A Healthy immortal body is coming closer

[Bob]

Apoptosis - programmed Cell Death

Within the nucleus of the Cell, there are Chromosomes, or information packets containing further sets of instructions called GENES - which are made of/from DNA

DNA - The DNA in one's cells is packaged into 46 chromosomes in the nucleus. As well as being a naturally helical molecule, DNA is supercoiled using enzymes so that it takes up less space.

Try holding a piece of string at one end, and twisting the other. As you add twist, the string creates coils of coils; and eventually, coils of coils of coils.

One's DNA is arranged as a coil of coils of coils of coils of coils! (TIGHT PACKING.)

This allows the 3 billion base pairs in each cell to fit into a space just 6 microns across.

If you stretched the DNA in one cell all the way out, it would be about 2m long and all the DNA in all your cells put together would be about twice the diameter of the Solar System. THERE ARE ONLY TWO STRANDS in DNA.

CHROMOSOME - In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46.

Twenty-two of these pairs, called autosomes, look the same in both males and females.

The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.

GENE - Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.)

The journey from gene to protein is complex and tightly controlled within each cell.

It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression.

NB: ALL ACTIONS ARE CONTROLLED BY THE GENES.

GENES are sensitive to external AND internal chemical and electrical stimulation.

During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties.

The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. (Cytoplasm, the semi-liquid gel within the cell in which the nucleus resides).

Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm.

The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for one particular amino acid. (Amino acids are the building blocks of proteins.)

A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time.

Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid).

The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology.

Separation of GENES into FUNCTION -

Each cell expresses, or turns on, only a fraction of its genes.

The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation.

Gene regulation is an important part of normal development.

Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example.

Gene regulation also allows cells to react quickly to changes in their environments.

Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood.

Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA).

Signals from the environment or from other cells activate proteins called transcription factors.

These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.

Induction of Apoptosis:

There are GENES specifically designed to terminate or kill the cell. There are specific categories, where attempts to repair damage happen first. When damage repair cannot be adequately accomplished the "death receptors" activate.

A cell has to normally TURN OFF the death sequence and a properly functioning cell WILL continually turn OFF its own death.. (Anti-Apoptosis genes)

When it cannot due to excessive unrepairable damage to the DNA, the death receptors start to function to call up the steps needed to shut-down dna replication.. FLAGS appear to the other cells in the body responsible for cleaning up debris (damaged cellular material).

Death Domain Receptors: CRADD, FADD, TNF, TNFRSF10B (DR5).

DNA Damage: ABL1, CIDEA, CIDEB, TP53, TP73.

Extracellular Signals: CFLAR (CASPER), DAPK1, TNFRSF25 (DR3).
Other: BAD, BAK1, BAX, BCL10, BCL2L11, BCLAF1, BID, BIK, BNIP1, BNIP3, BNIP3L, CASP1 (ICE), CASP10 (MCH4), CASP14, CASP2, CASP3, CASP4, CASP6, CASP8, CD27 (TNFRSF7), CD70 (TNFSF7), DFFA, FAS (TNFRSF6), FASLG (TNFSF6), GADD45A, HRK, LTA (TNFB), NOD1 (CARD4), PYCARD (TMS1/ASC), TNFRSF10A, TNFRSF9, TNFSF10 (TRAIL), TNFSF8, TP53BP2, TRADD, TRAF3.

Anti-Apoptosis: AKT1, BAG1, BAG3, BAG4, BAX, BCL2, BCL2A1 (Bfl-1/A1), BCL2L1 (BCL-X), BCL2L10, BCL2L2, BFAR, BIRC3 (c-IAP1), BIRC6, BIRC8, BNIP1, BNIP2, BNIP3, BNIP3L, BRAF, CD27 (TNFRSF7), CD40LG (TNFSF5), CFLAR (CASPER), DAPK1, FAS (TNFRSF6), HRK, IGF1R, MCL1, NAIP (BIRC1), NOL3, RIPK2, TNF, XIAP (BIRC4).

Regulation of Apoptosis:
Negative Regulation: BAG1, BAG3, BAG4, BCL10, BCL2, BCL2A1 (Bfl-1/A1), BCL2L1 (BCL-X), BCL2L10, BCL2L2, BFAR, BIRC3 (c-IAP1), BIRC6, BIRC8, BNIP1, BNIP2, BNIP3, BNIP3L, BRAF, CASP3, CD27 (TNFRSF7), CD40LG (TNFSF5), CFLAR (CASPER), CIDEA, DAPK1, DFFA, FAS (TNFRSF6), IGF1R, MCL1, NAIP (BIRC1), NOL3, TP53, TP73, XIAP (BIRC4).
Positive Regulation: ABL1, AKT1, BAD, BAK1, BAX, BCL2L11, BCLAF1, BID, BIK, BNIP3, BNIP3L, CASP1 (ICE), CASP10 (MCH4), CASP14, CASP2, CASP4, CASP6, CASP8, CD70 (TNFSF7), CIDEB, CRADD, FADD, FASLG (TNFSF6), HRK, LTA (TNFB), NOD1 (CARD4), PYCARD (TMS1/ASC), RIPK2, TNF, TNFRSF10A, TNFRSF10B (DR5), TNFRSF25 (DR3), TNFRSF9, TNFSF10 (TRAIL), TNFSF8, TP53, TP53BP2, TRADD, TRAF2, TRAF3, TRAF4.

Both positive and negative regulation steps provide a type of ACTIVE FEEDBACK to keep the repair and killing mechanisms in balance.

It should be obvious that when the feedback mechanisms are set out of rhythm, that issues can arise.. It is in these feedback mechanisms where 'tampering' has happened, leading to a body "life span" at best on a programmed average of about 100 years.

I will get further into the specific gene sequences in the repair and regulatory genes later in the thread.

[bearcow]

quickly my 2 cents here, true immortality cannot be achieved by upgrading the genetic sequences. If the the elemental forces in the the body are imbalanced, physical disease will eventually be the result. This is beyond the scope of genetics. If the elemental forces that constitute your being are in complete balance, you are already a immortal, and have naturally upgraded your genetic coding. I do however believe our lifespans can be extended significantly by genetic means, so that we live lifespans like Noah did back in the time of the flood.

[Bob]

There are 84 key genes involved in programmed cell death.

Apoptosis plays a critical role in normal biological processes requiring cell removal including differentiation, development, and homeostasis.

Stress responses (such as heat shock, ischemia, unfolded proteins, and viral infection) cause badly damaged cells to undergo apoptosis.

In cell culture, growth factor withdrawal and many known experimental compounds have a similar effect.

An acquired defect in apoptosis activation often leads to uncontrolled cell growth, oncogenesis, and cancer. (KEY UNDERSTANDING HERE)

Ligand-bound tumor necrosis factor (TNF) receptors initiate apoptosis by recruiting FADD and other death domain adaptor proteins that then recruit and activate caspases.

Environmental stresses trigger BCL2 protein oligomerization and insertion into the mitochondrial membrane, releasing APAF1 and other CARD family members that also oligomerize to recruit and activate caspases.

Caspases promote a proteolysis cascade that degrades cellular protein targets, while the IAP protein family directly inhibits caspases. (This is an example of the positive/negative FEEDBACK mechanism at work).

This array includes TNF ligands and their receptors, members of the bcl-2, caspase, IAP, TRAF, CARD, death domain, death effector domain, and CIDE families, as well as genes involved in the p53 and DNA damage pathways.

[Bob]

Caspases and the apoptosome - Killers kept under control

The caspases are a family of proteins that are one of the main executors of the apoptotic process.

They belong to a group of enzymes known as cysteine proteases and exist within the cell as inactive pro-forms or zymogens.

Keywords, exist within the cell AS INACTIVE proto-forms.

These zymogens can be cleaved to form active enzymes following the induction of apoptosis. So splitting them off, allows them to then become potentially ACTIVATED.. Whence activated, the cascade reactions start to rip apart the cell (and of course facilitate cellular death). Stopping this from happening would be ONE pathway for cellular immortallizing.

Induction of apoptosis via death receptors typically results in the activation of an initiator caspase such as caspase 8 or caspase 10.

These caspases can then activate other caspases in a cascade.

This is where the DEATH sequence is actively promoting the disintegration of the DNA and other cellular proteins back into basic amino acids (that can potentially be recycled).

This cascade eventually leads to the activation of the effector caspases, such as caspase 3 and caspase 6.

These caspases are responsible for the cleavage of the key cellular proteins, such as cytoskeletal proteins, that leads to the typical morphological changes observed in cells undergoing apoptosis.

The Apopto-some

The program packet in other words, or a set of instructions and feedback mechanisms to activate various sub-routines to control how to kill.

There are a number of other mechanisms, aside from activation of the death receptors, through which the caspase cascade can be activated.

Granzyme B can be delivered into cells by cytotoxic T lymphocytes and is able to directly activate caspases 3, 7, 8 and 10.

The mitochondria are also key regulators of the caspase cascade and apoptosis. Release of cytochrome C from mitochondria can lead to the activation of caspase 9, and then of caspase 3. This effect is mediated through the formation of an apoptosome, a multi-protein complex consisting of cytochrome C, Apaf-1, pro-caspase 9 and ATP.

Caspases and chromatin breakdown

One of the hallmarks of apoptosis is the cleavage of chromosomal DNA into nucleosomal units.

The caspases play an important role in this process by activating DNases, inhibiting DNA repair enzymes and breaking down structural proteins in the nucleus.

This processes is illustrated below:

1) Inactivation of enzymes involved in DNA repair.

The enzyme poly (ADP-ribose) polymerase, or PARP, was one of the first proteins identified as a substrate for caspases. PARP is involved in repair of DNA damage and functions by catalyzing the synthesis of poly (ADP-ribose) and by binding to DNA strand breaks and modifying nuclear proteins. The ability of PARP to repair DNA damage is prevented following cleavage of PARP by caspase-3.

2) Breakdown of structural nuclear proteins.

Lamins are intra-nuclear proteins that maintain the shape of the nucleus and mediate interactions between chromatin and the nuclear membrane. Degradation of lamins by caspase 6 results in the chromatin condensation and nuclear fragmentation commonly observed in apoptotic cells.

3) Fragmentation of DNA.

The fragmentation of DNA into nucleosomal units - as seen in DNA laddering assays - is caused by an enzyme known as CAD, or caspase activated DNase. Normally CAD exists as an inactive complex with ICAD (inhibitor of CAD). During apoptosis, ICAD is cleaved by caspases, such as caspase 3, to release CAD. Rapid fragmentation of the nuclear DNA follows.

And there you have it, a cell is taken apart, reduced to bare components, and quite "dead".