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more about “Aubrey de Grey Says We Can Avoid Aging “, posted with vodpod
Source: Ted.com

A true maverick, Aubrey de Grey challenges the most basic assumption underlying the human condition — that aging is inevitable. He argues instead that aging is a disease — one that can be cured if it’s approached as “an engineering problem.” His plan calls for identifying all the components that cause human tissue to age, and designing remedies for each of them — forestalling disease and eventually pushing back death. He calls the approach Strategies for Engineered Negligible Senescence (SENS).

With his astonishingly long beard, wiry frame and penchant for bold and cutting proclamations, de Grey is a magnet for controversy. A computer scientist, self-taught biogerontologist and researcher, he has co-authored journal articles with some of the most respected scientists in the field.

But the scientific community doesn’t know what to make of him. In July 2005, the MIT Technology Review challenged scientists to disprove de Grey’s claims, offering a $20,000 prize (half the prize money was put up by de Grey’s Methuselah Foundation) to any molecular biologist who could demonstrate that “SENS is so wrong that it is unworthy of learned debate.” The challenge remains open; the judging panel includes TEDsters Craig Venter and Nathan Myhrvold. It seems that “SENS exists in a middle ground of yet-to-be-tested ideas that some people may find intriguing but which others are free to doubt,” MIT’s judges wrote. And while they “don’t compel the assent of many knowledgeable scientists,” they’re also “not demonstrably wrong.”

“Aubrey de Grey is a man of ideas, and he has set himself toward the goal of transforming the basis of what it means to be human.”

MIT Technology Review


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60 responses to “Aubrey de Grey Says We Can Avoid Aging”


  1. It is good to see BU family members viewing Ted.com we find the talks they post very educational. We extracted this video talk when BT expressed an interest earlier. Obviously thinking about aging? lol


  2. I believe it can be done
    why ?

    because I have always felt that it can be done

    i think that people can control their own predicament. We use a lot less of our brains than we can.


  3. It seems that the fat has left the road and attached itself to these asses brains both ASIBA & AUBREY DE GREY.

    I think I will grow a beard, lose weight and walk bout talking shite so that I can get attention!

    Aubrey de Grey is a man of STUPID ideas, and he has found a new income stream — transforming the basis of what it means to be human


  4. Here is a nice MCQ on this article!

    Aubrey de Grey is
    a- A true maverick and a magnet for controversy
    b- A computer scientist
    c- A researcher
    d- a co- author of journal articles with some of the most respected scientists in the field.
    of biogerontologist
    e- NOT a medical scientist!
    f- known for his penchant for bold and cutting proclamations

    The answer to the above MCQ is obviously E!

    The scientific community doesn’t know what to make of him, because he is not a medical scientist. Here is a buffoon who says he will identify ALL the components that cause human tissue to age, and then designing remedies for each of them, and fore stall disease and eventually push back death.

    Clearly this man does not know very much Pathology or Pathophysiology or Cell or Molecular Biology or Molecular Genetics. No wonder his silly ideas “don’t compel the assent of many knowledgeable scientists.”

    I look foward to falling off my chair with laughter as the BU pontificators wax full of yes wax on this thread.


  5. @ganong

    Did we not read somewhere that 20k has been offered to anyone who can prove the man wrong?

  6. Georgie Porgie Avatar

    David are you saying that because he cant be proven wrong that he is right?

    Are you saying that there is even any merit at all to even try?

    I am here tryinf to decide how I can edit my introduction to Pathology powerpoints to show you the complexities in some of the areas that Ganong has alluded to that pertain to cell injury, cell adaptation and cell death.

    Do you understand the magnitide of identifying the components that cause human tissue to age, far less to design remedies for each of them with a view to fore stalling disease and pushing back death.

    Some folk come on this earth already with the “two hits” in their genes that are required in the two hit hypothesis for the exorbitant cell division that causes cancer.

    There is in my view far more merit in Ganong’s post. I will like Ganong, sit back and read the hypotheses of enlightened BU expositors with great mirth.


  7. What we are saying is simple, if this bearded wonder is spouting rubbish then any post grad should be able to punch many holes in the guys hypothesis…lol.

  8. Micro Mock Engineer Avatar
    Micro Mock Engineer

    … please don’t just sit back GP.

    … so from an engineering perspective, if I were investigating the cause of system failure (apoptosis), my focus would be on those micro-motors that keep the cell in service… kinesins, dyneins and myosins.

    These motors don’t seem to be wearing out due to old age… their control system just seems to shut them down at ‘predetermined’ times.

    A second explanation is that some of the ‘cargo’ (mitochondria, lipids etc.), again at some predetermined time, begin to exceed the carrying load (or stall force) of the motors. Engineers have already calculated the stall forces for your colleagues GP (5 picoNewtons for a kinesin, 1.1 picoNewtons for a dynein motor) 🙂

    A third ‘failure mode’ is that the motors are somehow losing their source of power (hydrolysis of ATP).

    If we can reverse engineer these molecular motors designed by BBE, or alternatively their control system, we just might unlock the secrets of apoptosis.

  9. Micro Mock Engineer Avatar
    Micro Mock Engineer

    … doan worry GP, just now engineers (biomedical, genetic etc.) gonna put you and ganong outta business 🙂


  10. Before you scientists, doctors and engineers knock yourself out you should never forget that as humans we live by a moral code of behaviour. Now messing with the aging process just seems to be conflicting with that moral code.

  11. Micro Mock Engineer Avatar
    Micro Mock Engineer

    wait David… decide which side you on nuh.

    When you immunize your children against certain diseases, what moral code are you in conflict with?


  12. MME,

    Sometime you disappoint me you know!!! I would have thought that this would be ‘cake’ for a man of your intellect….. besides I already explained this…LOL

    The reason why these nano motors appear to have the potential to continue indefinitely is because they were modeled on systems that DO.

    These systems were established by top notch engineers and modeled on their own life systems (BBE created MME in his own image).

    HOWEVER, these MME systems were deliberately designed to be of limited timespan (roughly 70 years)…. more than enough time to achieve the objectives set out for this phase.

    de Gray can therefore be excused for identifying characteristics which suggest that ‘aging’ can be avoided, however he just have not been able to identify the ‘governor’ that has been engineered into the system to limit this possibility.

    I suppose that it IS conceivable that some brilliant mind may discover this limiting factor – but I am not optimistic – besides what is the point of individuals seeking to live extended lifespans? To achieve what?
    Trust Bush tea, if by age 70 you have not achieved the objectives set for real success in this phase of life on earth, it may be best to just go quietly….

  13. The bearded wonder man Avatar
    The bearded wonder man

    Just another smart trying to make a quick dollar from susceptible people.
    Eddie


  14. @MME

    That is why we referred to moral code. Thankfully the majority of the PEOPLE get to decide what we believe is right or wrong. If we left it up to you engineers…

  15. Micro Mock Engineer Avatar
    Micro Mock Engineer

    BT and David,

    wuh wunna really saying doh? Is true I had a few beers earlier, but I didnt think I was drunk till I read David and your last post. Please help me to make intellectual contact with your line of reasoning.

    BT, I agree with you that the motors were modeled on perfect systems (and designed by perfect hands)… that is actually my point… and over the centuries we have been able to extend the average human lifespan by improving our understanding how the machine and the environment around that machine works. That is why the average human lifespan by era has increased as follows (c/o Wikipedia):

    Neanderthal through to Bronze Age – 20
    Classical Greece – 20 to 30
    Classical Rome – 20 to 30
    Pre-Columbian North America – 25 to 35
    Medieval Britain – 20 to 30
    Early 20th Century – 30 to 40
    Current world average – 66.12 (2008 est.)

    I can just picture you, David and GPs ancient predecessors with their ‘four humours’ (GP know what I talkin bout) trying to discourage scientists and engineers a few centuries ago from making the advances that would increase average lifespans over time.

    During which one of those eras should we have stopped tampering with the “moral code” David?

    Look… I going and drink another beer.

  16. Micro Mock Engineer Avatar
    Micro Mock Engineer

    … is a good thing that a small minority, against great odds, continue to make those revolutionary breakthroughs that allow you to do things like sit in comfort at you desk and wax philosophic on the internet David.


  17. Someone should ask Mr. De Grey if Lowdown Hoad’s magic formula, consisting of a regular intake of goat’s milk and Riley’s ham cutters, could play a role in slowing the aging process.


  18. @ The bearded wonder man

    I agree with you that this moron is just another person trying to make a quick dollar from susceptible people.

    @ David
    I don’t know what is the moral code about which you speak, but I believe that the creator God made us. The Psalmist teaches that we are fearfully and wonderfully made, and that we are programmed for 70 years. I agree with you that scientists, doctors and engineers should not try to be in conflict with God’s perfect plan.

    What I am saying is simple: it is hard to punch holes in nothing. One has to hear the details of his hypothesis before you can shred it. The man is talking like Obama in generalities, but no specifics. The man reminds me of the DLP campaign for change; but we are yet to see many specifics of this change- especially in heath!

    @ BT
    You seem to be talking in parables. But I interpret your garbled gobledegooks to mean the same as I have outlined above.

    @ MME
    Immunisation is giving an attenuated form of a disease with the hope that the body will make antibodies to protect the body in the future. I don’t think that is going against the program designed by God. I think that God revealed to Sabin and Salk a principle to facilitate God’s design for immune protection.

    MME biomedical and genetic engineers are limited by the revelation given to them by God himself.

    Let me start by giving you a simple pathology lesson
    • Regardless of the cause, five aspects of the cell tend to be affected by cell injury:
    • 1. Oxygen and oxygen-derived free radicals
    • 2. ATP depletion:
    • 3. Intracellular calcium and loss of calcium homeostasis:
    • 4. Defects in membrane permeability:
    • 5. Irreversible mitochondrial damage:

    Here is a little detail on the above………but its not so easy for laymen to understand.

    • Defects in membrane permeability: early loss of selective membrane permeability leading to overt membrane damage is consistent with all forms of cell injury.
    • Such defects may be due to ATP depletion and calcium modulated activation of phospholipases.
    • The plasma membrane, can also be damaged directly by certain bacterial toxins, viral proteins, lytic complement components, products of cytolytic lymphocytes (perforins), and a number of physical and chemical agents.
    • Once the membrane permeability is affected, the cell loses its ability to maintain homeostasis.
    • Irreversible mitochondrial damage: Mitochondria can be damaged by hypoxia, toxins, etc.
    • If the mitochondria become significantly damaged, the cell loses its capacity to produce ATP and will ultimately die.

    The above is what you refer to as “A third ‘failure mode’ is that the motors are somehow losing their source of power (hydrolysis of ATP). ACTUALLY IT IS THE PRODUCTION OF ATP. BY THE MITOCHONDRIA –THE POWER HOUSE OF THE CELL.
    MME you might have to master the details of the five aspects of the cell affected by cell injury before you start your engineering.

    Good luck.
    de Gray will find that everything can not be done by computer programming.


  19. Free will and apoptosis (or programmed failure?) another contradiction?
    MME attempts to reverse engineer the molecular motors designed by BBE. Then he would become a BBE!

  20. Micro Mock Engineer Avatar
    Micro Mock Engineer

    … ok GP, I’m not sure I understand your ‘justification’ of immunization, but maybe a completely artificial ‘cure’ would help strengthen my point… is the installation of a pace maker “going against the program designed by God”?

    …by the way, I really appreciate that intro to pathology.


  21. @ Green Monkey

    I agree with you that Lowdown Hoad’s magic formula, consisting of a regular intake of goat’s milk and Riley’s ham cutters, could play a role in slowing the aging process, more so than the nonsense De Grey talking.

    @ . MME

    Note that there is a relation of apoptosis to the five aspects of cell injury via capsases.

    Once the cell has got to the stage where these five aspects of cell injury kick in……..its all over! You go to irreversible cell death.

  22. Micro Mock Engineer Avatar
    Micro Mock Engineer

    Devil… its only contradiction if you believe that death is the ‘end’.

    … and reverse engineering BBE’s molecular motors will no more make us BBE’s than mapping the human genome did a few years ago.

    Quite simply, one of the the greatest tributes a creation can pay to its Creator, is a life dedicated to understanding the design.


  23. The Devil

    Free will and apoptosis (or programmed cell death ) are two fifferent things.

    Free will or has to do with man’s choice to obey God. Apoptosis has to do with a program by the body’s cells designed to determine the death of plants animals floweres men etc.

    Apoptosis explains why leaves fall of trees, why branches fall out from your coconut tree, why fruit fall off trees etc

    by the way what is BBE?


  24. But you suggest that either we can remove what is a BBE design feature (apoptosis) which would make us BBEs OR that apoptosis is a flaw which would suggest that the BBE may be a MME!


  25. BBE = THE Big Boss Engineer (you know …Him)

    The free will idea and apoptosis (which I have taken to ultimately determine a person’s lifespan) seem at odds with each other. I have free will but the time I have to execise it is predetermined. (OK my concerns have not crystallised clearly yet).

  26. Micro Mock Engineer Avatar
    Micro Mock Engineer

    Devil,

    I’m not suggesting removing any of BBE’s design features… just understanding them and using our improved knowledge of them to our benefit… as we have been doing for centuries.

    For example, if we understand the mechanics of apoptosis, we may be able to use it for targeted cell destruction e.g. curing cancer.


  27. But Devil, you have it perfectly. BBE designed systems for a specific TIMEFRAME (not exactly X hours but generally between A and B hours)

    In the case of MMEs (GP that is a Micro Mock Engineer – like …us) that time frame is between 0 to 100 years averaging 70 or so. (In the case of this phase of life on earth we can discuss that…)

    Now HC boys like GP would have to find some big word to describe the mechanism of limiting life to around 70 years. If that is apoptosis, so be it.

    HOWEVER, whether or not a MME lives for 20 years, 50 years, 80 years or 120 years is largely a matter of CHOICE of lifestyle, habits and attitudes AND the luck of genetics, AND the luck of chance (like avoiding accidents etc)

    I do not doubt that some bright spark can indeed crack the limiting code and learn exactly what mechanism is limiting us to the approximately 70 years…. but that would no more make us BBEs than the fact that we ‘discovered’ that gravity keeps us on the ground.


  28. MME

    I fully understand your intention to use our knowledge of this design feature for our benefit, but I dont think we can use apoptosis to cure cancer, because there is an apoptosis gene that is involved in the causation of cancer.

  29. Micro Mock Engineer Avatar
    Micro Mock Engineer

    BT,

    that “luck of genetics, and the luck of chance” sounding alot like NATURAL SELECTION yuh… watch yuhself before you an GP fall out again 🙂

    … I am interested in why you stopped at 120 years old. I asked GP before, and he refused to answer. What do you think the limit on our ability to extend average lifespan is? 120 years old?


  30. Surely GP, if you come to understand the mechanism of apoptosis and how it CAUSES cancer we can then use that knowledge to inhibit its action; to provide protection to susceptible cells; to identify and isolate vital components of the apoptosis proces etc….


  31. I don’t know why the story of Babel comes to me at this time.

    What evolutionary advantage would an apoptosis gene have provided?


  32. MME

    I am sorry that I can not transmit the illustrations but if you can follow the below, I can continue to see if I can relate more on the cause of cancer and the apoptosis gene, which is introduced at the end of these poor notes. LOL

    4 major classes of genes are involved in cancer

    1 – growth promoting protooncogenes (gain of function)
    2 – growth inhibiting tumor supressor genes (loss of function)
    3 – genes involved in apoptosis (programmed cell death) (loss of function)
    4 – genes involved in DNA repair (loss of function)

    Changes essential for malignant transformation
    1 – Self-sufficiency in growth signals
    2 – Insensitivity to growth inhibitory signals
    3 – Evasion of apoptosis
    4 – Defects in DNA repair
    5 – Limitless replicative potential
    6 – Angiogenesis
    7 – Ability to invade and metastasize

    Despite wide variations in the gross and microscopic features of individual malignant tumors, they share certain fundamental characteristics that typify their growth and behavior.
    • Nonlethal genetic damage lies at the heart of carcinogenesis.
    • Such genetic damage (or mutation) may be acquired (in somatic cells) by the action of environmental agents, such as chemicals, radiation, or viruses, or it may be inherited in the germ line.
    • The genetic hypothesis of cancer implies that a tumor mass results from the clonal expansion of a single progenitor cell that has incurred the genetic damage; i.e., tumors are monoclonal.
    • This expectation has been realized in the vast majority of tumors that have been analyzed.
    • A cancer is an uncontrolled growth and division of cells that have escaped the normal regulatory mechanisms of the cell cycle.

    • Within our genes…..there are Regulatory mechanisms to control growth and division
    • Proto-oncogene= stimulate cell division
    • Tumor suppressor genes= inhibit division
    • Balance of these two sets of genes- keeps cells dividing normally

    • Mutations that affect regulatory genes are particularly detrimental, because the cell loses ability to control cell division
    • Immune cells
    • Antibodies
    • Cytotoxic T-cells
    • Recognize and destroy cancerous cells displaying markers which are different from normal cells
    • If immune system fails……there is cancer
    • Tumor cells grow and press against normal tissue
    • Finger-like appearance as cancerous cells force their way through tissue
    • Enzymes kill normal tissue
    • Directly move to neighboring tissue
    • Cancerous or tumour or neoplastic cells are said to be transformed.
    • Transformed cells characteristically continue to divide under conditions in which normal cells would become quiescent, i.e. when nutrients or growth factors are depleted from the medium.
    • In cell culture,the cytoskeleton fails to organize correctly and the cells assume a typically rounded appearance and no longer require attachment to substrate to grow.
    Cancers arise because of mutations in the genome of somatic cells as a result of inaccuracies in gene replication or chromosomal rearrangement at mitosis

    • If a result of the mutation is loss of control of cell growth and division, the mutant cell divides more rapidly than the surrounding tissue to form a clone of daughter tumour cells.
    • Tumourigenesis is complex and requires more than one somatic mutation before full transformation of the cell occurs
    • It is established that two classes of normal regulatory genes — the growth-promoting proto-oncogenes and the growth-inhibiting cancer suppressor genes (anti-oncogenes)—are the principal targets of genetic damage.
    • Mutant alleles of proto-oncogenes are considered dominant because they transform cells despite the presence of their normal counterpart.
    • In contrast, both normal alleles of the tumor suppressor genes must be damaged for transformation to occur, so this family of genes is sometimes referred to as recessive oncogenes.
    • There is emerging evidence that a third category of genes — those that control programmed cell death, or apoptosis — are also important in carcinogenesis.Some of the apoptosis-regulating genes function as proto-oncogenes or anti-oncogenes as well.
    • Carcinogenesis is a multistep process at both the phenotypic and genetic level.
    • A malignant neoplasm has several phenotypic attributes, such as excessive growth, local invasiveness, and the ability to form distant mestastases.
    • These characteristics are acquired in a stepwise fashion — a phenomenon called tumor progression.
    • At the molecular level, progression results from accumulation of genetic lesions.
    • With this overview we can address in some detail the molecular pathogenesis of cancer and then discuss the carcinogenic agents that inflict genetic damage.

    Proto-oncogenes, Oncogenes, and Anti-oncogenes
    #55

  33. Micro Mock Engineer Avatar
    Micro Mock Engineer

    “but I dont think we can use apoptosis to cure cancer, because there is an apoptosis gene that is involved in the causation of cancer”.

    GP,

    some of your colleagues disagree…

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1299101

    http://plan2004.cancer.gov/discovery/apoptosis.htm

  34. Micro Mock Engineer Avatar
    Micro Mock Engineer

    Thanks GP.

    I am most iterested in the link you have provided between apoptosis and cancer.

    I have a question about this bullet point:
    “There is emerging evidence that a third category of genes — those that control programmed cell death, or apoptosis — are also important in carcinogenesis.Some of the apoptosis-regulating genes function as proto-oncogenes or anti-oncogenes as well.”

    Everything else you describe about cancer suggests that its ability to RESIST apoptosis is actually the quality that makes it so difficult to control and cure. After all… isn’t the objective of radiation and chemotherapy, to kill those cancer cells that seem to have figured out how to beat apoptosis? From an engineering perspective it is analogous to cell ‘over-speeding’ due to governor (apoptosis) failure.

  35. Micro Mock Engineer Avatar
    Micro Mock Engineer

    … in other words, the problem appears to be linked more to the ability of cancer cells to “block” apoptosis rather than a FAILURE of those genes that control cell death (or apoptosis).

    So, on the one hand, unlocking the secrets of apoptosis will help us in the battle against cancer… and on the other hand, unlocking the secret of how cancer defies “good” apoptosis may help us in the battle against “old age”.


  36. The moral code we live by evolves in the motion of time and place. Keep your seatbelt fastened we do not want any accidents!


  37. David, I like your position yuh!

    When you think about it, one of the best aspects of design of life as we know it is that people DIE!

    ….you could imagine if some people was going to be around for another century?!? Stop GP and MME from this research yuh!!

    Lord have MERCY!!!
    ..no names no lock up….


  38. Most Brits that i care to listen to, I have to read their words, as they are dead. Today’s Brits are a sorry people, who have taken to all manner of hair brain ideas, and activities to garner attention to themselves. They have little left beyond their unique accent, as others who have been invited to live in Britain as a result of their silly believe in multiculturalism have rejected “Britishness” for their own culture. I have place this guy in the same camp as Simon Cowell, and the other Brits judging and hosting some entertainment shows in the US.

    Why would you lead a discussion on slowing the aging process while looking like yours as been accelerated!!

  39. Micro Mock Engineer Avatar
    Micro Mock Engineer

    @ Devil

    You asked “What evolutionary advantage would an apoptosis gene have provided?”

    This is how I understand it so far (GP correct me where I go off track)…

    As GP pointed out in the “Post Kadooment” thread, apoptosis is necessary for our body’s development. It is like a sculptor… shaping tissue and organs by controlling cell growth. The ‘problem’ is, like the energizer bunny it just keeps going and going, continuing to ‘sculpt’ even after we are fully grown – contributing to a process biologists refer to as senescence… ironically it eventually shuts down good cells while seemingly incapable of doing the same to cancer cells which have somehow ‘worked out’ an effective defense.

    The question of evolutionary advantage is one I wish I could answer (… this is just the type of question I would expect from the Devil). Some species of plants and animals, like corals and sea eggs have actually evolved with negligible or even negative senescence – i.e. their mortality decreases with age (as odd as it may sound they grow ‘younger’).Their death is eventually caused by age-independent (or environmental/external) factors. Most species, like us, have evolved such that our mortality is governed by both age-independent AND age-dependent factors (lookup Gompertz-Makeham law)… Anyway, I suspect the answer to your question probably has something to do with SUCCESSION, but I am sure David, BT and GP have better philosophical/religious answers.

  40. Micro Mock Engineer Avatar
    Micro Mock Engineer

    ganong said:

    “It seems that the fat has left the road and attached itself to these asses brains both ASIBA & AUBREY DE GREY”

    “Here is a buffoon who says he will identify ALL the components that cause human tissue to age”

    “Clearly this man does not know very much Pathology or Pathophysiology or Cell or Molecular Biology or Molecular Genetics.”

    Adrian Hinds said:

    “Today’s Brits are a sorry people”

    “Why would you lead a discussion on slowing the aging process while looking like yours as been accelerated”

    GP said:

    “I agree with you that this moron is just another person trying to make a quick dollar from susceptible people.” … this last one concerned me the most, because it is not like GP to make ad hominem attacks rather than deal with the issue… leave that for me and BT 🙂

    I hold no special brief for De Grey, but he is not a moron nor are his claims unscientific. He has a B.A and PhD Cambridge (for computer science and work on the biology of aging respectively). His work on aging has been comprehensively peer reviewed and debated, most notably in MIT’s Technology Review whose judges ruled, after reviewing challenges from leading clinical surgeons and pathologists, that his ideas were “worthy of scientific debate”… http://en.wikipedia.org/wiki/De_Grey_Technology_Review_controversy

    …one of his “scientific” critics accused him in the above link of “drinking too much beer”… so maybe I do hold a bit of a brief for the guy 🙂


  41. @ The Devil

    I personally don’t believe in evolution although I accept that some natural selection or adaptation occurs. I can see how physiological apoptosis might have a role in natural selection. E.g the beneficial differences in the structure and shape of snouts and limbs in wild pigs vs domesticated pigs ie well known.

    Physiological apoptosis is definitely not a flaw as per the examples in the thread in Post Kadooment News.
    Pathological apoptosis is certainly a beneficial design feature when leaves and trees die and are recycled…….although we don’t like it when applied to our loved ones.


  42. @ The Devil
    I personally don’t believe in evolution although I accept that some natural selection or adaptation occurs. I can see how physiological apoptosis might have a role in natural selection. E.g the beneficial differences in the structure and shape of snouts and limbs in wild pigs vs domesticated pigs ie well known.

    Physiological apoptosis is definitely not a flaw as per the examples in the thread in Post Kadooment News. Pathological apoptosis is certainly a beneficial design feature when leaves and trees die and are recycled…….although we don’t like it when applied to our loved ones.


  43. Fellas my PC is giving me goadies, so I have not been able to keep up with the debate in proper time. Let me try to catch up.

    I like the point raised by Adrian Hinds who asked “Why would you lead a discussion on slowing the aging process while looking like yours has been accelerated!!”

    I guess it is because he is so worried about his accelerated ageing! LOL

    I also agree with Bush tea who opined ……..
    When you think about it, one of the best aspects of design of life as we know it is that people DIE!
    ….you could imagine if some people was going to be around for another century?!? Lord have MERCY!!!

    That people die is of course due to the mercy of God, as many are relieved of the pain and suffering of their diseases!

    It would seem that God has modified the apoptosis program so that we live for about 70 years. It is noteworthy that (if you accept the Genesis record in Genesis 5) that in the pre-patriarchal age before the flood men lived routinely for about 900 years, and in the patriarchal age as long as 175 in the case of Abraham. Later the Psalmist advised us that the limit was 70 years.

    Bush Tea you love to sing your song about of CHOICE of lifestyle, habits and attitudes, but apoptosis, genetics, AND the luck of chance (like avoiding accidents etc) probably has a greater say. I know many fit people with great habits etc who died early! By all means adopt proper lifestyle, habits and attitudes BUT DON’T THINK YOU CAN DEPEND ON THEM FOR LONGEVITY. Your apoptosis and p53 genes etc may be programmed for a different out come.

    It might well happen that “some bright spark can indeed crack the limiting code and learn exactly what mechanism is limiting us to the approximately 70 years” but will they be able to alter God’s design? I doubt it.

    With all the great advances we have made in medicine, both the doctors, scientists and their patients die within a certain time frame.They apoptosise!


  44. Bush tea posited
    Surely GP, if you come to understand the mechanism of apoptosis and how it CAUSES cancer we can then use that knowledge to inhibit its action; to provide protection to susceptible cells; to identify and isolate vital components of the apoptosis proces etc….

    That sounds good in theory but will prove very difficult in practice, perhaps because that is just not God’s will!

    We know much about the causation of hypertension, diabetes and other diseases such as Alzheimer’s, but we cant exactly use our knowledge to cure them. At best we can control the disease for a time (probably within the ambit of the time programmed for the individual to fall of as a leaf as stated in Isaiah I think it is).

    The problem with cancer is that often by the time it is discovered it has spread. Then we have top deal with the kinetics of growth. Very difficult. In the development of a cancer it is not as though we can predict when the apoptosis gene will prevail against the others that limit cell growth.

    When it comes to treatment we must realize that Cytotoxic actions of anticancer drugs follow first-order kinetics.
    When we say that destruction of cancer cells by chemotherapeutic agents follows first-order kinetics; we mean that a given dose of drug destroys a constant fraction or proportion of a cell population rather than a constant number of cells.They kill a fixed percentage of tumor cells, not a fixed number.

    The term “log kill” is used to describe this phenomenon. The log-kill hypothesis proposes that the magnitude of tumor cell kill by anticancer drugs is a logarithmic function.

    For example, a 3-log-kill dose of an effective drug will reduce a cancer cell population of 10 to the12 cells to 10 to the 9 (a total kill of 999 x 10 to the 9 cells); the same dose would reduce a starting population of 10 to the 6 cells to 10 to the 3 cells (a kill of 999 X 10 to the 3 cells). In both cases, the dose reduces the numbers of cells by 3 orders of magnitude, or “3 logs.”

    For another example, a diagnosis of leukemia is generally made when there are about 10 to the 9 (total) leukemic cells.

    Consequently, if treatment leads to a 99.999-percent kill, then 0.001 percent of 10 to the 9 cells (or 10 to the 4 cells) would remain.

    This is defined as a five-log kill. At this point, the patient appears asymptomatic; that is, the patient is in remission.

    For most bacterial infections, a five-log (100,000-fold) reduction in the number of microorganisms results in a cure, because the host’s immune system can destroy the remaining bacterial cells.

    However, in treating cancer, because tumor cells are not as readily eliminated, additional treatment is required to totally eradicate the leukemic cell population.

    For this reason, most cancer treatment begins with debulking by surgery and/or radiation in order to initially reduce the neoplastic cell burden before chemotherapy, immunotherapy, or a combination of these treatment modalities is begun.

    Because tumor cells are similar to normal cells, it has been difficult to develop anticancer agents which selectively kill tumor cells without harming normal tissues.


  45. @ . MME
    mapping the human genome did a few years ago only informed us of our genetic makeup

    I agree with you that one of the the greatest tributes a creation can pay to its Creator, is a life dedicated to understanding the design.

    Despite what my optimistic colleagues might think I still think that if we understand the mechanics of apoptosis that this will allow us to cure cancer. See my comments directed to BT.

    I do not know what the limit on our ability to extend average lifespan is. I do not think that is in the preserve of man, any way.

    As a doctor, I have always felt that my role was to try to do what is correct according to the available knowledge, then I have always left the healing the God and the processes he has designed in the body to achieve. Use of medicine etc may facilitate the process to a limited extent.

    MME you asked
    isn’t the objective of radiation and chemotherapy, to kill those cancer cells that seem to have figured out how to beat apoptosis? From an engineering perspective it is analogous to cell ‘over-speeding’ due to governor (apoptosis) failure.

    Whereas the cancer cells seem to have beat apoptosis they actually don’t——–because the result is to deprive the host of its nutrients to support the “rapid growth lifestyle” of the cancer cells. But see the argument on log kill above for difficulty in achieving cures.

    You write “So, on the one hand, unlocking the secrets of apoptosis will help us in the battle against cancer… and on the other hand, unlocking the secret of how cancer defies “good” apoptosis may help us in the battle against “old age”.”

    Sounds good theoretically but I think it will be difficult.

    in the “Post Kadooment” thread, I commented on the benefits of physiological apoptosis.
    Your theory about the conversion of physiological apoptosis to pathological apoptosis is interesting. I am not sure if you have crossed over the line to the realm of de Grey though LOL


  46. MME
    By the way
    Remember that the 7 changes below are essential for malignant transformation
    So more than overcoming the apoptosis gene is needful.
    Changes essential for malignant transformation
    1 – Self-sufficiency in growth signals
    2 – Insensitivity to growth inhibitory signals
    3 – Evasion of apoptosis
    4 – Defects in DNA repair
    5 – Limitless replicative potential
    6 – Angiogenesis
    7 – Ability to invade and metastasize


  47. MME

    This is for you! You will need a few beers to help digest this stuff LOL

    Maybe you can play with this info and might find it interesting
    Im sorry that I cant transmit the illustrations.
    This is stuff I found here and there that helped me to understand the areas in Robbins text on the issues below.
    You will note that the apoptosis gene alone is not involved.

    Proto-oncogenes, Oncogenes, and Anti-oncogenes
    • a.A protooncogene is a normal gene that encodes a protein that stimulates the cell cycle
    • Protooncogenes have important functions in normal cells such as in signaling.They are physiologic regulators of cell proliferation and differentiation which promote cell division when specific signals are present
    • Protooncogenes have multiple roles including that of growth and proliferation.
    • Proteins encoded by protooncogenes function as
    • –growth factor ligands and receptors,
    • –signal transducers,
    • –transcription factors,
    • –cell-cycle components
    • Protooncogenes are potentially oncogenic genes and may be converted into cellular oncogenes (c-oncs) that are involved in tumor development.
    • Protooncogenes are the normal cellular counterparts of the oncogenes. They are usually genes involved in normal cell proliferation.

    When protooncogenes go bad…
    • we get oncogenes!!
    • Protooncogenes are physiologic regulators of cell proliferation and differentiation…..but oncogenes are disturbed protooncogenes (mutated, disregulated…)
    • Mutations which affect the receptor– may be active even in the absence of binding
    • Too much product results in the activation of other genes …………………=> oncogenes.
    • Oncogenes promote autonomous cell growth in cancer cells. They have the ability to promote cell growth in the absence of normal mitogenic signals.

    • -An oncogene is a mutated protooncogene. It encodes an oncoprotein that disrupts the normal cell cycle and causes cancer.
    • Oncogenes are genes that promote autonomous (unregulated) cell growth.
    • Oncogenes are abnormal protooncogenes which promote cell growth in the absence of normal mitogenic signals.
    • Their products are oncoproteins.
    • Oncoproteins resemble the normal products of protooncogenes but lack regulatory control. Their production in the transformed cells becomes constitutive (i.e not dependent on growth factors or other external signals.)
    • Oncoproteins are encoded by oncogenes, and have similar functions as their normal counterparts but endow the cell with self-sufficiency in growth.

    • Oncogenes represent mutations of certain regulatory genes, called proto-oncogenes, which normally stimulate or inhibit cell proliferation and development.
    • 1.Genetic accidents or viruses may lead to the formation of oncogenes.
    • 2. Oncogenes dominate the normal alleles (proto-oncogenes), causing a deregulation of cell division, which leads to a cancerous state.
    • 3. Bladder cancer and acute myelogenous leukemia are caused by oncogenes.

    Oncogenes are
    Mutants of normal proto-oncogenes
    Proto-oncogenes regulate cell growth

    Mutations cause gain of function
    Facilitate malignant transformation
    Stimulating proliferation
    Increasing blood supply of the tumor
    Inhibiting apoptosis
    More frequent in sporadic tumors

    Activation of oncogenes
    • Leads to:
    – Overexpression
    • c-myc – Burkitt lymphoma
    • abl – CML
    – Amplification
    • C-erb B2 (Her2-neu) – breast Ca
    • N-myc – neuroblastoma
    • L-myc – lung Ca
    • Cyclin D1
    • C-myc – breast, lung, ovarian Ca

    Activation of oncogenes by mutations

    Ras was the first isolated oncogene (Rat sarcoma)
    The gene products is a monomeric G protein
    It binds to GTP and activates downstream molecules
    The oncogene and proto-oncogene differed in one aa
    The oncogene is able to signal in absence of GTP
    Ras is the mutational target of many carcinogens

    • Oncogenes were discovered as virally encoded genes that resulted in the loss of host cell growth control when expressed in virus-invaded cells.
    • The proteins encoded by oncogenes are related to the products of non-oncogenic cellular genes, termed proto-oncogenes.
    • The presence of oncogenes in viral genomes is thought to have occurred by recombination of ancestral viral genome with proto-oncogenes in the host cell followed by subsequent mutation into an active oncogene.
    • Expression of cellular oncogenes or the abnormal expression of proto-oncogenes is thought to over-ride normal cell cycle control and lead to uncontrolled cell proliferation.
    • This is clearly an advantage for the virus, which makes use of the host cell machinery for its replication.
    • Oncogenes may arise in cells due to:
    • viral infection and the induction of increased virally encoded proto-oncogene expression under the control of the constitutively active viral promoter
    • viral infection and expression of a virally encoded oncogene activated by mutation
    • chromosomal translocation of cellular proto-oncogenes which place the gene under different transcriptional control, e.g. Burkitt’s lymphoma and chronic myelogenous leukaemia
    • mutation within the coding region of a cellular proto-oncogene, e.g. ras and src oncogenes
    • loss of an inhibition of transformation, i.e. loss of an anti-oncogene or tumour suppressor gene activity, e.g. retinoblastoma susceptibility gene product and p53

    • Most proto-oncogenes encode components of cellular signalling pathways.
    • Their oncogenic potential arises from their ability to mimic growth factors, hormone receptors, G-proteins, intracellular signalling effector enzymes and transcription factors (Fig. 13.16), all of which ultimately lead to a modified control of key regulatory genes.
    • It is noteworthy, for example, that over 30% of all human oncogenes encode tyrosine kinases which normally couple growth factor activation to cell proliferation.

    • Some oncogenes are linked with human cancers
    • In Burkitt’s lymphoma the c-myc gene is translocated from chromosome 8 to chromosome 14, which places the proto-oncogene under the control of an active immunoglobulin locus.
    • In patients with chronic myelogenous leukaemia the c-abl proto-oncogene is translocated from chromosome 8 to chromosome 22. In most patients this results in a novel fusion protein with a constitutively active tyrosine kinase activity.
    • A single base change, leading to a single amino acid substitution, in the ras proto-oncogene results in transformation of the ras gene product into an oncogenic form.

    • Different point mutations transform the ras proto-oncogene by different mechanisms, i.e. either by inhibiting endogenous GTP hydrolytic activity or by altering the rate of guanine nucleotide exchange.
    • Deletion of part of the EGF receptor gene produces the sr-concogene.
    • Inactivation of the tumour suppressor gene product p53 is implicated in 50-60% of all human cancers.
    • A wide range of mutations are found in p53 and different mutations are associated not only with different chemical inducers of cancer or radiation but also with different types of cancer.

  48. Waiting In Vain Avatar

    By the looks of him I would suggest it is not working for him

  49. Micro Mock Engineer Avatar
    Micro Mock Engineer

    Thanks again GP.

    I understand the issues far better than I did a couple days ago.

    You are right… digesting that last post won’t be easy, but I appreciate your patience with a hard-headed engineer. Your point about the apoptosis gene not being solely responsible is well made… but I do suspect it holds the secret to combating cancer and achieving those ‘pre-flood’ lifespans you mentioned… and can you imagine the technological/medical advances that would be brought about by reverse engineering those molecular micro-motors… the possibilities are staggering.

    By the way, “ras proto-oncogene”, isn’t he that guy that sells leather goods in Temple Yard? LOL


  50. This stuff does mek medical students go rong man! It was unknown when I was a student.

    When I was asked to teach it, I spent many hours looking here and there to even get the flow I sent you there. Even so it gave be significant goadies, to even begin to understand it. LOL Let me stick to Biochem and Pharmacology bosie.

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