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"Cell Executioner" Gene
slantyyz writes: "A fascinating and possibly scary scientific discovery -- Toronto scientists have discovered a "chisel of life" gene that kills cells. Apparently this ancient gene, dubbed AIF [apoptosis (death) inducing factor] is found across all forms of life and acts as a cell executioner. While this could have uses in killing cancer cells, it could potentially open the discovery of a true fountain of youth." Nature has more, if you're a subscriber.
Maybe the canadians dont read or something because this "discovery" about cells that kill other cells, apotosis, is very old. The current chancellor of CalTech was working on the research I believe, and the research is now being dont mostly at Cal Tech. Hmmm... I fail to see the point of this post. Alot like that guy that made a report about a bug in BIND that is ages old.
Screw productivity. Life is about enjoyment.
For the Pro-death amongst you; try "potato", I just got three wrinkles on my face today, trying to learn the new dselect. Whatdaya know, after mastering dpkg, i might gray my arm-pits.
Give me a fuckin break. You just posted an /.tard...
article that most of us can't read because
you NEED A PAID SUBSCRIPTION. That's really
/.gay. What the hell, michael? At least
write a detailed summary or something,
Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis and tissue homeostasis. In mammals, release of mitochondrial cytochrome c leads to the cytosolic assembly of the apoptosome-a caspase activation complex involving Apaf1 and caspase-9 that induces hallmarks of apoptosis. There are, however, mitochondrially regulated cell death pathways that are independent of Apaf1/caspase-9. We have previously cloned a molecule associated with programmed cell death called apoptosis-inducing factor (AIF). Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli. Here we show that genetic inactivation of AIF renders embryonic stem cells resistant to cell death after serum deprivation. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies-the very first wave of cell death indispensable for mouse morphogenesis. AIF-dependent cell death displays structural features of apoptosis, and can be genetically uncoupled from Apaf1 and caspase-9 expression. Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis.
Programmed cell death (PCD) is a fundamental property of all multicellular organisms. It is crucial for plant and animal development, insect and amphibian metamorphosis, organ morphogenesis, tissue homeostasis, ageing, and the removal of infected or damaged cells1. The biochemical and ultrastructural features of apoptosis are highly conserved throughout the evolution of multicellular animals1-4. PCD has been linked to the CED9/Bcl-2, CED4/Apaf1 and CED3/caspase-9 genes that are essential for PCD in Caenorhabditis elegans and vertebrates5-8. In response to death stimuli, mitochondrial membranes are permeabilized9, 10, and cytochrome c is released from mitochondria3, 11, 12 and associates with Apaf1 and pro-caspase-9 to trigger a caspase activation cascade that culminates in cell death characterized by apoptotic morphology7, 13-15. Failure to invoke appropriate cell death can result in cancer or autoimmunity, whereas increased PCD can lead to degenerative processes such as immunodeficiency and neurodegenerative disease16.
Although the cytochrome c/Apaf1/caspase-9 apoptosome is essential for several PCD pathways, cells deficient in these molecules can still die3. Indeed, cytochrome c, apaf1 and caspase-9 knockout mouse embryos undergo normal, albeit delayed, morphogenesis17-21. Moreover, cell lines derived from these mutant mice are not uniformly resistant to death stimuli, but instead undergo PCD in a manner specific to both cell type and death signal19. It has also been shown that Bcl-2 preserves the integrity of mitochondrial membranes and protects cells from death independently of Apaf1 and caspases, implying that Bcl-2 interferes with two different mitochondrion-dependent death effector cascades22, 23. Thus, a death effector system other than cytochrome c/Apaf1/caspase-9 must be able to induce PCD.
We previously cloned apoptosis-inducing factor (AIF), which, like cytochrome c, is normally present in the mitochondrial intermembrane space and is released in response to death stimuli24, 25. Extramitochondrial targeting of AIF, micro-injection of recombinant AIF protein into cells, or addition of AIF to isolated nuclei leads to the generation of apoptotic phenotypes, such as chromatin condensation and phosphatidylserine exposure on the cell surface24. AIF has also been implicated in the control of apoptosis in syncytia induced by the HIV type-1 envelope glycoprotein26, indicating that AIF may be involved in the pathogenesis of HIV infections. But although AIF can induce certain aspects of cell death in cultured cells, whether it is essential for PCD in vivo remains unresolved. Moreover, AIF has never been linked to PCD at the genetic level.
To explore the role of AIF in the control of PCD during animal development, we disrupted the mouse aif gene by homologous recombination. We report here that AIF is essential for the first wave of PCD required for embryonic morphogenesis and cavitation. Moreover, inactivation of AIF renders embryonic stem cells resistant to cell death after serum starvation. These results provide the first genetic evidence of a second, mitochondrially regulated cell death pathway in mammalian cells that is critical for morphogenesis and PCD after withdrawal of survival factors.
Gene targeting of aif in embryonic stem cells The murine aif gene was ablated in embryonic stem (ES) cells using a targeting vector that deleted exon 3, corresponding to the amino terminus of the mature protein (nucleotides 247-346, amino acids 83-115). Three independent aif-targeted ES cell clones were obtained. Because the aif gene maps to the X chromosome24, mutation of one aif allele resulted in a complete knockout in XY male ES cells and absence of aif expression by northern and western blotting (see Supplementary Information Fig. 1). As a control for changes to ES cells during G418 selection, ES cell clones were isolated in which the neomycin resistance cassette had integrated randomly into the genome (aif neo/Y).
Three independent aif -/Y ES cell clones were injected into C57BL/6 blastocysts to generate chimaeric mice, and into rag1-/- blastocysts for lymphocyte reconstitution27. Whereas all parental wild-type ES cell clones (aif +/Y) and all aif neo/Y ES cell clones could contribute to adult tissues in chimaeric mice and reconstitute T- and B-cell lineages in rag1-/- mice, we failed to observe any chimaerism using all three aif -/Y ES cells clones. Using in vitro ES cell differentiation and formation of teratocarcinoma-like tumours in vivo28, however, aif -/Y ES cell clones differentiated into cells from all three germ layers, including cartilage, muscle, neuronal tissue, epithelium, B cells, myeloid and erythroid cells (see Supplementary Information Fig. 1)29. Thus, aif -/Y ES cells retain their capacity to differentiate into cells from all three germ layers.
aif -/Y ES cells are resistant to growth factor deprivation The aif -/Y ES cell lines exhibited normal proliferation in vitro. Unlike cytochrome c-/-, apaf1-/- and caspase-9-/- ES cells17, 19, 21, aif -/Y ES cell lines displayed normal susceptibility to death, which was preceded by the dissipation of the mitochondrial transmembrane potential (m), in response to staurosporine, etoposide, azide, tert-butylhydroperoxide (Fig. 1a), anisomycin or ultraviolet irradiation (data not shown). This normal susceptibility to cell-death induction was observed both in the absence and in the presence of the pan-caspase inhibitor Z-VAD.fmk (Fig. 1a). Whereas serum withdrawal results in cell death of aif +/Y, aif neo/Y and apaf1-/- ES cells23, all three aif -/Y ES cell lines largely conserved their viability and normal mitochondrial membrane integrity (m) when cultured in the absence of serum (Fig. 1b). Moreover, in the presence (but not the absence) of Z-VAD.fmk, aif -/Y ES cell lines failed to die in response to the pro-apoptotic agent vitamin K3 (menadione) (Fig. 1b). Thus, AIF is rate-limiting for some pathways of death induction. In particular, aif -/Y ES cells are resistant to death after growth factor withdrawal.
AIF is essential for cavitation of embryoid bodies The absence of overt chimaerism in whole organisms, yet the apparently normal differentiation potential of aif -/Y ES cells in vitro and in vivo, suggested that AIF might be required for normal PCD during early embryonic development. PCD occurs throughout mammalian development, beginning with apoptosis of the initially solid embryonic ectoderm to generate the proamniotic cavity30. This early developmental process can be mimicked in vitro by culturing aggregates of ES cells in the absence of leukaemia inhibitory factor and feeder cells31. Under these culture conditions, ES cells form undifferentiated cell aggregates that develop into simple embryoid bodies (EBs), defined as multicellular aggregates containing an outer layer of endodermal cells and a solid core of undifferentiated ectodermal cells (Fig. 2a, left). The inner cells of simple EBs subsequently undergo PCD to form cystic EBs (Fig. 2a, top centre), a process called cavitation. As cystic embryoid bodies are cultured in vitro, the cavity expands (Fig. 2a, top right). The removal of cells of the inner core to form a cavitated or cystic EB is the first known wave of PCD during mouse morphogenesis30.
When aif -/Y ES cells were tested in the EB formation assay, they were able to form simple EBs at frequencies and with kinetics comparable to those of aif +/Y and aif neo/Y controls (Fig. 2). But whereas a significant proportion of aif +/Y and aif neo/Y EBs underwent cavitation to form cystic EBs, EBs from all three differentiated aif -/YES cell lines exhibited a complete block in cavitation (Fig. 2a, b; and Supplementary Information Fig. 2). As cavitation is essential for the initiation of gastrulation and thus subsequent steps in embryogenesis32, defective cavitation by aif -/Y EBs probably explains the inability of aif -/Y ES cells to lead readily to adult tissue in chimaeric mice.
AIF controls PCD during early morphogenesis Impaired cavitation might be due to either increased proliferation and/or impaired PCD of the cells that form the inner core. To investigate whether EB cell proliferation was increased in the absence of AIF, we examined BrdU (5-bromodeoxyuridine) incorporation by wild-type and aif -/Y EBs. Although aif -/Y EBs displayed abnormal morphology (Fig. 3a, left) and histology (Fig. 3b, left), no evidence was obtained for increased proliferation of the inner cells of aif -/Y EBs at day 3, day 5, or at any later time point as compared with wild-type EBs (data not shown). To assay for PCD, the inner cells from wild-type and aif -/Y EBs were analysed by DAPI (4',6-diamidino-2-phenylindole dihydrochloride) staining to detect chromatin condensation (Fig. 3c, left) and by assays for in situ caspase-3 activation (Fig. 3d, left). Massive apoptosis was observed in the wild-type EBs, but no signs of cell death were found among the inner cells of aif -/Y EBs. These results indicate that impaired cavitation in aif -/Y EBs is not caused by enhanced proliferation but is due to a failure of inner cells to undergo PCD.
The outer endoderm cells have been suggested to provide death signals to inner cells required for cavitation30; however, histological and electron microscopy analyses showed that simple aif -/Y EBs do not lack endodermal tissue. Furthermore, aif -/Y EBs expressed the endoderm-specific32, 33 markers BMP2, BMP4, GATA-4, -fetoprotein and HNF-4 (data not shown). To establish that the defects of aif -/Y cells are autonomous to inner cells, we generated chimaeric EBs by mixing aif -/Y and wild-type ES cells expressing a lacZ reporter (aif +/Y; lacZ) (Fig. 4a). Although cavitation was partially rescued in these chimaeric EBs (Fig. 4b), cell death was restricted to wild-type (blue) inner cells (Fig. 4b-e). Our mixing experiments also showed that aif -/Y cells can differentiate into columnar epithelium (Fig. 4f). These results indicate that impaired cavitation in aif -/Y EBs is not caused by defective endoderm formation. Instead, impaired cavitation is due to an intrinsic failure of AIF-deficient inner cells to undergo PCD.
Apaf1 and caspase-9 are not required for cavitation The death of inner cells in wild-type EBs was found to be accompanied by the activation of caspase-3 (Fig. 3d, left), an effector caspase downstream of the cytochrome c/Apaf1/caspase-9 apoptosome. We therefore explored the contribution of Apaf1 and caspase-9 to cavitation by analysing the development of EBs from apaf1-/- and caspase-9-/- ES cells17, 19. Genetic inactivation of the apaf1 and caspase-9 genes abolished caspase-3 activation (Fig. 3d, right). However, loss of Apaf1 or caspase-9 expression had no apparent effect on cavitation (Fig. 3a, b; and Supplementary Information Fig. 3) or the death of inner cells (Fig. 3c). The kinetics and extent of cells that undergo chromatin condensation were comparable among wild-type, apaf1-/- and caspase-9-/- EBs (n = 5 per group). Adding the broad-spectrum caspase inhibitor z-VAD.fmk to developing wild-type EBs also failed to block cell death and subsequent cavitation. These results show that the PCD required for EB cavitation can occur in the absence of caspase-3 activation and can be genetically uncoupled from Apaf1 and caspase-9.
We next examined the intracellular localization of AIF in EBs and the effect of mutations of apaf1, caspase-9 or aif on AIF and cytochrome c mobilization. In response to death stimuli AIF translocates from the mitochondria to the nucleus, whereas cytochrome c localizes to the cytosol24. AIF (Fig. 5a, red colour) was found to translocate from the mitochondria to the nucleus (green DNA stain) in inner cells, but not in the outer endodermal cells of wild-type, apaf1-/- and caspase-9-/- EBs. Cytochrome c was also released from mitochondria of wild-type, apaf1-/- and caspase-9-/- inner cells (Fig. 5b). There was no detectable cytochrome c translocation from mitochondria to the cytosol in inner cells of aif -/Y EBs, indicating that mitochondrial membranes fail to permeabilize. This result is consistent with the failure of aif -/Y inner cells to activate caspase-3 (Fig. 3d), a defect that presumably results from deficient assembly of the apoptosome. These findings indicate that AIF acts upstream of cytochrome c and independently of the cytochrome c/Apaf1-triggered caspase activation cascade during cavitation.
AIF-regulated PCD has characteristic features of apoptosis It has been reported that cell death of apaf1-/- and caspase-9-/- ES cells in response to ultraviolet radiation exhibits the morphological features of necrosis rather than apoptosis19, 23. To establish whether AIF-controlled cell death in EBs has the ultrastructural characteristics of apoptosis, inner cells from wild-type and aif -/Y EBs were compared using electron microscopy. Dying inner cells in wild-type EBs displayed typical apoptotic morphology (Fig. 6a), including the presence of chromatin condensation, plasma membrane blebbing, formation of apoptotic bodies, and a preserved ultrastructure of cytoplasmic organelles. Inner cells from aif -/Y EBs retained a healthy phenotype (Fig. 6b). Intriguingly, the inner cells from both caspase-9-/- and apaf1-/- EBs exhibited typical features of apoptosis, such as intact nuclear and plasma membranes, chromatin condensation (Fig. 6c-f, asterisks), plasma membrane blebbing (Fig. 6c, d, arrows), formation of apoptotic bodies (Fig. 6e), and preserved ultrastructure of mitochondria (Fig. 6c, f, solid arrowheads) and rough endoplasmic reticula (Fig. 6c, f, '>'). These features were similar to those in wild-type inner cells.
Consistent with the absence of caspase-3 activation, caspase-9-/- and apaf1-/- EBs do not manifest an advanced pattern of chromatin compaction (Fig. 6a). Instead, a peripheral type of chromatin compaction predominated (Fig. 6c-f). Thus, with the exception of caspase-dependent advanced chromatin compaction, the AIF-regulated pathway of PCD required for embryonic cavitation exhibits classical ultrastructural features of apoptosis and is independent of the Apaf1/caspase-9-mediated PCD pathway.
Discussion In C. elegans, genetic evidence suggested that apoptosis is strictly dependent on caspase activation5. We provide genetic evidence here that not all apoptosis of mammalian cells is dependent on caspases, and that an AIF-dependent, caspase-independent PCD pathway exists that is crucial for cell death following growth factor deprivation and early mammalian development.
AIF and mitochondrial control of apoptosis. Numerous reports have shown that caspase inhibition prevents mammalian cell death or blocks the acquisition of morphological and biochemical characteristics of apoptosis34. Moreover, mutational analyses of cytochrome c (ref. 21), caspases19, 20 and Apaf1 (ref. 17) showed that these molecules contribute to apoptosis in a manner specific to both cell type and death signal. Similarly, aif -/Y ES cells, unlike apaf1-/- and caspase-9-/- ES cells, are sensitive to various apoptotic stimuli, such as staurosporine, anisomycin, ultraviolet irradiation and etoposide. However, aif -/Y ES cells are resistant to serum withdrawal and AIF is essential for the first wave of cell death during mouse morphogenesis. These data indicate the coexistence of two separate pathways linking the mitochondria to apoptosis, one that requires AIF and the other that relies on caspase activation.
The results of our study provide definitive genetic evidence that AIF inactivation abolishes all signs of cell death in early morphogenesis, including the mitochondrial release of cytochrome c. Moreover, AIF is a rate-limiting factor of ES cell death induced by menadione (only if caspases are simultaneously blocked) or by serum withdrawal (independently of caspase inhibition), indicating a stimulus-dependent contribution of AIF to the apoptotic cascade. The exact hierarchies and communication between AIF and the cytochrome c/Apaf1/caspase-9 apoptosome in cell-type- and death-signal-specific PCD remain to be determined.
Morphogenesis of multicellular organisms. PCD is essential during early animal development for the sculpting of digits, the palate and the eyes, the formation of hollow organs and the neural tube, and the generation of sexual organs1. In early mouse embryos, the proamniotic cavity is formed by the death of the ectodermal cells in the core of the developing embryo30. Thus, PCD is an integral part of morphogenesis and metamorphosis at all stages of animal development. Because developmental PCD exhibits the structural hallmarks of apoptosis, the finding that C. elegans bearing mutations of their caspase (CED-3) or Apaf1 (CED-4) orthologues have normal lifespans2 was originally surprising. Moreover, morphogenesis and organ sculpting are also normal in cytochrome c, apaf1 and caspase-9 knockout mouse embryos, albeit delayed17-21. These observations pointed to the existence of another PCD pathway that can compensate for the absence of caspase-dependent apoptosis and that is highly conserved through evolution. As AIF messenger RNA and protein expression can be detected throughout murine embryogenesis and in all developing organs (see Supplementary Information Fig. 4), it is likely that AIF contributes to morphogenesis at later stages of embryogenesis.
We have shown that the genetic inactivation of AIF abolishes the first wave of developmental cell death occurring during early mouse embryogenesis. Assuming that ontogenesis recapitulates phylogeny, it is tempting to speculate that AIF represents a pathway of apoptosis that predates the caspase pathway. Whereas AIF homologues have been found in all metazoan phyla35, no evidence for caspases has been reported in plants, fungi or unicellular organisms such as the Trypanosoma cruzi epimastigote, all of which can nevertheless undergo PCD1. We propose that AIF and the AIF-regulated cell death pathway constitute an ancient and conserved process required for the morphogenesis of multicellular organisms. The identification of the molecules involved in this PCD pathway and their genetic and functional characterization should yield new insights into the basic physiology of cell death, and might allow us to develop strategies for the modulation of the cell death machinery.
Methods aif-deficient ES cells and chimaeric mice The aif gene was cloned from a 129/SVJ mouse genomic library using a mouse aif probe (nucleotides 247-346). A targeting vector (600 base pairs short arm, and 6 kilobases long arm) flanking a PGK-Neo cassette was electroporated into male E14K ES cells. ES cell colonies resistant to G418 (300 g ml-1) were screened for homologous recombination by polymerase chain reaction (sense primer, 5'-GGGATTAGATAAATGCCTGCTCTT-3'; antisense primer, 5'-CCCCCAAACTTATATCAGCCTACCTTC-3'). Recombinant colonies were confirmed by Southern blotting of HindIII-digested genomic DNA hybridized to a flanking probe. Total RNA was extracted from aif -/Y ES cells and subjected to northern blotting using full-length AIF complementary DNA. Absence of AIF protein in aif -/Y ES cells was determined by western blotting using an antibody reactive to residues 151-200 of murine AIF24. Antibodies to Apaf1 (Upstate Biotechnology) and actin (Sigma) were used as controls. To test contribution to adult tissues, aif -/Y ES cells were injected into blastocysts from rag1-/- mice27 and C57BL/6 mice to generate chimaeric animals. Mice were maintained at the animal facilities of the Ontario Cancer Institute in accordance with institutional guidelines. Equivalent results and phenotypes were obtained for three independent aif -/Y ES cell clones. apaf1-/- and caspase-9-/- ES cells have been described17, 19.
ES cell differentiation Parental wild-type aif +/Y, three aif -/Y ES cell clones and ES cell clones in which Neo was randomly integrated (aif neo/Y) were cultured under conditions promoting differentiation into EBs29, 36. Chimaeric EBs were generated using aif -/Y ES cell clones (lacZ-negative) and aif +/Y ES cells constitutively expressing lacZ (aif +/Y; lacZ). The aif +/Y; lacZ ES cell clone contains a randomly integrated copy of the lacZ gene fused to the chicken -actin promoter37. For colony assays, single EB cell suspensions were replated in methylcellulose. Blood islands were detected using benzidine. ES cells were further differentiated into primitive mesodermal cells by co-culture with OP9 bone marrow stromal cells for 5 d. Single-cell suspensions from these cultures were either used for FACS analysis of Flk1+ hemangioblasts or replated onto OP9 cells and grown for an additional 5-12 d. Colonies were counted 10-14 d later and stained with Wright-Giemsa to analyse morphology, and with anti-CD45, CD11b, CD19 and TER-119 monoclonal antibodies38. In vivo tumour formation of ES cells in athymic nu/nu mice and detection of differentiated tissues have been described 28.
Quantification of cell death We cultured ES cells in the presence of 10% fetal calf serum and leukaemia inhibitory factor. Cell death was induced by addition of staurosporine (2 M, 24 h), etoposide (100 M, 24 h), sodium azide (15 M, 48 h), tert-butylhydroperoxide (200 M, 48 h) or menadione (150 M, 24 h), or by serum withdrawal (0%, 72 h), in the presence or absence of Z-VAD.fmk (50 M). Death was quantified by staining with propidium iodide (PI; 5 g ml-1) and DiOC6(3) (40 nM).
Immunostaining and in situ procedures For in situ localization of AIF and cytochrome c (ref. 25), paraformaldehyde-fixed EBs were stained with rabbit antiserum raised against residues 151-200 of AIF, or anti-cytochrome c monoclonal antibody (clone 6H2.B4, Pharmingen) followed by PE-conjugated goat anti-rabbit IgG (anti-AIF) or PE-conjugated goat anti-mouse IgG (anti-cytochrome c). Cells were counterstained with 10 nM Sytox Green (Molecular Probes). Staining was detected by confocal scanning fluorescence microscopy. Electron microscopy and in situ DAPI staining to detect chromatin condensation were as described19. Activated caspase-3 was detected using an antibody specific for the cleaved (active) form of caspase-3 (New England BioLabs). In situ hybridization of murine embryos at distinct stages of development was done using sense and antisense probes from murine aif cDNA (nucleotides 456-1607).
So your heart cells may really be apoptosing in a stroke or heart attack. The question then is: will it really help to prevent this? Maybe, if medical attention can save the cells if they can be stopped from committing suicide, but if not, blocking apoptosis will just lead to necrosis and lots of enzymes, damaged DNA, and other cellular crud floating around.
Every time a new technology is discovered/invented to do with people there's the silly bastard reaction that we're messing with nature (the awful unsaid meme being that humans are outside nature). Everything we do impacts on what would have happened without our efforts - we impose our will on others and animals and the universe. When we save a beached whale it probably would have died - but I think we did a good thing (although blowing it up is quite entertaining too - and i'm a vegetarian). So, really, it's not about messing with nature (the very idea of that reeks of a religious 'greater plan') but instead about what benefits the world. Medicine has proven to be a good thing - as has surgery, yet because these are ingrained we don't consider them "unnatural" anymore. Yet they extend life from an average of 40yrs to perhaps 80. Screw this 'good and short life' crap - Billy Corgan was right, it's not live fast die young, it's live fast live long.
Does living a few years longer benefit the world? Yes, it does.
Isn't that a Chinese curse?
We give them all tiny little swords and declare, "There can be only one!"
It's not enough to bash in heads, you've got to bash in minds. - Captain Hammer
Death defines life ; and it's the very fact that we have a finite time in this body that gives us the drive to squeeze the most out of it while we still have it.
Of course, the same factors create some of the stupidity we see today. Nobody in charge seems to be worried about global warming. This is in part because they and everyone they know will be safely dead before things progress to 'Damnation Alley' like proportions. If they thought they might have to live in the future they're creating (and suffer like everyone else), they might be more careful to create a good one.
There is no question that extending the human lifespan would change things. Some problems would go away, others would take their place.
Just increasing the quality of late life will have an impact. We will then have people in their seventh and eighth decade who have the energy and vigor to participate more fully in society. Some will be deeply set in their ways, others will have decided that most social 'problems' which plague their younger collegues really don't matter very much. For example, would a person who had actually seen civilization survive the 'terribly destructive' influence of the novel, radio, television, Elvis, The Beatles, etc. be as concerned about violent video games as the numbskulls in Washington today? (Yes, all of those things were at one time considered terribly destructive and decried as the downfall of civilization by some group or another).
The question is, who would 'win', those dedicated to the status quo, or those who had already seen too many changes to care about the status quo anymore?
Current estimates place the number of people that have ever lived at a little over 100 billion people. There's about six billion around today, which would imply that closer to 94% have been and gone.
Just out of interest, how old are you?
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That wouldn't work: gene transfer is always extremely inefficient, maybe 1 in a hundred or in a thousand cells will take up and incorporate the gene correctly. Those few cells will then apoptose soon after, leaving the rest of the cancer cells multiplying happily.
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But wait a minute, I am already immortal, as far as I remember, I have always been alive.
Black holes occur when God divides by zero.
Of all the people that have ever lived, only half have died. So you may be overstating your case.
Source: some smithsonian natural history exhibit or other.
Damn, my chances have just gone down a lot. Thanks for the correction though.
Indeed, but a lot of effort tends to be focused on the leading killers. So if all natural/disease based death were gone, accidents would be next on the chopping block.
New cars would make today's volvos look like deathtraps. Buckets would have little sensors that would detect drowning, and open drain holes. Ladders would automatically drill themselves into the floor or ground.
Accidents would still kill, but that 600 number would slowly drift ever higher.
Biologically there is something quite right with it. There is a theory that old age death is very good for a species. It can't really be tested at this time, of corse. The closest you can do is take a genetic programming package, find a problem it can solve, and then change it to remove old age death. Then see if it can still solve it, and if it can if that takes more generations or not. My meager experiments with the "simplified ants looking for food" problem shows a huge increase in the number of generations needed to find the solution. But don't take my word for it, it's a pretty easy experiment, go try it. (note you still kill off the bad performers, you only let the "old" ones live if they are in the top few percent)
Socially it looks like old age death is a good idea. Most mathmations (for example) make their good discoveries early, and then don't do a whole lot. Or so I have been told. Plus think of the divorce rate if we don't have the death escape hatch 50% of marriages use :-)
All kidding aside, for social effects the only place I have seen them investigated is science fiction, and the results vary quite a bit. Many of those societies I wouldn't enjoy as much as this one, except of corse, I would have far more time to enjoy them....
Economically losing old age death would be a disaster if we didn't also lose old age (forget our current social security problems, if the avg. age shot up to 150 we would be sunk!). If we lost old age as well things wouldn't be as bad, but the increasing population would make jobs a bit scarce (unless birth rates dropped dramatically).
Personally, I would love to live forever (assuming I get to do it in fairly good health, and in a more or less normal mental state). It only causes a problem when we all get to do it :-)
I can only think of one thing: "Soylent green is made of people" Immortality is not for a rapidly reproducing species. // yendor
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It could be coffe.... or it could just be some warm brown liquid containing lots of caffeen.
If cells DID NOT NEED to die, this gene would not exist.
Well, nobody's suggesting that this gene should be eliminated -- just controlled a bit better. The purpose of apoptosis is to kill cells that appear to be abnormal (i.e. mutated cells and tumor cells). But the system is hardly perfect and many perfectly good cells are killed while many tumor cells are allowed to live.
The fact is that natural selection doesn't work that well to improve such a system because generally cancer occurs to old people past child-bearing age and so there is no selective pressure.
Without the gene programmed cell death cannot occur and growth cannot proceed beyond the embronic stage
Cell death for development is important but it isn't the primary function of apoptosis or AIF in general.
..sigh..
There's no time for us
There's no place for us
What is this thing that fills our dreams
Yet slips away from us?
There's no chance for us
It's all decided for us
This world has only one sweet moment
Set aside for us.
Who wants to live forever?
Who wants to live forever
Oh_______ when love must die?
Touch my tears
With your lips
Touch my world
With your fingertips
And we can have forever
And we can love forever
Forever....
Forever....
Forever... is our today.
Who wants to live forever?
Who wants to love forever?
Who dares to love forever?
Oh________
Who waits forever anyway?
(I would attribute this properly, but any self-respecting person should know it..)
It doesnt prevent car crashes, cancer...
Actually, the same technology might be used to prevent cancer by selectively killing off only cancer cells... but I get your point.
Apoptosis is a biological term for "cellular death". A few years ago Byte magazine published this article about a product called Apoptosis that unleashes "cellular death" on cellular phones. It supposedly disconnects cellular phone calls within a short distance. There were certainly times when people talking loudly in public places on their cellphone made me wish I had one of those.
I suspect this product was a hoad, but back in the days of analog cellphones it was actually very easy to build a device that does this: the frequency spacing between the transmit and receive frequency was exactly 40MHz. You could build a cheap device that receives the strongest signal around, mixes it with a 40MHz oscillator and transmits the result back. Multipying two sines results in the sum and difference of their frequencies - one of them will jam the receiver side of the phone very efficiently.
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Stop worrying about the risks of nuclear power and start worrying about the risks of not using nuclear power.
(oops, hoad->hoax)
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Stop worrying about the risks of nuclear power and start worrying about the risks of not using nuclear power.
I don't believe that were we to achieve immortality is would result in a Human Race that was any happier than it is today. Death defines life ; and it's the very fact that we have a finite time in this body that gives us the drive to squeeze the most out of it while we still have it. So Death is a very important part of the Human experience and we should accept that.
:-)
What is of interest and importance to me is the quality of life and in particular, health, as we get older. I remember seeing a documentary on TV about a treatment given to OAP's derived from embryo research (I don't remember the species or nature of the drug) but the net effect was increased energy, hardening of the bones (curing osteoporosis) and thickening of the skin to levels more common in youth. If science can deliver a way to keep me more alert and 'bouncy' until it's my time to pass on, then I'll be a very happy man in deed.
Who wants to live forever
Macka
ok Wowbagger.
Credit Mr Adams why doncha?
Why is it that many people who claim to support standards have such atrocious spelling and grammar?
You should either stop getting your statistics from fantasy novels, or get a dictionary with a better definition of "half".
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A lifespan specified only by accidents should have a Poisson probability distribution. The probability of your demise as a function of time is a decreasing exponential with appropriate scaling. While there will be an "expected" lifespan, this will be very different from today's more bell-curve-like distribution, with most people dying much younger and a lucky few living a very long time, and very few people dying exactly at 600 years old.
WWJD for a Klondike Bar?
I read once that even if all natural and disease based causes of death were eliminated, the average human would only live about 600 years. The reason? Accidents.
One might argue that medical science's ability to clean up after our accidents will improve with time, but I doubt it is every going to figure out a way to put our brains back together if they are splattered all over the road in the course of being struck by a car.
So there is an upper bound to our life span even if we are technically 'immortal'.
-josh
Uhm...did you read the article? AIF acounts for natural cell death. All cells must die at some point. Besides, think of how a virus works. IIRC a virus takes over a host cell and modifies it so that it produces more viruses. Eventually this host cell will die, killing the virus production factory. Now think about what would happen if said cell didn't die; it would continue to produce more viruses indefinately. Sure your immune system would be able to kill said cells eventually, but it would need to do so for the rest of your life, or until the cell died due to some other circumstances.
AIF would not be usefull in fighting standard viruses. It COULD be usefull in fighting cancer by telling the cancer cells to self destruct (which would be much less invasive than physically removing the cancerous tissue). Then again, one slight mistake and you could easily kill the patient, either by making all of their cells die immediately, or making them all live forever, which (I think) would make the patient's entire body cancerous. In short, AIF seems like a very sharp double edge sword.
-matt
Just FYI, rats bred (well that were attempted to be bred) without the AIF gene did not grow beyond the embryotic stage. I'd say that is pretty good evidence for this gene being required.
-matt
I'm obsessed with a much more pragmatic question: why doesn't anyone on the Internet use apostrophes in their contractions any more? I've gotten used to seeing people totally confuse "your" and "you're" (not to mention "there" and "their"), but come on - "dont" and "Im" aren't even words! (Although I suppose you could partially blame "dont" on the automatic crosswalk signs that flash "WALK" and "DONT WALK" at you - would it really cost the city that much more to buy an appropriately-located apostrophe?)
Maybe I'm just grumpy today, but this article seems to have attracted more than its (note: not "it's") share of failed communicators. The parent post is a particularly egregious example. I remember when even trolls could communicate better than this!
I know, I know: flamebait. Still true, though.
Your right to not believe: Americans United for Separation of Church and
OK, how exactly was that flamebait? Overrated, perhaps, but there was certainly no incitement to a flamewar. What color is the sky in your world, O Moderator? C'mon, meta-moderation!
Your right to not believe: Americans United for Separation of Church and
You're right; consider me suitably chastened. I guess I am grumpy today...
Your right to not believe: Americans United for Separation of Church and
nitpick:
Not exactly - your cells must die for you to remain healthy. Dead cells aren't very healthy themselves :)
Your right to not believe: Americans United for Separation of Church and
Just because it happend on the show Lexx on Sci-fi doesn't mean that is how it WILL happen.
Nice way to put that story in though. Almost word for word the story of the brunungee (killed the spelling there sorry) on the show.
Paying taxes to buy civilization is like paying a hooker to buy love.
The problem with dying of old age is that it is "only" natural. Just because something is compatable with your genes' interests, doesn't mean it's compatable with your interests.
You can worship nature or the gods, and marry and reproduce and care for your offspring and then die to make room for your genes' newer hosts. Let the pre-ordained program have its way.
Or you can have a ambition and a real ego, and declare that your mind is what matters and your personal agenda is more important than the biological program. When you take that approach, attempting to defy nature and conquer mortality may make a lot of sense.
Such attempts may be futile, and trying to apply engineering principles to a complex system that is the product of long-term evolution, is difficult and can run into a lot of pitfalls (ask anyone who has maintained ancient legacy code ;-) but it's heroic to try anyway.
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As copyright owner of this comment, I authorize everyone to defeat any technological measure which limits access to it.
I feel that you should have the right to decline the offer.
I feel that you should have the right to attempt to accept the offer. But success is not guaranteed. (OTOH, you may instead choose the first option, where success will be guaranteed.)
Caution: Now approaching the (technological) singularity.
I think we've pushed this "anyone can grow up to be president" thing too far.
Interesting, when you compare that fact to what's written in the biblical text, book of Genesis; before the flood of Noah, people routinely lived for 600-900 years or so.
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At least mafia-owned pizzarias make excellent pizza. Compare to Bill Gates.
How can we be sure that this isn't just the beginning of the marketing scheme to promote the next big Schwarzenegger bio-warfare shoot-'em-up blockbuster, "The Executioner"?
I bet next week it'll be on CNN, and then it'll start to run amok and kill people randomly, and then there'll be talk of bioterrorism of a kind never before heard, controlled by something that can't be human...
Hey, in this day and age, even Nature magazine can be called into question. (Don't you think they would accept it if Columbia or Universal or whoever offered them a ridiculously large amount of money to run with this?)
Just my two paranoid cents.
To the editors: your English is as bad as your Perl. Please go back to grade school.
So I think that living forever is something that we shouldn't want, and shouldn't work towards.
Gee, thanks for telling the rest of the species what it shouldn't do and think. Just don't find it weird when all the biologists utterly ignore your orders and go on developing this technology as far as possible like they have always done, regardless of whether anyone (especially Slashdot posters) thinks they shouldn't.
-- Kaufmann
To the editors: your English is as bad as your Perl. Please go back to grade school.
Whenever I post something that's intended to be funny, either it gets moderated "Insightful" or "Redundant". Either way, because of it, everyone else takes it seriously too and posts serious replies to it, leaving me in a position to say nothing but "uh, y'know, I don't actually mean it".
Stupid. No wonder I don't spend much time at Slashdot anymore.
To the editors: your English is as bad as your Perl. Please go back to grade school.
Actually, nearly all virii kill the host cell. They 'reproduce' inside the cell, the cell eventually dies, and the newly created virus particles leave the host.
First a correction: cancer and alzheimer are _not_ modern diseases. They have been around for ages. AFAIK
And yes: I believe people really DO want to live forever. Just look at the worlds religions. They all result in eternity. If it's not for the body, than it is for the soul.
Also our western science is hopelessly trying to find the key to eternal life. That's what the research for this gene is all about: trying to let humans life forever.
You are probably right when an avarage guy at this moment discovers that he's immortal: he would get bored eventually, or get very paranoid.
However, I do think that when the human mind is provided with enough chalanges he can live forever without getting bored. And look at the universe: there is enough to be discoverd.
So, in my opinion people should NOT stop believing in God or science (or whatever it is that provides them with the hope of eternity), because this hope is what drives the human mind to discover new things (which is something unique among the creatures that live on this planet).
So I think
:)
You see? He said I think. He didn't think for you
Oh, great. Now we'll have programmers who get laid off at 45 and have to collect unemployment for 75 years because everyone just hires the new kids.
You never really know how close to the edge you can go until you fall off.
Dude, I think blunt trauma would do the job, don't you? I mean, it's a MOUSE...I stun 'em and feed 'em to my snakes all the time.
Why yes, I AM a rocket scientist!
I think you forgot one vital point in your train of thought.
... all it does is halt 'aging' effects.
... after a long long life of coding :)
The gene modification would stop dying from old age, but it doesnt make one imortal.
It doesnt prevent car crashes, cancer, toxic poisoning, etc
So while life might be greatly extended, it wont be imortality, and the question of life or death will be as real as before. If nothing more, it will become more of an uncertainty, will you die at the age of five, or at the age of five hundred
?
Next to all that, i also think the human brain has a limited capacity of adjusting, and remebering.. What happens after 4000 years of adjusting and remebering? I think people will choose their own end. I know i prolly would
-- Chris Chabot
"I dont suffer from insanity, i enjoy every minute of it!"
This is not the fountain of youth. Your cells must die to remain healthy. The fountain of youth would be increasing the number of generations your cells can go through before they run out of steam. That's the fountain of youth problem - replacing dead cells indefinitely, not preventing the death of the cells you have now.
Several signal transduction components are highly conserved in evolution. You may find the same components in amoebas, shrimps and man.
Most the proteins involved in the regulation of cell cycle fall into this category. Any dysfunction of these proteins can result in anything from cell death (cell cycle arest, apoptosis) to uncontrolled cellular division (cancer).
Apparently this is Just One More Piece to fit in the puzzle.
The complexity of signalling pathways is such that simply perturbing one component can have completely unexpected results, in the short- medium- and long-term.
To begin with, there are many different types of cancer. What makes it cancer is that cells that are 'cancerous' do not kill themselves at the proper time, and always undergo mitosis no matter the circumstances. That may be inappropriate if a cell is already surrounded by other cells, for example. Anyway, somehow either the ability to not split or the ability to apoptose (kill self) if beyond repair is removed.
There is a protein called p53 that's responsible for (among other things) detecting damage in a cell, and then either trying to fix the cell, or kill it (apoptosis). The levels of this protein are elevated when cells are in distress -- for example from ultraviolet radiation, starvation, etc. Levels are also affected by mitosis phase, etc etc. In any case, if it is possible to design something that detects high levels of p53 in a cell, and then nondeterministically triggers massive expression of the apoptosis gene (this thing they discovered) then this method could be used to treat some cancers, because in some cancers, levels of p53 are elevated. While this method will likely kill a lot of cells in the middle of mitosis, in a healthy tissue only a small fraction are dividing at any one time.
In some cancers, the p53 gene is damaged and does not get expressed, so in that case some other metric would have to be used to trigger apoptosis.
Anyway, between approaches like this, chemo, surgical removal, and whatever else there is, cancer is slowly becoming a survivable disease.
-S
Apoptosis is, as the article hints, a vital part of development - at various stages of embryogenesis, tissue that has developed needs to be removed for the next step. Apoptosis is also involved in the regulation of cell growth. If a cell detects that it's becoming non-functional, apoptosis is triggered and the cell dies. This is absolutely vital in cancer prevention. Every day cells in your body pick up chance mutations that could potentially lead to cancer, but in the vast majority of cases they kill themselves before this can happen. However, if a mutation occurs in the pathway that triggers apoptosis then this can't happen, and the cell may go on to become cancerous.
AIF is important because it's likely that many cancers will have a defective copy of it. With advances in gene therapy, it should soon be possible to insert new copies of the gene into the cancerous cells thereby triggering apoptosis in them and destroyin the tumour. However, it's not much use for making you live forever. You don't die because cells decide that you've lived for too long - you die due to disease or failure of organs induced by wear and tear and picking up of mutations. It's possible that inhibiting AIF might lead to some individuals living slightly longer, but only because cells that are defective would hang around until they broke down completely rather than killing themselves cleanly. It wouldn't be terribly pleasant.
(Note: IAAB)
it seems to me that you are suffering frim LIMITED SUPPLY PHILOSOPHY that there should be limits. that there is a limit to how safe one can be.
risk is part of life. the struggle of life would not disapeer. only change. if you lived forever would you exept the artificial and arbitrary standards we now life under?
IMHO people would change to be something better. why? because scare tacties based on dealth and restriction become useless, with unlimited supply.
we are already seeing this with the unlimited supply of the information on the internet.
do you really think that the massess would work as they do now? eternal hard boring work is the classic defintion of HELL. no, the masses would DEMAD changes. they would see how us hackers play / with our work and DEMAD the same. not that they would become hackers, but do that which they enjoy at the monent and like doing.
IMHO those that can't accept unlimited life. will do themselfs in, or change. with limitless time, this is really no reason to have petty greed, (what would you be greedly for?) or fear. if do didnt do it right today there is a limitless supply of tomarrows...
nmarshall
The law is that which it boldly asserted and plausibly maintained..
nmarshall
The law is that which it boldly asserted and plausibly maintained..
--Colonel Burr 1783
I would also venture to say that the CPU isn't like the CPU in our computers which are imutable, but change as the cells specialize. The "Stem Cells" are virgin cells which haven't specialized yet, thus the same DNA strands would produce different results in different cells after they specialize.
We know that DNA is very vulerable to coruption from all kinds of bad things like radiation, carcinigans, lab research on rats. I think the best comparison might be memory leaks, inadquate bounds checking, or pointer errors in our world.
The cell self-destruction might be safe guard against bigger problems. Kind of like a like rebooting your system every so often.
Cheers
This is a boring sig
If it can kill cells, it could make a damn hefty genetic virus (okay, maybe that's a cartoonish thought. but still.... *shiver)
To get Vonnegut's take on the this issue, read "2BR02B" in his new book Bogambo Snuff Box. Actually, this is Vonnegut's take on the issue from before I was born. Bogambo Snuff Box is a collection of short stories by Vonnegut that were published in magazines early on in his career.
Frogs are primitive animals - so the occasional extra toe is not that unusual. But this is very unusual.
I cen see not wanting to live forever, but what about an extra hundred years or so? Many people are just getting really good at their jobs in their 40's. They only have 20 more years left to work then retire and die. Could you imagine a network engineer or a programmer with 100 years of work experience?
Ok, for starters: I really recommend that anyone interested in this stuff pick up a (modern) book on biology and genetics, there's a lot of stuff been discovered in the past 10 years, and we're only just scratching the surface. (Someone will make a lot of money selling computers to process all that info :).
This gene has been predicted (if not known about) for some time. It's needed, because your cells die all the time, they're supposed to. Over time, you get problems - errors - in DNA, and this is one of the problems with making cells that duplicate forever, eventually, they won't do the same things anymore (IIRC, brewing companies need to change the yeast they use periodically, because mutations that occur over time change the taste of the beer). The cells in yeast aren't all that different from the cells in your own body! (Actually, anyone who has problems with evoloution would be shocked at how much your cellular processes are (identical) to any other furry mammal).
The biggest application of this kind of technology is the real limit on human lifespan - brain cells. We can eventually replace almost everything else, somehow, but your brain is what and who you are. Once it deteriorates, you're not the same person anymore. Figuring out how to prevent brain cells from dying - brain cells are unique, in that they do not reproduce, ever - just the supporting (gidal?) cells do.
Nobody will be living forever until nanotech becomes rampant - no other mechanism to repair nerve and cellular damage is possible (and even then, it might not be enough). I wouldn't mind retaining my mental facilities until I reach the end of my lifespan, though. If you figure you'll probably live to 80, but will be signifigantly handicapped after 60 or 65, that's a 15 year productive increase.
..don't panic
Maybe I missing the plot, but who wants to live forever.
I think more emphasis should be placed on the quality of life, not on the quantity.
Most of these measure we take to preserve life just mean a few more years in the retirement home.... again am I missing the plot???
When you think about it, you are dead for so long, that in the grander scheme of things, a couple of years will not make a difference.
Also, most of us cannot find stuff to keep us entertained when we are on holiday, yet we want to live forever.
Here's to la dolce vita.... the sweet life, or as the Chinese would say, may you live in interesting times.
Live today. Tomorrow will cost a lot more!
I think you missed the point. AIF *saves* cells, it doesn't kill them. That is why it is possibly being regarded as a 'fountain of youth' drug.
If it is applied to cells that a virus would attack, then the cells will not die, so the virus will be unable to reproduce, and therefore will die out.
More remarkable than the stories in this collection, is its title :) I have only read the first, maybe I should go and read the rest.
A truly, truly superb story , set in the fifth millennium and based around a man born in 1912, is "Time Enough for Love", by Robert A. Heinlein. This may be one of the greatest works of fiction ever written.
Why do you think we'd all get scared and hide? We don't do that now, and we have a much better (worse?) chance of irrevocably dying than any future generation does. How many people smoke cigarettes, fully knowing that it shortens their life? You think people would hide in their houses if they were offered a chance to live as long as they wanted?
No, I seriously doubt it. In fact, I take the opposite view. People would became incredible risk-takers. If you've lived 300 years, you'd probably become pretty bored and start jumping out of airplanes (or space shuttles or whatever), because you just didn't care any more.
It's really basic psych.
What I meant by 'irrevocably" was that future generations may very well have the technology to resurrect themselves. It's not really that far-fetched, if you consider that we can already bring people back from brain death today, as long as they are lucky.
I thought that was St. Francis of Asisi that said that....
Maybe you'll return to Minagua, You could go unnoticed in such a place. -FZ
The reason you age is because the cells are unable to perform perfect dna copys when duplicating. The resulting dna is shorter and progressively more damaged.
That is why you age, and when the damage accumulated is too much, you die.
If a the cells can be made to perform perfect dna duplication always, then you would not age.
And if the dna sequence are more redudent and self-repairing, (or some other way so that damgage will not accumulate) you will have a indefinite life span.
Go into biological research if you wish to live long.
But the ability to live forever would really give us the ability to choose when we die. Maybe people wouldn't want to live forever, but I personally would love to live several times the current average human life span, then get my affairs in order before ending my life in a manner of my own choosing.
In addition to the cell reproduction (you'd need to find a way to either preserve or repair telomeres, which IIRC wear away during cell division), you'd also need to find a way to repair DNA strands damaged by UV and other agents (or, more drastically, kill and replace damaged cells).
Only the dead have seen the end of war.
Er... Boss? How do we kill them?
I'm trying to teach myself to set people on fire with my mind... Is it hot in here?
Did you actually read the posting? The poster said 'I think'. They werent making any grand pronouncements for everyone.
My blog: http://jkratz.dyndns.org/~jason/blog/
So he's a dumbass due to scale? I happen to agree with him; I want every medical advance possible to prolong my life as much as possible. I happen to enjoy life, and I can't even remotely fathom having time enough to do and experience everything that there is to do now within the next 1,000 years, nevertheless all of the cool shit yet to come. I think about all of the amazing stuff that has happened over the past couple thousand years and feel only sorrow that I won't get to live through the next few thousand. I certainly wouldn't demand that a long lifespan should be forced upon everyone, but I would ask that others not dictate my lifespan as well.
Deosyne
The stimuli that invoke apoptosis are usually factors that will kill the cell anyway--starvation, poisoning, radiation damage. Apoptosis is the cellular equivalent of euthanasia. Without it, the cell will still die anyway, except more slowly, and it will rupture and spew its contents to surrounding cells, possibly causing those cells to die as well. The process of aging and death of a multicellular organism is ultimately mediated by entropy, not genetics, so until we can figure out a way to repair the ultrastructure of a cell with nanotechnology, immortality is still a long way away.
What this discovery does allow us to do, however, is stop apoptosis in very specific situations (assuming that we have figured out all the cascade mechanisms, which is probably not likely at this stage). For example, in the aftermath of a heart attack, a stroke, or hypotensive shock, even if blood supply is restored, cells will still commit suicide because the apoptotic pathways have been activated. Experimentally, it has been shown that if you can block the stimuli that initiate apoptosis (such as the excess glutamate released in a stroke), then in these specific situations, the cells will probably do fine once the blood supply is restored.
So there are ways to shut off genes transiently--antisense RNA, competitive inhibitors of transcription factors, etc.--preventing much of the sequelae of these vascular events.
Still, shutting off apoptosis, even transiently, has the risk of inducing cancer. In stroke, for example, the excess glutamate triggers a cascade that generates factors that damage DNA. (These DNA-damaging factors are what directly activate the apoptotic pathways.)
So it's a choice: would you rather be paralyzed, or would you rather have a tumor? The odds are probably not even, so there would be a better choice, but ultimately, entropy can't be stopped, so achieving immortality would probably entail a lot of micromanagement.
Of course muscles regenerate. When you work out you're tearing tissue all the time. That's part of the reason you're sore afterwards. Bulking up has to do with muscle regeneration and repair.
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"People who bite the hand that feeds them usually lick the boot that kicks them"
Higher Logics: where programming meets science.
Actually, it is absolutely impossible to live forever. One day you WILL die. Maybe not from old age, but the longer you live the more likely you are to die from an accident. And if you manage to escape all of those, there's still the death of the universe to deal with, so there's no winning in the end. So if you think about it, there are two choices: a) grow old and die a peaceful death, or b) try to live as long as possible and eventually die a horrible violent death. How's that for sunny news? :-)
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"People who bite the hand that feeds them usually lick the boot that kicks them"
Higher Logics: where programming meets science.
But alot of the stuff you're talking about has more to do with lack of maintenance more than old age. And yes, I have visited alot of nursing homes so I know exactly what you mean. The truth is, people just don't know how to take care of themselves, or they just don't bother. I read an interesting article once about a man(a cop incidentally). The guy was incredibly muscular and unbelievably cut; he would almost put Arnold to shame. Do you know how old he was? Over 60. Over 60!!! There are people over 70 still running marathons, there are people who are over 100 years old still actively working on farms. They're all still fully functional, completely able, and still sharp and fully aware of themselves.
I know for a fact that I will never become someone trapped in a nursing home because I will never let it happen. Granted, there are unavoidable cirumstances that force people into that kind of care. Alzhiemers, dementia from repeated heart attacks, strokes or aneurysms, physical problems such as paralysis from accidents and such. But I honestly believe that alot of people that end up apparently debilitated and unable to care for themselves, are themselves the problem(note, I didn't say everybody). I am of that belief because I see it everyday in my family. In my opinion, all it takes is will power, and if you don't have enough to get up and keep yourself in shape, then it's your own fault.
Chalk me up as uncaring, cold-hearted, I don't care. I know what I've seen.
On a more philosophical note, age and it's associated change of life patterns can be good for people. It can change attitudes and it's especially good at shattering the younger generation's notions of invulnerability (disclaimer: I still suffer from the dementia myself) As one of my favorite mentors once said: About death and watching people die, well guess what? That's life isn't it. Life, death and rebirth. Every day you should be aware of the fact that either you or someone you know can die at any moment. If you can't live with the thought of losing someone, then maybe you should end your life now. That is the only way out because otherwise you will have to live with the experience of losing someone you care about. As a closing thought(god, I sound like Jerry Springer):
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"People who bite the hand that feeds them usually lick the boot that kicks them"
Higher Logics: where programming meets science.
As for having the will-power to keep yourself in shape and thus countering the effects of aging, that's just a delaying action at best. You will still die. That "ripped" cop will look good at his funeral. Those 70-80 year olds who run marathons will be running until they have a heart attack and die. In the end, all physical fitness does is delay the inevitable.
;-) I'm just saying that we should never walk into anything blindly.
That's right. It is inevitable. I wasn't disputing that. I was arguing that growing old and dying doesn't mean slowly withering away and becoming more debilitated and dying like you said in your previous post.
Science can help to delay the inevitable even further.
I'm sure it could. No disputing that. I was just trying to shatter the common conception that getting old means becoming frail, helpless and in need of constant care.
Not to mention the fact that as you get older, you increase the odds of some limiting disease or injury that will reduce your ability to work out.
That's true. But I bet that the people who let themselves become frail as they age are the ones who have the most difficulty recovering.
By the way, some extremely unhealthy people live to be very old, and some really healthy people die in their 50's. Excersize is no guarantee.
Very true. In probability and statistics, those cases fall into called the Standard Deviation category. The mean is what's important when looking at general trends. The general trend suggests that taking care of yourself can lessen many if not most of the problems associated with old age. The mean is what most people will experience if they take care of themselves.
Oh, and thanks for counseling suicide for those who get upset when friends and family die.
Well, sometimes outright bluntness and shock are the only ways to get through to people. I wasn't counseling anything, I was merely stating a fact. Logically speaking, the only way to escape not having to endure such loss is to end your life before you encounter such a situation. There is no other way. Any continuation of your life must be accompanied by the realization that you will lose people you care about. I don't support suicide, I would never contemplate it and I have smacked friends who have tried and/or even considered it.
I wasn't saying that the death of a loved one was an event that couldn't be survived, I was saying that there is no event that will more wrench at your soul.
And I didn't dispute that. I know you didn't mean that such an event wasn't survivable; I've survived it, and I'm sure you have. But the reality of life never leaves my mind. People will die, sometimes for good reason, sometimes for no apparent reason at all, but it will happen. Unfortunately, it seems most people just ignore the thought of death as if it could never happen to them... then it comes crashing into their lives and they have no defense against it.
But it would be nice to remove the element of certainty from death. The knowledge that you WILL die, and you have just moved one day closer to that death.
Nothing will ever do that. You will die whether you find the elixir to immortality or not. Eventually, you will have an accident and die or you will be killed at the end of the universe. That's as good as forever for most people, but the day will come. Just because you've gotten rid of old age does not mean death will disappear. As you said yourself, the longer you live, the greater your chance of having a fatal accident. No matter how hard you try, there is no escaping it.
It would be nice to think that, hey, maybe my friends and I will still be hanging out together 50 years from now. Or that I will still see my mom every year for the holiday season up through the next century.
If you thought deaths were depressing and hard to deal with before, wait till everyone becomes 'immortal' and someone dies in an accident. If people naively ignore death now when it is a part of their everyday lives, think how much more shaken they will be when someone they care about dies. They thought they had gotten rid of death and it comes crashing back into their lives.
A death will become a hundred times more tragic and painful when you realize that this person could have lived another 3000 years and now it's over. When you thought you had eternity to get to know them, to be with them, then you blink and they're gone. People already have little defense against this; add immortality to the equation and I can only see it getting worse.
You may think immortality is a blessing, but perhaps you should think deeply about the consequences. I'm not saying we shouldn't pursue it, that I wouldn't want to have the choice. I would certainly love the chance to live another 100 years(or 2
A time limit on a person's life should make him think alot more about what's important, what he wants to do or accomplish while he has the chance. Is it really worth going to work those extra few hours when you could spend it with your son/friends/girlfriend? Is work really that important? If you were immortal, would you ever get the feeling that you were wasting your life away doing something? Would you ever get the thought 'why am I doing this? I'm wasting my time and my talent, I'm capable of so much more'? Would you ever get the urge to actually do anything with your life if you could keep saying to yourself 'I have at least another 10,000 years, so what's ten years doing this meaningless crap'? Do you really feel that's a good thing? Subsituting quality for quantity has never worked in any situation I have ever encountered. Why would it here? Why would it make life any better?
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"People who bite the hand that feeds them usually lick the boot that kicks them"
Higher Logics: where programming meets science.
You are probably thinking of telomeres, which are foundon the end of genes and gradually disappear as the cell generations increase. When the telomeres are gone, the cell won't reproduce. This doesn't mean that the cell itself will die.
Apostasis is an internal or external signal for the cell to self-destruct. People with webbed feet or hands are the result of insufficient apostasis in fetal development...although this is merely a small example of its importance.
Well, it's a possible way to keep killing all the cells harbouring nasties before they spread, and of killing of malignant tumours. If nothing else kills you, cancer will - it's basically cells malfunctioning, so it's a product of age. If you can control a great extent of illnesses with it, which you could if the targeting was perfected, you've got the cure to all disease.
All you've gotta do then is convince all the good cells to keep reproducing. Though the AIF probably controls the Hayflick number, so you can probably beat that too.
Sounds alot like a recipe for immortality to me.
toeslikefingers.com - because
Well, it's been a few years since I left the lab, so forgive me if I'm wrong, but isn't there already machinery in place which at development and later extends the telomeres with C repeats?
I can see me smearing on a gel of that sort of stuff and having a big milkshake every week..
But now we're getting silly. You're right, there's alot of barriers. The interesting thing with cloning is that we're realising some things we thought were important, like the telomere issue, aren't quite so important. And some issues maybe are. Bloated fat mice, anyone?
toeslikefingers.com - because
You're only half wrong. You can't kill the cells directly. But if you can quickly kill the cells which are harbouring the virus quickly, then you can stop it reproducing.
Cells have this clever way of grabbing parts of the viral capsids you've described and displaying them on the cell membrane, their surface. So what you do is program a virus with your AIF, then culture that virus within your patient's cells. if it's the right kind of virus (bear with me here, I'm skipping two years of college biology to explain this quickly) you get a virus which is encapsulated in your own cell membrane, and will be accepted by other cells.
Now, in a method as-yet not determined, you get the virus to target cells with the viral fragments on the surface. The custom made virus then infects these cells, and quickly exterminates them, thus your virus won't keep spreading.
Please bear in mind that this is really science fiction - but there are biological entities which perform all of the above. Give protein function and viral vectors fifty years and I would expect this to be a valid reality.
toeslikefingers.com - because
While this is a valid point for Americans who can't write correctly in their own language, please keep in mind that there are plenty of non-american slashdot readers, like myself, and English is not our primary language. I usually do my best to avoid grammar and spelling disasters, but hey, give me a break, not everyone Speaks English all day.
"Luck is my middle name," said Rincewind, indistinctly. "Mind you, my first name is Bad." -- Terry Pratchett
Humans just aren't ready to accept eternal life in this world.
Aside from the things that you mention, I think many humans would also not want to live forever because it would mean never seeing God. I think that is the best reason to "want" to die. The things you can do with infinite time in this world can't compare with the wonder and glory of God in the next.
Go ahead, mod me down since I mentioned God.
THIS SPACE FOR RENT
My outlook is that immortality would be boring. After a while everything there is to be done you've already done so you get cynical and go around trying to insult everyone in alphabetical order just for something to do.
----
ADVENTURERS! - ANTIHERO FOR HIRE - CARDMASTER CONFLICT
"Hope I die before I get old" - The Who, song
"I hope I'm not still rocking on when I'm middle aged, that would be sad" (paraphrased)- Elton John, Parkinson interview
The moral: The you 20, 40, 400 years down the line is a different person to you now. Don't go making decisions for them now.
Rich
--Fesh
--Fesh
Kill -9 'em all, let root@localhost sort 'em out.
So is this new? Perhaps it is the discovery of the gene that is new, but nto the knowledge that cells can commit suicide.
Good point. 'I' am not the sum of my parts -- confusing mere cell-life with organism life is a mistake. I don't care what happens to my individual cells, as long as 'I' as an organism continue.
The next question is: is there 'me' beyond my biology. I should hope so.
-- @rjamestaylor on Ello
So what makes a humanbeing these days? A species who doesn't have the time to live. First 20-25 years used to take a high paced race through childhood, youth, education. Preparing them for the "real" life.
... to live!
Next 25-30 years spend at being a good taxpayer. Work, mortgage, carloan first. Prozac, painkillers, therapy and other stress/poor childhood induced diseases second. Life and family last... if there is resources left for that.
If they are lucky enough to survive "life" they are ready for retirement. The time to live. But to late. You are old, grumpy, your kids hate your. But you don't care, alzheimer have killed all memory of them.
I don't see why eternal youth should be so awful. You get time to grow up. You get time to take an education. You get time to be a parent. You get time to love. You get time to do your hobbies. You get time
Could be an off switch for our creator(s).
The little hood or the sickle it carried?
DanH
Cav Pilot's Reference Page
Cav Pilot's Reference Page
UNIX - Not just for Vestal Virgins anymore
If I recall, the gene is activated whenever the cell's DNA structure tends to get too old, measured with respect to the tail of the chromosomes.
Anyone got any idea whether this is the same thing?
<()>
Not really YOUR 2 cents eh :)
:)
Oh well I guess the effort should count
"On a long enough time scale, everyone's life expectancy drops to zero."
All we'd need to do is stretch this time scale a little (ok maybe a lot).
Here is a link to one man's list of criteria of what makes something "alive." He admits that there is some disagreement among scientists about what "life" is. From his list, virii: (1) don't have cellular organization, and (2) don't grow or have a motabolism but they can (3) spread their genetic information to offspring.
Since it does not possess two of his three required traits, virii aren't alive.
Yea,starting with the White House and Congress.Any way to activate it remotely? ;]
Geek Hillbilly
If you didn't, would you have posted as Anonymous Coward?
With immortality would, of course, come responsibility. It would probably mean that the idea of a free society where wastefulness and pollution is tolerated would have to be abandoned.
The nearest example I can think of is the China model. If you live in a city and have more than one child, you'll get economically punished by the state.
Did you read the article? Without the gene programmed cell death cannot occur and growth cannot proceed beyond the embronic stage.
Programmed cell death is required for all types of cells for normal operation of the body.
Blasphemy! Here in the US we all have an obligation to live as long as possible, regardless of if we have any mental capacity left or not. You many not, under any circumstances, want to end your life, and we have machines that will keep you alive indefinately. Anyone who disagrees must be mentally disturbed and can be sent to thearpy and kept alive until corrected.
Man, i was just considering that last night... I found this quote: 'Animals first learn death at the moment of death. Man approaches death with the knowledge it is closer every hour and this creates a feeling of uncertainty over his life, even for him who forgets in the business of life that annihilation is awaiting him. It is for this reason chiefly that we have philosophy and religion.' - Arthur Schopenhauer. Pretty true IMHO... but yes - i mean, whats the worst thing that can happen in life... i don't really think it's dying :)
Live like you don't have a tomorrow :)
"... this part of what makes us human."
Baloney. Fear of death does not "make us human." Other animals also fear death, to the extent they understand it, and some do. "Fear of death" is a normal evolutionary development to any species, not just humans, since such a fear naturally has survival benefits. If anything, it is consciousness that makes us human, and that's turning out not to be such a fancy trick as once thought.
"... soon the wonder would fade ..."
Science and mathematics show no sign of slowing down and running out of wonders. Nor does the production of entertainment. There will be new experiences to have and new thoughts to think for thousands of years, at least.
"... fear would set in ..."
A few individuals might develop pathologies, but most people would not. Already, most people have a poor grasp on things more than a few years in the future. The value they place on future benefits compared to present benefits (as shown in saving money versus spending, eating poorly versus maintaining health, et cetera) shows they do not highly value future benefits. Would the prospect of an infinite future change this? Not really. If a benefit a year from now is worth only 90% of the same benefit today, then the sum of an infinite stream of benefits is worth only ten times the value of the benefit today. An infinite future has a finite value, and hence is only worth a finite amount of effort to protect.
In other words, emotionally people are willing to trade off future benefits for current benefits, and rationally that is the right choice for an appropriate return rate. It would not be reasonable to forego all of today's benefits in exchange for an infinite lifetime if the infinite lifetime contained no benefits. Nor would it be reasonable to take great risks today since they would jeopardize an infinite lifetime of some benefits. Emotionally and logically, the optimal course would be some intermediate path, taking reasonable risks for reasonable pleasures.
Yeah, living forever probably wouldn't be too fun, I'm sure it would get tiresome and trival pretty quickly. But maybe an extra fifty or one hundred years would be a treat! But if you think about the way it would happen it could be less enticing. For example, if one could live 200 years say, instead of the say, 75 of average life expectancy now, would it happen that all the periods of life are uniformly extended? That would mean longer adolecence and longer time being elderly and frail. Or if this, life-giving-serum were applied during life, maybe it would just extend life through the elderly period, so you would get to 80, 100 etc, but just be increasingly frail and beset with problems until you stop taking the serum. I don't think anyone would want *that* sort of eternal life. The type most people would be interested in would be an extended middle period, or really lower middle, late 20's to early 30's, and to have this physical condition extended, or the deteriation slowed down perhaps. This would also benefit society in general, as people would be unable to work for less of their life, and the proportion of people in the workforce would rise. Of course I realise this is all bullshit conjecture of the most uninformed nature, I'm just board.
// It had been Fat's delusion for years that he could help people. --Philip K. Dick, Valis
Look on the bright side - we'll probably all be dead before this becomes even remotely practical, if it ever does.
Think about it, you can't just remove the gene. Cells NEED to die to make way for the new ones which are created, if they did not we'd invariably become lumps of suffocating flesh.
So, we'd need to selectively remove the gene... I have no idea how this would be done, or if it would work.
As for losing the fear of death, there is one major failure to your argument: we could still die if this gene was removed. Having cells not die wouldn't protect you from a fatal wound, just from death by old age.
And IF we instituted the no-death policy, think about the boom in population! You'd have to curb it somehow - forced sterilization of those who have the gene removed comes to mind. Perhaps a combination of that and only offering it to those who do not have offspring? Needless to say, this wouldn't go over well with the American Way. (Large family, Large house, Large paycheck).
-Medgur
I think it has more to do with reduced blood flow starving the cells of oxygen.
This is exactly what I was thinking when reading the article. I was always taught that heart cells died in a heart attack due to lack of oxygen. That's why the article was very confusing on that point.
Can anyone with medical knowledge give us any insight? Perhaps oxygen-starved heart cells start a chain reaction to other cells in the area that are still oxygenated? Just a wild guess. A medical researcher must have had a good reason to make such a statement, but its true meaning is not clear. Can anyone clarify?
"Love heals scars love left." -- Henry Rollins
"Spread Christianity wherever you go, and when necessary, use words."
If, on the other hand, your purpose was to troll, then I advise you to go stick your head in a running blender. I'm sure you can make it fit.
Bugrit! Millenium hand and shrimp!
So it was, if you meant Assisi. Can't remember where I got my original reference, but a quick Google search proves you correct.
Bugrit! Millenium hand and shrimp!
I don't imagine that living forever is something everyone will do. I imagine that there will be things that kill us off, such as having our internal organs swiftly removed from the protective coating that is our skin. But, sudden-death and accidents aside, I don't think that everyone will want to live forever.
If I had the opportunity to do so; if I knew that I could live indefinately, I might have less ambition. I might take things more slowly, stop from my 9-5 job and "smell the roses" more often. I might live to be over 100 years old. I think I might want to live to be 500 years old, because there are alot of things I have thought would be fun to experience which I estimate would take about 500 years of living to accomplish. But I also think that once I have done everything I want to do, and I've exhausted my capacity to remember, I would want to die.
When I think about dying today I tell myself that I do not want to die because there are things left that I need to do. I need to find a wife, I need to have children, I need to watch these children grow into adults. I need to finish this perl project, I need to recreate this really cool game I played back in the early 90's, I need to accumulate all the things that are required for all my goals. These are the reasons I do not want to die at the moment. In another 300 years I might feel differently, and I'll be ready to leave.
It would be very good to choose when I die.
:)
Your right I wouldn't want to live forever
But I wouldn't want to be dead forever either.....
It's nowhere near that easy!
Think about it - for a virus to spread, the host has to live long enough to spread it. People fret that HIV could mutate so that it killed hosts in six months. But if it did, we'd wipe out AIDS in two years, because we could detect infections and prevent their spread much more effectively.
The same issue is true inside your cells. If that virus injects its genetic material into your cells and immediately kills the cell through apoptosis, then the cell's machinery doesn't have time to manufacture copies of the virus. Such a virus wouldn't even infect you, because it would never get replicated! You'd lose one cell for each copy of the virus that invaded your body - no big deal.
You could try to engineer a virus that copies itself inside your cell, and *then* triggers apoptosis. But this is inefficient, because viruses typically lyse (burst) infected cells once they've replicated many copies anyway. No need to waste time inducing AIF.
To spread successfully, a virus doesn't want to kill it's host. We can successfully contain ebola in isolated outbreaks and we eradicated smallpox. But when was the last time we successfully contained a rhinovirus (common cold)?.
I stole this sig from someone cleverer than me.
It doesnt prevent car crashes, cancer, toxic poisoning, etc ... all it does is halt 'aging' effects.
Hence my post talking about an increased fear of risky activities and so on... that was the whole point of it really.
Jon Erikson, IT guru
Interesting article, and I can only hope that this research pays dividends when it comes to medical research into curing such modern diseases as cancer and Alzheimer's which cause so much misery and grief.
But the idea of living forever... who would really want to live forever?
It's the sort of idea that sounds like a utopian fantasy when you first hear it. After all, nobody but Hamas suicide bombers wants to die - the fear of death is an inherent part of what makes us human. In olden days berserkers were feared for this reason - they would attack and attack without regard for their own safety, and would invariably take many down with them.
But living forever would pervert this part of what makes us human. At first it would seem like a wonderful freedom - all that time to do new things, to experiance more without worrying about not having enough time. But soon the wonder would fade and the fear would set in. Fear of death, fear of any risk which could injure yourself and fear of not being able to afford to live in a reasonable manner.
This fear would overcome any benefit eternal life could bring. People would stay in their houses, attempting to stay safe. They'd stick with their confortable jobs, never taking any risks, never letting their ambition thrive. And when you live forever, enemies are easy to make and friends easy to lose. When there's a lot more to risk, people won't want to risk it.
So I think that living forever is something that we shouldn't want, and shouldn't work towards. Humans just aren't ready to accept eternal life in this world, and we won't be unless we overcome our petty greed and our fears. And Star Trek aside, I just don't see that happening any time soon. There are too many people with too much to lose from disturbing the status quo.
Jon Erikson, IT guru
It deals with the same theme and the sociological implications of an immortal "ruling class" in a gerontocracy?
Yeah, why invent antibiotes and life-prolonging medical techniques because, after all, we all die.
it may be all great that we get our body to live long, but there is more and more evidence that our brains are designed to stagnate over time. you know how the older people are the harder it is for them to learn? or how they become more stubborn? closed-minded?
think of this. evolution has designed an amazing organ. the brain. the brain is superb at learning, especially when it is young. the organism survives if it learns the correct patterns for survival. the older the organism gets, the better it's patterns in the brain must be. so the brain slowly shuts off it's ability to learn over time because it is a winning evolutionary strategy. if it works, don't fix it.
so we may conquer the failing of our flesh, but our minds are a totally different ballgame. imagine what a pain in the ass you'd be at 600...
--
in this age of communication i'm just not getting through
Although find a way to implement this in an already living creature... And... Of course, that's 1000x more difficult, but still...
I was just discussing this with a few colleagues yesterday:
Because tumor cells are already so screwed up genomically (if you do a karyotype + FISH, you don't see nice little arranged pairs of chromosomes, you see a MESS. Inversions, deletions, transpositions in almost every single chromosome. You even get aneuploidy), that is why they are resistant to standard apoptosis pathway applications such as Calcium or Fas-L. However, the interesting thing is, it STILL executes some stages from apoptosis, such as the flipase activation, which inverts the cell membrane. It just happens that lysosome degeneration and subsequent DNA fragmentation do not occur, so the cell is still "on".
The worst thing that happens is the inversion of the cellular membrane. This results in the cell surface markers and sensors to be oriented toward the inside of the cell, and therefore: 1) it is not detectable by immune surveillance, and 2) it shuts down cell-cell communications and thus prevents any more apoptosis signals from reaching their destinations; furthermore the new lack of sensory information is what causes the cell to lose both anchoring capabilities and so-called "contact inhibition" (where the cell will continue to divide even if there isn't enough room).
However, since the paper is talking about mitochondrial relationships to apoptosis, it is also interesting to note that because mitochondria co-exist separately from the host cell nucleus, it is possible to cause mitochondrial apoptosis, and with no energy generation available, the host cell dies along with it.
Enthusiasts of "all-natural" drugs rushed to stores these past few weeks to buy the latest pills, in hopes it would make them happy and healthy looking like the models in the commercials. Though these "Apoptosis Inducing Factor" pills are commonly associated with death, that didn't stop these proud souls, as they bought them by the pallet.
In other news, the average IQ of the world has gone up dramatically in the past few weeks, leaving researchers puzzled.
Kurdt
Kurdt
I'm not anti-social. Just pro-technology.
Now, if only venture capitalists could start throwing as much money on researching this cell as they have spent on e-pets and "get paid to surf the web"-companies, we might have something cool in a few years!
Will code a sig generator for food
There are MANY genes involved in the process of apoptosis. The deactivation or mutation of several of which are required for cancer. A cell that starts dividing like crazy, regardless of DNA damage or cell-cell signals is normally stopped cold and self-destructed via apoptotic genes. When a cell loses that function, it is well on its way to being cancerous.
Longevity is not simply some apoptotic barrier, it is due to many factors, much of which is tied to DNA damage. You DON'T want you damaged-DNA-containing cells to keep reproducing in order to keep you young. The cost of your extended youth would be many abnormal tissues, malignant and non-malignant tumors, etc. Simply stopping apoptosis isn't going to make you forever young, it simply would be accomplishing some of the initial required steps for cancer development.
What you really need is improved/more DNA protective machinery (free radical scavangers) and repair machinery coupled, telomere length maintenance, and STRONG apoptotic mechanisms to catch the damaged cells that get past the repair machinery. THEN you get longevity without the abnormal growth of cells that shouldn't be permitted to continue.
In Bushworld, they struggle to keep church and state separate in Iraq as they increasingly merge the two in America.
Although I salute your obvious knowledge and respect for the bible, do these quotes really have anything to do with us genetically altering ourselves so we don't age?
Obviously, the lack of aging wouldn't make us immortal, there are plenty of ways to die, age being one of them.
I think the only thing that bugs us about this (age) is that until now, or at least the near future, we had absolutely no control over it. It was inevitable, if something else didnt kill us first, age would eventually. I think this is why it was so focused upon in many religious writings.
However, in our world today religion is taking a backseat to science. Perhaps in the past a scientist who saw such an amazing opportunity as stopping the aging process may have quit his research in fear of God's wrath, but I assure you if there is even a chance that this could be done today, it will be.
---The problem with being better than everyone is that most people tend to think your pretencious.
Still, aren't there some types of cells in the body that don't regenerate? I can't remember offhand, but maybe it's cells in the brain or elsewhere in the nervous system that don't regenerate. Any biologists want to answer this?
Dang I thought this article would relate to http://www.cellphonebashing.com not some genetics debate!
Are you lonely? Hate having to make decisons? Meetings, the practical alternitive to work.
So if they find a way to turn it off... and cells stop dying.. damn it, haven't they seen Akira? When cells reproduce uncontrollably without dying IT AIN'T PRETTY!
End of lesson. You may press the button.
The REAL jabber has the /. user id: 13196
The REAL jabber has the user id: 13196
What you do today will cost you a day of your life
Of course! Don't kill the virus directly, but the cell that hosts it, so that the virus can't reproduce!
Thanks for the detailed explanation.
I code, therefore I am.
Being able to kill off cancer cells and other types of viruses(maybe) this could have huge value to people.
IANAB, but I as far as I know, viruses are not cells. From this article on viruses structure, here are the components of a virus:
The bottom line is: this cell killer gene will not help fighting the flu.
--I code, therefore I am.
Basically there are two ways:
1. Insert new DNA into the genome that codes for the gene you want. This gene is used as normal by the cell. Mostly this is achieved by infecting the cells with a specially constructed virus.
2. Inject genetically transformed stem cells, which gradually replace or supplement your current cells.
But in reality our practical knowledge of such method are in their infancy and such gene therapy techniques are still a few years off yet.
My very wrong what?
-- If no truths are spoken then no lies can hide --
The Doctor of Death Island by Gene Wolfe.
Short story describing a near future where humanity has defeated the age problem.
-- If no truths are spoken then no lies can hide --
Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death
NICHOLAS JOZA, SANTOS A. SUSIN, ERIC DAUGAS, WILLIAM L. STANFORD, SARAH K. CHO, CAROL Y. J. LI, TAKEHIKO SASAKI, ANDREW J. ELIA, H.-Y. MARY CHENG, LUIGI RAVAGNAN, KARINE F. FERRI, NAOUFAL ZAMZAMI, ANDREW WAKEHAM, RAZQALLAH HAKEM, HIROKI YOSHIDA, YOUNG-YUN KONG, TAK W. MAK, JUAN CARLOS ZÚÑIGA-PFLÜCKER, GUIDO KROEMER & JOSEF M. PENNINGER
Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis and tissue homeostasis. In mammals, release of mitochondrial cytochrome c leads to the cytosolic assembly of the apoptosome-a caspase activation complex involving Apaf1 and caspase-9 that induces hallmarks of apoptosis. There are, however, mitochondrially regulated cell death pathways that are independent of Apaf1/caspase-9. We have previously cloned a molecule associated with programmed cell death called apoptosis-inducing factor (AIF). Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli. Here we show that genetic inactivation of AIF renders embryonic stem cells resistant to cell death after serum deprivation. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies-the very first wave of cell death indispensable for mouse morphogenesis. AIF-dependent cell death displays structural features of apoptosis, and can be genetically uncoupled from Apaf1 and caspase-9 expression. Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis.
My .02,
My .02,
zencode
iactivist.org/jason
"...it could potentially open the discovery of a true fountain of youth."
OR...it could potentially be turned into the most potent bio-weapon in the history of mankind, destroying all animal life on this planet with an unprecedented LD100 rating.
All that is needed is to engineer a virus to deliver the chemical key to activate this gene systemically.
"A microprocessor... is a terrible thing to waste." --
"A microprocessor... is a terrible thing to waste." --
GeneralEmergency
Actually it is the governments potential sollution:
They can keep uping the social security age requirement due to continued average longevity... I can see it now
I miss the Karma Whores.
I read an interesting article in the latest Popular Science last night (the one with the cover story about raising the russian sub that sank). It was about a professor at Amherst (bleh - go EPHS!) who believes that there is a correlation between infections and cancer. Anyway to make a long story short - he believes that natural selection will eventually provide children with grandparents, because children will rely on the care and wisdom a grandparent can give. Therefore, if a child doesn't have a grandparent, they won't be as successful. I don't know if I agree with this - but some guy with a book thinks so, so I figure I should mention it.
Even if you knew some person (or some other organism) would be healthier if some gene (be it AIF or one of the other executioner genes discovered in the last few years(!) or some completely other gene discovered tomorrow) were different from how it is now, how do you change it? You can't go in with a scalpel and start changing DNA... Can you?
In the article, the authors write "If scientists could ... give a targeted dose of AIF, they might be able to kill the rogue cells in a
cancerous tumour."
But this is a gene, not just a chemical (and there is a difference, isn't there?). Does talk of "a targeted dose of [a gene]" make any sense?
Ron Obvious
The rest is also quite interesting. Read it!
Ron Obvious
Given a greatly extended lifespan, I would stay in school and exit this reality with more degrees than a thermometer, having appreciated the work of the Almighty across the full bandwidth of His handiwork.
Get thee glass eyes, and, like a scurvy politician, seem to see things thou dost not.--King Lear
brain tissue, muscle, dont. And neither does cartilege....
Fight censors!
"Not my manner of thinking but the manner of thinking of others has been the source of my unhappiness." - M
How ever I fail to see how this is going to help people find the fountan of life. We need to be able to regenerate other parts of the body that do not on their own. Cells die all the time, and they need to. If you think your skin is the same you were born with, your very wrong.
Fight censors!
"Not my manner of thinking but the manner of thinking of others has been the source of my unhappiness." - M
What the article is describing is the discovery of a factor that leads to apoptosis apart from the previously elucidated mechanism, which involves a protein (cytochrome c) leaking out from the mitochodria into the cytosol of the cell, where it shouldn't be. Essentially, if the cell detects that, it knows that the there is something terribly wrong, and it should suicide - which is essentially what apoptosis is.
Now, it had been arleady known that there was another mechanism, because if they knocked out the genes responsible for the known mechanism, they could still get apoptosis, though not as readily. This lead to the search of what was causing it. This article describes that discovery, which is AIF.
Interesting work. The reason that this is a more likely candidate that the previous method for fighting cancer is that cytochrome c is a very large, complex protein. Injecting it into cancer cells to initiate apoptosis would be difficult, to say the least. I didn't see enough of the article to see how large AIF is, but I bet it is smaller, and may be easier to get into cells that cystochrome c.
The thing that has me curious is if they could knock out the gene temporarily. They showed that cells were less likely to induce apoptosis under conditions of serum deprivation (starvation). Starving cells is one of the steps toward prepping the nucleus for use in cloning. If they keep more of the cells alive during that process, they might have a better success rate in cloning.
Chew on that one for a while.
If you can't beat them, embrace and extend them.
Screw productivity. Life is about enjoyment
100% Correct. Although reading Slashdot at 2:45 AM is both productive (learnin) and enjoyable (?).
Arathres
stainless steel
Freedom of Choice??? You're on crack. You dont have a choice about dying. Your ass is gonna die one day like it or not. No amount of science (Present Day + few decades) is gonna change that.
Arathres
stainless steel
Im not a doctor, biologist etc.
I think this discovery could be very very useful to science and medicine. Being able to kill off cancer cells and other types of viruses(maybe) this could have huge value to people. The thing I dont understand is this. Common sense leads me to believe that keeping cells alive longer than nature intended might be a bad idea. Cells replenish when they die. The reason they die is they get too old. If cells DID NOT NEED to die, this gene would not exist. Therefore keeping cells alive longer might have BAD consequences.
Why are people obsessed with the fountain of youth. Is there something so wrong with getting old and eventually dying? Make the most of the time you are alive and dont worry about dying. Eventually we all die, accept it, and go do something productive and enjoyable.
Arathres
stainless steel
However, and to quote
Josa, Susin et. al. Nature 410, 549It says quite clearly that this isn't the only way for cells to die. They just do it in a different way that isn't as good. This isn't a wonder chemical/pathway/whatever, it's just an advance in understanding the intricacies of biological systems. This development alone is not going to improve your life at all. Yes, it's interesting, if you're a biologist, but that's all.
I wonder if you could create a virus that would facilitate diffusion of cytochrome c through membranes, or some such (presumably with a time-delay to allow the virus to multiply and spread first). You'd instantly cause every living thing in the area to self-destruct.
Hmm. Scary.
All I ask is a warm bed, a kind word, and UNLIMITED POWER
This gene kills old cells. This is a good thing. Think about this: your old cells never die. So any cell with a faulty replication process will replicate forever. Think cancer on a significantly larger scale.
> You will surely die.
> - Genesis 2:17
It's been obvious to philosophers for centuries that God, or the gods that created this universe, is really more of a supervillian or a pervert who gets off on violence and torture, take your pick. Creating self-aware individuals and sticking them in a world where it's possible to harm each other is pretty sick.
(And your reward, if you live a life of helpfulness according to Christianity? Getting to spend all eternity in a perfect place where such skills are absolutely useless.)
Anyway, anything that flips off God is good in my book. Lightning rods (how dare you thwart the Wrath of God!) and pain killers during birth (God said in pain shall you labor) are noble predecessors. (Indeed, Isaac Asimov pointed out how early preachers spoke against lightning rods as thwarting Zeus^H^H^H^HYaweh's retributive bolts. Soon, only church steeples lacked them. Suddenly, those preacher's churches were the only buildings in town being burned down by the Wrath of God. Not too good if you've built your career on the charlatanism of being God's Own Channeler. Needless to say, rods went up on churches shortly thereafter.)
I am for the complete Trantorization of Earth.
> I pray for your soul, too.
> I hope you will find the mercy in Christ one day.
I am sorry, but this is not a troll, and needs to be said.
There is no greatest infinity. Therefore, there is no most infinite god, and the concept of most powerful infinite being is meaningless.
Therefore, we need only find a more powerful god^H^H^Hinfinite being than God, and ask it for a super-duper, transfinite containment unit and open 'er up on Yaweh.
"The light is green, the trap is clean."
CYA, jerk-who-created-this-universe.
I wonder if Yaweh would squeal if we killed Him slowly. What would go through his infinite mind as finite mortals used far more infinite tools to execute him, deservedly, for this crappy, pain-filled universe? A booming voice comes down from the sky, "Noooooo! Noooo! This can't be happening! Owww! Owwwwwwww! Urrrghkkkk!"
And then Yaweh assumes room temprature.
Imagine the incredible stink from an infinite rotting corpse.
Again, this is not a Troll. These are legitimate ponderings as to how we could possibly end the illogical terror of this existance, as caused by a DEMONSTRABLY EVIL ENTITY.
I am for the complete Trantorization of Earth.
I am currently working on a similar project in my lab. our focus is quite the opposite though, we are investigating a protein that inhibits apoptosis. This protein is the Mcl-1 protein and shows a huge future in upcoming treatments such as the ones listed in the article.
Enjoy your job, make lots of money, work within the law. Choose any two.
... it could potentially open the discovery of a true fountain of youth ....
You will surely die.
- Genesis 2:17
For you are dust, and to dust you will return.
- Genesis 3:19.
For this is the way God loved the world: He gave His one and only Son, that whoever who believes in him should not perish, but have eternal life.
- John 3:16.
For all have sinned, and come short of the glory of God.
- Romans 3:23.
For the wages of sin is death, but the gift of God is eternal life in Christ Jesus, our Lord.
- Romans 6:25.
With apologies to May West, I don't want more years in my life but more life in my years.
Tomorrow is Open.
Secondly, we can insert genes, but not the way we'd like to. I work in a lab where one of our major projects is finding a way to insert a liver enzyme into tumor cells. This would in effect turn the tumor into a tiny liver, so it will metabolize chemotheraputic drugs locally, killing it instead of your liver. The system works great...except we have no good way to deliver the gene to only cancer cells.
You can't just inject naked DNA into the body. Yes, it will be taken up, but most of it will be broken down. Secondly, if the DNA is just a basic plasmid, its copy number and segregation between the new halves of a dividing cell won't work well, and the cell is likely to destroy or silence the DNA. If you use something like a retrovirus, which actually inserts the DNA into the host genome (as HIV does), you have no control over where it will insert. This could end up damaging existing genes, or the body might just target and silence the gene, treating it like an inept virus.
There is another method, tweaking the natural repair system to make small changes in an existing gene. Its a really neat method, but its got a ways to go until its really usable, especially in an organism as opposed to cells in a dish.
So its possible but very difficult. Don't expect it to be commonplace this decade. To continue your analogy, we haven't got scapels yet, just sledgehammers.
Entropy gets everyone.
I don't think that cells die during a stroke or heart attack because they are programmed to die by AIF.
I think it has more to do with reduced blood flow starving the cells of oxygen.
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Infact i remember doing a Cell biology paper way back in 1995 and summarizing several articles on Programmed cell death (apoptosis). And it is NOT usefull for cancer. Cancer cells in general are cells that are divind more rapidly (except for a few slow growing tumors such as small cell carcinoma of the lung etc) and DO NOT respond to the bodies commands/attempts to regulate them. In most cases they do not respond to signals to begin apoptosis.
plasmids
plasmids are CIRCULAR DNA rings that are commonly found in bacteria. Upon injecting small plasmids into bacteria, they are readily taken up into the host dna and replicated.
all you then have to do is extract the result and you have a serum of the resulting DNA/Protein synthesized. But, yes, it is still impractical do most genetherapies at this point.
"the average human would only live about 600 years"
If the average human lives 600 years, how long does the exceptional human live?
More to the point, how do accidents represent an "upper bound"? When I get to 600 without walking in front of a car or falling on a pair of scissors, are the Probability Police going to come hunt me down so I don't "throw off the statistics"?
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324006
Turn off the CNN and learn to investigate the information other people give you..
This statement is false...
Sex and death evolved about the same time, 3/4 a billion years ago. Before that, single cells were immortal until starved, stressed, or eaten. They did exchange some genetic material, but not in the highly organized meiotic fashion of multi-cellular organisms.
...
I wonder if this is a coincidence or inherent coonection between the two.
There are several myths about immortal humans until they discover sex- Adam & Eve, Gilgmesh, Sir Lancelot
So we age becouse we have imperfect copies of cell, that make imperfect copies of themselves. This causes the tissue degenetation.
I believe that making cell live longer, will just make us to have more cells (since it wouldn't stop them from reproducing).
However, the discovery of making them die, can be a huge step on finding the cure of cancer, if them can 'program' the targget cells, leaving the healthy cells alive.
Ladies and gentlemants, Elvis has left the buildnig...