One part of the answer to this question may involve the yeast nuclear protein Sir2, according to a study in tommorow's issue of Nature. Leonard Guarente, Shin-ichiro Imai, and their coworkers at MIT say the protein, which extends the life of yeast cells and has homologues in higher eukaryotes, is regulated by NAD, the ubiquitous coenzyme needed for oxidation/reduction reactions during food breakdown.

The researchers show that both yeast and mouse Sir2 proteins are histone deacetylases, and they offer evidence that in this capacity Sir2 participates in "silencing" transcription in overactive chromatin. This activity, in both yeast and mice nuclei, they show to be dependent on NAD. The authors speculate that when caloric intake is decreased, more NAD becomes available to Sir2, which can become more active in its deacetylation of histone proteins, resulting in the silencing of overactive transcription and the extension of cell life.

Regarding the relevance of this finding to Alzheimer's disease, Guarente points out that it depends on how one views Alzheimer's. "I'm not sure how direct a link there's going to be between Alzheimer's disease and aging. I think of aging as changes that would occur in all of the individuals in the population if they live long enough. Is Alzheimer's aging? I think it's debatable. I personally would say probably not; it's probably pathology."-Hakon Heimer.
References: Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000 Feb 17;403:795-800. Abstract

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  1. . Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. PubMed.

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  1. . Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. PubMed.

Primary Papers

  1. . Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795-800. PubMed.