Senescence Theories Of Aging Evolutionary Theories

Cellular senescence is a phenomena where isolated cells demonstrate a limited ability to divide in culture. Organismal senescence is the aging of organisms.

right Supercentenarian Ann Pouder (8 April, 1807 - 10 July, 1917) photographed on her 110th birthday. A heavily lined face is common in human senescence. Organismal aging is generally characterized by the declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. Because of this, death is the ultimate consequence of aging.

1 Theories of aging

The process of senescence is complex, and may derive from a variety of different mechanisms and exist for a variety of different reasons. Senescence is a universal biological phenomea, at least amongst eukaryotic organisms. Yet the average lifespan within and between species can vary greatly. This suggests that both genetic and environmental factors contribute to aging.

Theories that explain senescence can generally be divided between the programmed and error theories of aging. Programmed theories imply that aging is regulated by biological clocks operating throughout the life span. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance, repair and defense responses. Error theories blame environmental insults to living organisms that induce cumulative damage at various levels as the cause of aging (e.g., DNA damage, oxygen radicals, cross-linking).

Gerontologist also theorise that one potential cause of senescence is the accumulation of mutationThis article is about mutation in biology, for other meanings see: mutation (disambiguation). Mutations are permanent, transmissible changes to the genetic material (usually DNA or RNA) of a cell. Mutations can be caused by copying errors in the genetic ms in DNADeoxyribonucleic acid DNA is a nucleic acid which carries genetic instructions for the biological development of all cellular forms of life and many viruses. DNA is sometimes referred to as the molecule of heredity as it is inherited and used to propagate, eventually leading to the progressive loss of key genes. Another is the shortening of telomereA telomere is a region of highly repetitive DNA at the end of a chromosome, which functions as an aglet. Every time linear eukaryotic chromosomes are replicated, the DNA polymerase complex stops several hundred bases before the end; if it were not for tels in the process of DNA replication during cell division.

Scenescence is studyed in geratology which is the branch of science involved with the aging process.

2 Evolutionary theories

One view is that it is due to a particular DNADeoxyribonucleic acid DNA is a nucleic acid which carries genetic instructions for the biological development of all cellular forms of life and many viruses. DNA is sometimes referred to as the molecule of heredity as it is inherited and used to propagate programming that has the sole purpose to "clean" Earth from old genes and assure offspring better living conditions through benign mutations.

One possible mechanism may be "senescence geneDNA and to a chromosome (right). Introns are regions often found in eukaryote genes which are removed in the splicing process: only the exons encode the protein. This diagram labels a region of only 40 or so bases as a gene. In reality many genes are muchs". Genes which have a deleterious effect on individual's fitnessFitness is a very central concept in evolutionary theory. It measures the capability of an individual of certain genotype to reproduce, and usually it equals to the proportion of the individual's genes of all the genes of the next generation. If there are are selected against by natural selectionAlternative meaning Natural Selection (computer game . Natural selection is the primary mechanism within the scientific theory of evolution, i. it alters the frequency of alleles within a population. It was first proposed as the main mechanism of evolutio. Mutations in these genes which postpone the deleterious effect of the gene to a later time in individual's life history reduce the effect of natural selection to the gene, because the selection has less time to act on it. If the gene doesn't have a negative effect until after the individual has reproduced, the gene may escape natural selection altogether, because when selection starts to affect the gene, it has already propagated to the next generation.

An alternative view of looking at this question is: why do humans live so long? No other primate has such an extended post-reproductive phase of life. The "grandmothering theory" of evolution holds that because humans can teach their young, there was an evolutionary advantage for groups of humans who had a few older survivors to teach and care for the young. There is no particular evidence for this theory.

3 Gene regulation

A number of genetic components of aging have been identified using model organisms, ranging from the simple budding yeastSaccharomyces cerevisiae is a yeast used in both baking and brewing. Yeast are a group of unicellular fungi a few species of which are commonly used to leaven bread and ferment alcoholic beverages. Most yeasts belong to the division Ascomycota. A few yeas Saccharomyces cerevisiae to worms such as Caenorhabditis elegans and fruit flies. Study of these organisms has revealed the presence of at least two conserved aging pathways.

One of these pathways involves the gene Sir2, a NAD+-dependent histone deacetylase. In yeast, Sir2 is required for genomic silencing at three loci: the yeast mating loci, the telomeres and the ribosomal DNA (rDNA). Yeast replicative aging is caused by homolgous recombination between rDNA repeats; excision of rDNA repeats results in the formation of extrachromosomal rDNA circles (ERCs). These ERCs replicate and preferentially segregate to the mother cell during cell division, and are believed to result in cellular senescence by titrating away essential nuclear factors. While ERCs are not believed to contribute to aging in higher organisms such as human, extrachromosomal circular DNA (eccDNA) has been found in worms, flies and humans. The role of eccDNA in aging is unknown.

Despite the lack of a connection between circular DNA and aging in higher organims, extra copies of Sir2 are capable of extending the lifespan of both worms and flies. The mechanisms by which Sir2 homologues in higher organisms regulate lifespan is unclear, but the human SIRT1 protein has been demonstrated to deacetylate p53, Ku70, and the forkhead family of transcription factors.

Other genes regulate aging in yeast by increasing the resitance to oxidative stress. Superoxide dismutase, a protein that protects aginst the effects of mitochondrial free readicals, can extend yeast lifespan in stationary phase when overexpressed.

In higher organims, aging is likely to be regulated in part through the insulin/IGF-1 pathway. Mutations that affect insulin-like signaling in worms, flies and mice are associated with extended lifespan.

4 Cellular senescence

Lately the role of telomeres has aroused general interest, especially with a view to the possible genetically adverse effects of cloning. The successive shortening of the chromosomal telomeres with each cell cycle is also believed to influence the vitality of the cell, thus contributing to aging. There have, on the other hand, also been reports that cloning could alter the shortening of telomeres.

5 Chemical damage

It is also suggested that damage to long-lived biopolymers, e.g., structural proteins and DNA, caused by ubiquitous chemical agents in the body, such as oxygen and sugars, are in part responsible for aging. The damage can include breakage of biopolymer chains, cross-linking of biopolymers, or chemical attachment of unnatural subtituents ( haptens) to biopolymers.

Under normal aerobic conditions, approximately 4% of the Oxygen metabolized by mitochondria is converted to superoxide ion which can subsequently be converted to hydrogen peroxide, hydroxyl radical and eventually other reactive species including other peroxides and singlet oxygen, which can in turn generate free radicals capable of damaging structural proteins and DNA. Certain metal ions found in the body, such as copper and iron, may participate in the process. (In Wilson's disease, a hereditary defect which causes the body to retain copper, some of the symptoms resemble accelerated senescence.) These processes are termed oxidant damage and are the target of the currently popular nutritional antioxidants.

Sugars such as glucose and fructose can react with certain amino acids such as lysine and arginine and certain DNA bases such as guanine to produce sugar adducts, in a process called glycation. These adducts can further rearrange to form reactive species which can then cross-link the structural proteins or DNA to similar biopolymers or other biomolecules such as non-structural proteins. People with diabetes, who have elevated blood sugar, develop senescence-associated disorders much earlier than the general population, but can delay such disorders by rigorous control of their blood sugar levels. There is evidence that sugar damage is linked to oxidant damage in a process termed glycoxidation.

Chemical damage to DNA can lead to mutations (see above). Chemical damage to structural proteins can lead to loss of function; for example, damage to collagen of blood vessel walls can lead to vessel-wall stiffness and thus hypertension, and vessel wall thickening and reactive tissue formation ( atherosclerosis); similar processes in the kidney can lead to renal failure.

6 Reliability theory

Suggests that biological systems start their adult life with a high load of initial damage.

7 Neuro-endocrine-immuno theories

Senescence may also simply be a result of wear and tear overwhelming repair mechanisms. It is also possible that senescence is a mechanism to control the development and spread of cancer; if cells have built-in limits to how many times they can replicate, they must somehow overcome this before they can spread indefinitely.

8 Misc

Recently, early senescence has appeared as a possible unintended outcome of early cloning experiments, notably in the case of Dolly the sheep.

A set of rare hereditary ( genetic) disorders, each called progeria, has been known for some time. Sufferers exhibit symptoms resembling accelerated aging, including wrinkled skin. The cause of Hutchinson–Gilford progeria syndrome was reported in the journal Nature in May 2003. This report suggests that DNA damage, not oxidative stress, is the cause of this form of accelerated aging.

Artificially-induced senescence, as a means of control over artificially-created humans, or androids, is a central plot motivation in the renowned 1982 science fiction film " Blade Runner", loosely based on Philip K. Dick's ( 1968) novel " Do Androids Dream of Electric Sheep?".

Centenarian is a person who has attained the age of 100 years or more.

Smoking cigarettes accelerates senescence, or leads to premature senescence. Smokers age faster than non-smokers.

9 External links

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