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Genetics: Gene Expression - Gene Expression And Life Span

age aging aging sir2 yeast silencing

No single change in gene expression has yet been shown to be responsible for limiting or extending the life span of an organism (or even a tissue, for that matter). However, manipulation of general regulators of gene expression has been shown to alter life span, at least in model organisms. Perhaps the best example of this is the SIR2 protein, which is conserved from yeast to mammals and is responsible for the heterochromatic silencing of genes. In yeast, inactivation of the SIR2 gene results in defective gene silencing, increased illegitimate recombination at the repetitive loci that encode rRNAs, and a shortening of life span. Conversely, an additional copy of the yeast SIR2 gene, which presumably results in more efficient silencing and suppression of recombination, extends yeast life span. Of greater relevance to complex eukaryotes, an additional copy of the SIR2 gene in the model organism Caenorhabditis elegans, a multicellular nematode, also extends life span. SIR2 requires NAD (nicotinamide adenine dinucleotide) as a cofactor. Thus, SIR2 may act to coordinate energy utilization, recombination, and control of gene expression, all of which may strongly influence life span.

JUDITH CAMPISI

BIBLIOGRAPHY

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