Cell senescence is the gradual deterioration of cell morphology, proliferation and physiology at a normal condition. The word senescencecan refer either to cellular senescence or to senescence of the whole organism. It is commonly believed that cellular senescence underlies organismal senescence.

Cell senescence does not mean organism aging. Cell senescence is throughout the whole process of organism development. Together with apoptosis, cell senescence constantly happens in organism, with newborn cells replacing senescenced cells. While organism aging is the process of becoming older. In humans, ageing represents the accumulation of changes in a human being over time, including physical, psychological, and social changes. In a word, cell senescence is the basis of organism aging.

(1) Moisture in cell is decreased, and cell will shrink.

(2) Lipofuscin deposition

(3) Nucleus pycnosis, euchromatin decrease, transcription activity decrease.

(4) Cell membrane thickens, with mobility decreasing while permeability and fragility increasing.

(5) Number of Mitochondria decreases, with size of cell increase and structure disorganized.

(6) Number of Endoplasmic reticulum decreases; Golgi complex scatters; number of lysosome increases and the volum enlarges.

(1) Both biosynthesis and metabolic rate slow down

(2) Enzymatic activity decreases, especially lysosome.

(1) Genetic Program Theory

This theory focuses on the function of the genetic gene to the gene. It is believed that the death of cell and organism is our biological nature, and is the program of life cycle. Senescence is controled by the senescence gene which will not be expressed until the cell is old enough. Before it is expressed, some other genes deactivate the senescence gene. When the deactivated gene decreased in depression, and reduce in number until the concentration is lower than the senescence gene, the senescence gene will express.

(2) Error Theory

Ultraviolet light, radiation, toxins and mutagenic can cause DNA damage. Once the damage can not repair or mistaken repair, the cell transcription or error translation may goes wrong. With the age increases, the error increased transcription, and the accumulated error proteins and enzymes will inevitably affect the cell function and lead to aging and cell death.

(3) Telomere theory

The cells's senescence is caused by the shortening of the teleomere sequences. The structure of human's telomeres is the highly repetitive TTAGGG sequences of the end of chromosomes. Cell aging happens when it is short. Due to the RNA primer, DNA polymerase cannot complete a DNA replication of chromosomal end; finally the telomere's length will be shortened along with the increasing of the cell division. When it is shorter than the threshold value, the cell gets into aging. Clone sheep Dolly's cell telomere is 20% shorter than that of the other sheep at the same age. Finally it is suffered geriatric disease for less than 7 years, and given euthanasia.

Telomere can maintain the length constantly when cell division. The continuous porliferation of the germ-line cells is because the cell can express telomere. Telomere is the nuclear protease made of RNA and protein, whose RNA can serve as a kind of template and transcribe a segment of telomere though reverse transcriptase to link to the end of the chromosome thelomere, so that thelomere will not be shorten.

(4) Free radical theory

The body will produce free radical in the metabolic process. In human's body, oxygen radical is of 95% in free radical, and 5% is non-oxygen radical. Oxygen radical is the oxygen molecules lack of an electron, with high flexicity, which can attack large molecules through strong oxidation and cause cell damage and degenerative changes in the body.

There are free radical scavengers in the body so that the production and cleaning of the free radical keeps in a dynamic balance. They mostly are antioxidant, such as superoxide dismutase (SOD), catalase(CAT), Vit C, Vit E, and β-carotene. With the growth of the age, the dynamic balance is broken, and the number of free radicals in cells is increased. At the same time, the ability of scavenging free radicals is decreased, and the excessive free radicals will cause all kinds of damage accumulating and aging.

Some cosmetics is added superoxide dismutase (SOD) is to reduce the oxygen free radicals and protect the skin.

Progeria (Hutchinson-Gilford progeria syndrome, HGPS, OMIM176670) is an extremely rare genetic disorder where in symptoms resembling aspects of aging are manifested at a very early age. A child suffered progeria looks like old man, and his body's aging is 5 to 10 times quicker than normal aging speed, the same as his organ.

A family in Hezhou, Guangxi suffered from HGPS. There are 5 members in the family where parents do not express HGPS, while 3 children have typical HGPS symptom: balding, exophthalmos, pointed nose, small mandible, short stature, underweight, buckling of both hands, body skin sclerosis, lipodystrophy, exposed scalp vein, etc.

HGPS is caused by gene mutation of LMNA gene which is located in 1q21.1-21.3 with 12 exon, coding nuclear lamina protein lamin A and lamin C involved in building nuclear lamina. The result of gene mutations detection in Hezhou's family shows that the point C1579T of the 9th exon of LMNA gene mutation resulted in the change of the 527th amino acid which basic arginine changed into neutral cysteine. In that family, the three children are R527C homozygous mutation while the parents are R527C heterozygous mutation.

Cell death is the irreversible ending of a cell, including necrosis and apoptosis.

Necrosis is a non-physiological process that occurs as a result of infection or injury. Necrosis is cell death caused by external factors such as trauma or infection, and occurs in several different forms.

Characteristics:

(1) Necrosis is caused by some environment factors, such as hyperpyrexia, ischemia, mechanical trauma, toxication, and microorganism intoxication, et al.

(2) Cell swell, and permeability of membrane increase.

(3) Lysosome broke down and enzyme was released; cellular content is released, and cytolyse.

(4) Cell died massively, leading to severe inflammation of surrounding tissues.

Apoptosis (programmed cell death (or PCD)) is cell death mediated by an intracellular program. Apoptosis is carried out in a regulated process, which usually confers advantage during an organism's life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and metazoa (multicellular animals) tissue development.

Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNAfragmentation. It is now thought that - in a developmental context - cells are induced to positively commit suicide whilst in a homeostatic context; the absence of certain survival factors may provide the impetus for suicide. There appears to be some variation in the morphology and indeed the biochemistry of these suicide pathways; some treading the path of “apoptosis”, others following a more generalized pathway to deletion, but both usually being genetically and synthetically motivated. There is some evidence that certain symptoms of “apoptosis” such as endonuclease activation can be spuriously induced without engaging a genetic cascade, however, presumably true apoptosis and programmed cell death must be genetically mediated. It is also becoming clear that mitosis and apoptosis are toggled or linked in some way and that the balance achieved depends on signals received from appropriate growth or survival factors.

Morphological and biochemical changes

(1) Cell shrinkage and rounding occur because of the retraction lamellipodia and the breakdown of the proteinaceous cytoskeleton by caspases.

(2) The cytoplasm appears dense, and the organelles appear tightly packed.

(3) Chromatin undergoes condensation into compact patches against the nuclear envelope (also known as the perinuclear envelope) in a process known as pyknosis, a hallmark of apoptosis.

(4) The nuclear envelope becomes discontinuous and the DNA inside it is fragmented in a process referred to as karyorrhexis. The nucleus breaks into several discrete chromatin bodies or nucleosomal units due to the degradation of DNA.

Molecular mechanisms

The starting of apoptosis is connecting to a series of gene's activation, regulation and expression. For mammalia, the gene is caspase. Caspase, is a kind of cascade reaction, to activate endonuclease, to make DNA degradation, and finally comes into being apoptosis body.

Mitochondrion produces free radicals through respiration, which is also participated in the apoptosis process. Once mitochondrion is damaged, mitochondrial membrane permeability has changed and released the cytochrome C to activate caspase and finally caused the cascade reaction of apoptosis.

Physiological significance

(a)In the process of individual development, the formation of many organs is the result of the cell apoptosis.

① The formation of the lumen, such as trachea, esophagus, and blood vessels, not because of the differentiation of the cells, but because of the apoptosis.

② The gingiva and lip separate.

③ The separation of the fingers and toes

(b)Control the number of the cell

About 50% of neuron apoptosis will happen in the process of development of the nervous system. The body regulates the number of neurons through apoptosis to meet with the number of the target cells.

©Removes the aging, damaged, and “redundant” cells

① The development, differentiation and maturation of lymphocytes are always accompanying the apoptosis.

② Being attacked by virus, the cells will prevent the virus replicating and abusing through apoptosis.

(d)Produce non-organelles cell, such as erythrocyte.

A. The organs will develop malformation, such as palmature, long tail, etc.

B. When leukocyte apoptosis fails, it may cause leukocyte accumulation and leads to leukaemia.

A. Neuron occurred excessive apoptosis may cause stroke or senile dementia, etc.

B. Excessive cardiomyocytes apoptosis may cause heart failure.

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