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13506965 Aging Theories and Potential Therapies 2

13506965 Aging Theories and Potential Therapies 2

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Published by Abdullah Hashemi

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Published by: Abdullah Hashemi on Jun 23, 2010
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03/24/2013

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Running a cell is a complex affair.RNA and proteins have to be synthe-

sized on a regular basis to maintain and run the cell’s machinery (see

chapter 8 for a cell primer).Production ofproteins,either for enzymes

or structural materials,occurs in a two-step process:transcription of

the gene to produce mRNA,followed by translation ofthe message to

produce the protein.For cells that are actively dividing,a third step,

replication ofthe DNA,precedes the other two.Errors can occur all

along the way;when they do,defective genes,mRNA,and proteins are

produced.The error catastrophe theory,first proposed in the 1960s,

suggests that over time,the number oferrors build up to a catastrophic

level leading to the death ofthe cell and,possibly,the entire organism.

Soon after this theory was proposed,many scientists conducted

experiments that attempted to force a buildup oferrors to see how the

cells would cope with it.Bacteria were grown on a medium containing

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defective amino acids to maximize the error frequency ofprotein syn-

thesis.Similar experiments were conducted on fruit flies (Drosophila)

and mice,both ofwhich were given food containing defective amino

acids.To everyone’s surprise,these experiments had no effect on the

bacteria’s or animal’s health,vigor,or life span.Somehow the cells were

able to avoid an error catastrophe.Today we understand why those

experiments failed:Cells have elaborate repair systems and strategies

that detect and destroy defective molecules.Ifa defective protein is syn-

thesized,it is quickly broken down and replaced with a normal copy.

Only in cases where the repair systems have been damaged would an

error catastrophe occur (see Werner’s syndrome in chapter 5).

In its original formulation,the error catastrophe theory focused on

protein synthesis,which apparently can tolerate a high error frequency.

Consequently,many scientists began to wonder iferrors in the genome,

or possibly a defective regulation ofthe genes,might be responsible for

the aging process.After all,cells avoid an error catastrophe at the trans-

lational level because they can always try again with a fresh mRNA from

a good gene.But ifthe genes themselves are damaged,or programmed

for senescence,the outcome would be a gradual decline in cell vigor and

the eventual death ofthe organism.

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