Discover The Secret Of Immortality

Discover The Secret Of Immotality

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Direct Derivation from H2KbtsA58 Transgenic Mice of Conditionally Immortal Myoblasts Able to Differentiate into

To generate cell lines with the above characteristics, J. Morgan and T. Partridge and their colleagues isolated conditionally immortal myoblast cell lines from the limb muscles of 19-d-old embryonic, and 10-d-old and 4-wk-old H-2KbtsA58 transgenic mice (78). Cell growth was sufficiently robust to allow the generation of clones directly by growth at low density. Clones exhibiting a typical myogenic morphology grew readily in the permissive conditions, but not in semipermissive conditions (of 33 C, IFN-y-negative). Of the clones chosen, 14 of 15 readily formed myotubes when grown at high density in nonpermissive conditions. Confluent cultures switched from permissive to nonpermissive conditions showed greatly reduced DNA synthesis and began to form myotubes within 24 h. The number of myotubes continued to increase for the next several days. Some fusion also occurred in permissive conditions if cultures were allowed to become very dense. In both cases, the resultant myotubes expressed...

Cells Grow and Divide

With continuing evolutionary selection for a highly functional body plan, is why today's horseshoe crabs look much as they did 300 million years ago, a time span during which entire mountain ranges have risen or fallen. The Teton Mountains in Wyoming, now about 14,000 feet high and still growing, did not exist a mere 10 million years ago. Yet horseshoe crabs, with a life span of about 19 years, have faithfully reproduced their ancient selves more than half a million times during that period. The common impression that biological structure is transient and geological structure is stable is the exact opposite of the truth. Despite the limited duration of our individual lives, reproduction gives us a potential for immortality that a mountain or a rock does not have.

Replicative Senescence

Barriers to Human Cellular Immortalization. Normal passage of cells is halted at MI unless this barrier is bypassed by p53 and RB inactivation or hTERT expression. These cells can then continue dividing until their telomeres become critically short at M2. hTERT expression or ALT allows telomere length stabilization and cellular immortalization. Pre-senescent cells can be experimentally manipulated to bypass replicative senescence through ectopic expression of certain genes. Expression of hTERT, the catalytic subunit of telomerase is capable of bestowing some but not all primary cells with immortality (29,30). Another mechanism of bypassing this first proliferative barrier is through simultaneous abrogation of the P53 tumor suppressor and retinoblastoma (RB) pathways (28). Expression of viral oncoproteins, such as SV40 large T antigen (31) or human papillomavirus E6 and E7 oncoproteins (32), which bind to and inactivate p53 and RB (33), respectively, offer experimental...

Healing the Cartesian split

Whyte considers this claim to be one of the fundamental blunders made by the human mind, and suggests that one reason why Freud's ideas became so appealing was that, by linking mind indissolubly with body, he was repairing Descartes's dualistic error. Whyte might also have pointed out, although he does not do so, that Freud was an agnostic who had no need to postulate a soul, since he did not believe in the soul's immortality. Freud thought that all mental activity was ultimately driven by unconscious, 'instinctual', physical drives, and thus came close to affirming that the body itself 'thinks', in sharp contrast with Descartes's conception.

Cell Lines versus Primary Cultures

In fact, if cell lines are to be used, one has to carefully assess their tendency to become either hyperproliferative or immortalized since both conditions will make their differentiation into a mature endothelial phenotype either hard or impossible (Table II). Obviously, cell lines offer numerous advantages, including cost-effectiveness and ease of use. However, with the advent of stem cell research, and our increasing understanding of how blood cells differentiate into endothelial cells, one can envision a future where differentiating factors will be used to induce blood-brain barrier properties in omnipotent stem cells. not to divide excessively or take on an immortal pheno-type, as often occurs in cell lines.

Versatile Neuroprotection

Multiple lines of research suggest that PARKIN influences cell death at least in part through caspase-dependent pathways and JNK-dependent signaling. The disparate convergence of possible pathways of protection from such strikingly different stressors such as serum withdrawal, dopamine, ceramide, kainic acid or PARKIN -substrate overexpression suggests that either PARKIN affects some central pathway of cell death or that these studies are confounded by unanticipated variables that influence interpretation. Given the relatively narrow spectrum of cells affected in PARKIN-linked dysfunction in humans, it is improbable, although not impossible, that PARKIN is a critical factor in a pathway central to the life and death of cells. Rather, PARKIN may have off-target effects that influence what might be incorrectly understood as protection or death in cell lines or neurons. For example, PARKIN has been described with tumor suppressive properties, where overexpression of PARKIN slows the...

Replicative Lifespan And Oxidative Stress

Mouse embryonic fibroblasts (MEFs) senesce after vigorous proliferation, and then grow into an immortal cell in normoxia (20 oxygen), whereas human normal fibroblasts never achieve immortality. Parrinello et al. (154) found that MEFs do not senesce in hypoxia (3 oxygen) and that MEFs accumulate more DNA damage in normoxia than hypoxia, and more damage than human fibroblasts in normoxia. These results suggest that human cells have a superior ability to prevent or repair oxidative DNA damage compared to murine cells.

Monoclonal antibodies

In the last 20 years or so, antibody-based therapeutics have mainly focused upon the medical application of monoclonal antibodies. Monoclonal antibody technology was first developed in the mid 1970s, when Kohler and Milstein successfully fused immortal myeloma cells with antibody-producing B-lymphocytes. A proportion of the resultant hybrids were found to be stable, cancerous, antibody-producing cells. These 'hybridoma' cells represented an inexhaustible source of monospecific (monoclonal) antibody. Hybridoma technology facilitates the relatively straightforward production of monospecific antibodies against virtually any desired antigen.

The basis of monoclonal antibody production by hybridoma technology

Immortalized cell (hybridoma) producing antibodies of a single specificity Immortalized cell (hybridoma) producing antibodies of a single specificity Monoclonal antibody technology entails isolation of such B-lymphocytes, with subsequent fusion of these cells with transformed (myeloma) cells. Many of the resultant hybrid cells retain immortal characteristics, while producing large quantities of the monospecific antibody. These hybridoma cells can be cultured long term to effectively produce an inexhaustible supply of the monoclonal antibody of choice. Spleen-derived B-lymphocytes are then incubated with mouse myeloma cells in the presence of propylene glycol. This promotes fusion of the cells. The resultant immortalized antibody-producing hybridomas are subsequently selected from unfused cells by culture in a specific selection medium. Individual hybridomas can be separated from each other by simple dilution and subsequently grown in culture, producing a clone. Individual clones can...

Antigenicity of murine monoclonals

An obvious strategy for overcoming the immunogenicity problem would be the generation and use of monoclonal antibodies of human origin. This is possible but difficult. Human antibody-producing lymphocytes can potentially be rendered immortal by reliable methods for lymphocyte immortalization stability and antibody-producing capacity of resulting immortalized cells. Fusion of human lymphocytes with human lymphoblastoid cell lines is a very inefficient process. Fusion of human lymphocytes with murine myeloma cells lead to very unstable hybrids. Upon fusion, preferential loss of human genetic elements is often observed. Unfortunately, particularly common is the loss of chromosomes 2, 14 and 22, which encode antibody light and heavy chain loci. The production yields of human monoclonals upon immortalization of the human B-lymphocyte (by whatever means) are also low.

The Mitochondrial Theory of Ageing

Mitochondrial Disease Life Expectancy

How much damage mitochondrial DNA suffers as a result of reactive oxygen species generation is still an open question. Studies have shown (Shigenaga et al. 1994) that mitochondria from older animals are morphologically different, and produce more oxidants and less ATP than those from younger ones, but we do not actually know if damage to mitochondria causes ageing, or merely correlates with it. The field of ageing research - what causes ageing and how do we stop, slow, or even reverse it - is an active one. Almost everyone would like to be able to extend his or her life span. Long-lived mutants of the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and even mice have been established in the laboratory, as reviewed by Balaban et al. (2005), but all of these have defective mitochondria, slowing down energy production as well as ageing. These animals also seem to have a reduced reproductive capacity. It seems that reducing generation of reactive oxygen...

The Evolutionary Neurodevelopmental Perspective

Traumatic events shatter these assumptions. Among outpatient veterans who develop PTSD, for example, narcissistic traits are some of the most common (Crosby & Hall, 1992). Far from being invulnerable and immortal, the individual is instead just like everybody else, a speck in a vast cosmos, with random potential for disaster and death. No one is excepted, solid proof that narcissists are not the special persons they believed themselves to be. Among military veterans, Karen (1994) suggests that those with PTSD have fallen far short of the warrior ideal they sought to become. Because narcissists are notorious for idealizing themselves as unusually bright, successful, and admired, we might suppose that traumatic events generally puncture the bubble of these narcissistic fantasies. The individual is brought down to earth in a way that is particularly crushing given the needs of this personality. The persistent question many victims ask, Why me can precipitate feelings of anger and rage...

[18 Toxin Antitoxin Selection for Isolating Heterokaryons and Cell Hybrids

Most studies of the behavior of cell hybrids have employed genetic selection techniques, such as the HAT system,1 to isolate cell fusion products. Although a number of different systems based on this general approach have been extremely useful, there are several practical and theoretical problems associated with their use. For example, only special cell lines that lack the required enzymes can be used. Although in some cases this problem can be overcome by mutagenizing and selecting for cells that carry the necessary defect, this process is often difficult, time consuming, and only conveniently done with immortal cell lines. The cultured proliferative capacity of normal diploid cells2 is limited, so that by the time mutant clones are isolated they only have a few cell divisions left in their lifespan. Some half-selective strategies have been devised where an established immortal cell line is fused to a normal diploid cell type which does not divide in culture, in which it is...

Cell Lines from Transgenic Animals

One way to make certain that all cell lines produced in an experiment contain the same site of integration of the immortalizing gene is to create cell lines from transgenic animals. Since all cells derived from such an animal will share the same insertion site, at least this source of variability in the biology of cell lines will be brought under more stringent control. The possibility of making cell lines from such transgenic animals was recognized from the earliest studies in which immortalizing genes were inserted into the animal genome. For example, the first studies indicating that expression of oncogenes would disrupt normal development (24) showed that mice expressing SV40 TAg under the control of the metallothionein promotor developed tumors of the choroid plexus and showed that cell lines could be isolated from the transformed tissue. Studies in which the 5' regulatory sequences of the insulin gene were used to control the in vivo expression of SV40 TAg showed that it was...

Application to Schizoid Schizotypal and Avoidant Personality Disorders

Evolutionary psychologists have not yet directly addressed the issue of personality disorders and aging, but numerous general evolutionary theories of aging exist. Kirkwood (2000) suggested that aging and senescence were the price humans paid for their evolutionary success. Indeed, our somatic cells age while our genes have the potential to be immortal. Bouchard and Loehlin (2001) observed that evolutionary psychologists, although addressing the evolutionary adaptiveness of personality disorder traits in the ancestral environment, have not yet adequately studied personality disorders in the evolutionary perspective in regards to aging.

Viruses and Animal Tumors

The properties of the transformed cells in culture are similar to those of tumor cells in the body. Transformed cells do not respond to signals that limit their growth. Thus, whereas normal cells grow as a single or monolayer on a glass surface, transformed cells grow in multiple layers. Also, normal cells go through only a limited number of cell divisions and then die. In contrast, transformed cells growing in tissue culture multiply indefinitely. They are immortal. Further, normal cells stick tightly to the surface of the glass culture dish, whereas transformed cells readily detach from the surface, a phenomenon analogous to metastasizing in the body. Also, when transformed cells in culture are injected into animals, most, but not all, cause tumors. bacterial transformation, p. 203

Anima animus and shadow

In the course of analysis of their dreams, patients would encounter various typical 'primordial images' or archetypes which are experienced as being of profound significance. For example, the primordial image of the opposite sex, which in men is named the 'anima', may be someone resembling Rider Haggard's 'She'. The aptly named 'She' is not only spectacularly beautiful, but also an immortal priestess with access to divine wisdom. 'She' is not an actual woman, but an image of the eternal feminine. The phenomenon of being in love, which Freud referred to as 'the normal prototype of the psychoses',(3) consists in projecting an anima image upon the beloved, who may in reality be unremarkable in the eyes of everyone except those of the deluded lover. Film stars and princesses are often similarly perceived. The primordial image of the opposite sex in women is named 'animus', and is projected in similar fashion upon film stars from Valentino to Cary Grant. The image is often at odds with the...

Cell Differentiation

The least differentiated and most prolific cells within the body are called stem cells. In a healthy organism, stem cells act as a source of new cells during tissue repair, as illustrated in Figure 3.1 (adapted from reference 1). As shown in the figure, stem cells are capable of both self-renewal (self-replacement) and clonal expansion and so are virtually immortal. Not surprisingly, stem cells are present in high numbers in tissues that constantly renew their population, such as the bone marrow and intestinal lining. Bone marrow cells have a turnover rate of approximately five days, as opposed to several years for some vascular cells. Although stem cells in normal tissues have a high ability to proliferate, their proliferation is tightly regulated, occurring only under specific circumstances.

Available Assays

Telomerase is an enzyme that normally maintains the length of the telomeres in stem cells. Interestingly, telomerase is upregulated in most malignant cells and is thought to be necessary for the maintenance of the immortal phenotype that typifies malignant cells. Because telomerase is over-expressed in almost all malignancies but not in most normal tissues, it has been suggested that telomerase may be a good marker for the presence of malignant cells in various cyto-logic specimens, including urine and oral washings.

Consequences

Assuming my argument is correct, and that people are computational machines, does that mean that there is no such thing as the soul and, in particular, the immortal soul Does it mean that there is nothing valuable about a person, since a person is just a machine Does it mean that everything is permitted Can there be something that a machine ought to do or not do How do you get from the description of the machine's behavior what is to a commandment what ought to be

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Stem cells in plants are located in meristems, populations of undifferentiated cells found at the tips of growing shoots. Shoot apical meristems (SAMs) produce leaves and shoots, and of course more stem cells that constitute the nearly immortal meristems. Meristems can persist for thousands of years in long-lived species such as redwood trees and bristlecone pines. As a plant grows, the cells left behind the meristems are encased in rigid cell walls and can no longer grow. SAMs can split to form branches, each branch with its own SAM, or be converted into floral meristems (Figure 22-6). Floral meristems give rise to the four floral organs sepals, stamens, carpels, and petals that form flowers. Unlike SAMs, floral meristems are gradually depleted as they give rise to the floral organs.

Methylmercury

Perhaps one of the most significant considerations is that greater amounts of stored mercury will result in greater amounts of released mercury when detoxification mechanisms are later stimulated. Many people do not even concern themselves with toxins and detoxification until they get a little older and begin to realize that they won't live forever. For this reason, the reemergence of the stored mercury as the body detoxifies will be even more toxic clinically in these people, because their immune systems will typically have been stressed and traumatized for a longer time, and immune protection against toxins will be lessened.

Molecular Changes

Multiple intracellular protein networks exist downstream of growth factor receptors that can become constitutively active in a mutated state, conferring a growth-inducing effect. As discussed above, introduction of one of these aberrant signals, H-RAS, turns an activating switch on and facilitates malignant transformation to previously immortalized human and rodent primary cells. (See Chapter 7). Both telomere length and maintenance are associated with human cell lifespan, genetic instability, senescence, immortalization, and transformation. In approximately 90 of human tumors, telomere maintenance and replicative immortality may be achieved through activation of telomerase the remaining tumors may be maintained through alternative lengthening of telomeres (ALT), a telomerase-independent mechanism (134). Interestingly, studies examining malignant transformation in ALT cells lacking P53 and RB function, but expressing oncogenic RAS, confirm that malignant transformation is impossible...

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