in impaired vision.

Other constraints occur as the byproduct of adaptive innovations.

Trade-offs and conflicts

One constraint upon selection is that different adaptations can conflict, which requires a compromise between them to ensure an optimal cost-benefit tradeoff.

Competition effects

Different forms of competition exist and these can shape the processes of genetic change.

"Diseases of civilization"

Humans evolved to live as simple hunter-gatherers in small tribal bands. Contemporary humans now have a very different environment and way of life. This change makes present humans vulnerable to a number of health problems, termed "diseases of civilization" and "diseases of affluence". Stone-age humans evolved to live off the land, taking advantage of the resources that were readily available to them. Evolution is slow, and the rapid change from stone-age environments and practices to the world of today is problematic because we are still adapted to stone-age circumstances that no longer apply. This misfit has serious implications for our health. "Modern environments may cause many diseases such as deficiency syndromes like scurvy and rickets".)

Diet

In contrast to the diet of early hunter-gatherers, the modern Western diet often contains high quantities of fat, salt, and simple carbohydrates, such as refined sugars and flours. These relatively sudden dietary changes create health problems.

Life expectancy

Examples of aging-associated diseases are atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer's disease. The incidence of all of these diseases increases rapidly with aging (increases exponentially with age, in the case of cancer).

Age-Specific SEER Incidence Rates, 2003-2007

Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90%.

Exercise

Many contemporary humans engage in little physical exercise compared to the physically active lifestyles of ancestral hunter-gatherers. Prolonged periods of inactivity may have only occurred in early humans following illness or injury, so a modern sedentary lifestyle may continuously cue the body to trigger life preserving metabolic and stress-related responses such as inflammation, and some theorize that this causes chronic diseases.

Cleanliness

Contemporary humans in developed countries are mostly free of parasites, particularly intestinal ones. This is largely due to frequent washing of clothing and the body, and improved sanitation. Although such hygiene can be very important when it comes to maintaining good health, it can be problematic for the proper development of the immune system. The hygiene hypothesis is that humans evolved to be dependent on certain microorganisms that help establish the immune system, and modern hygiene practices can prevent necessary exposure to these microorganisms. "Microorganisms and macroorganisms such as helminths from mud, animals, and feces play a critical role in driving immunoregulation" (Rook, 2012). Essential microorganisms play a crucial role in building and training immune functions that fight off and repel some diseases, and protect against excessive inflammation, which has been implicated in several diseases. For instance, recent studies have found evidence supporting inflammation as a contributing factor in Alzheimer's Disease.

Mandatory Palestine

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Mandatory_Palestine   Palestine 1920–...