| RESEARCH |
biology professor at Massachusetts Institute of Technology, backs an alternate premise based on experiments involving yeast (Saccharomyces cerevisiae). Life span in yeast is equated with the number of times a mother cell can bud off a smaller daughter cell--typically an average of some 20 divisions and a maximum of about 40 divisions for normal, or wild-type, yeast. Guarente and his colleagues have found that growing yeast on media containing 0.5% glucose instead of the normal 2% increases life span by about 25%. They have determined that the effect is related to the SIR2 gene. The gene codes for Sir2 proteins, which deacetylate the lysine groups of histones as well as many other proteins. Histones are components of chromatin, the tightly bundled complexes of DNA, RNA, and protein that make up chromosomes. When Sir2 deacetylates histones, it compresses the structure of chromatin, silencing various stretches of DNA by making the regions less accessible for gene transcription. One benefit for yeast is a reduction in the production of DNA fragments during cell division--structures that cause aging. Sir2 acts in concert with nicotinamide adenine dinucleotide (NAD). Yeast cells produce NAD from its reduced form, NADH, through respiration. According to the researchers, calorie restriction tips the yeast's metabolism of glucose from fermentation to respiration. Therefore, Guarente and colleagues suggest that calorie restriction drives the conversion of NADH to NAD, lowering the NADH concentration and boosting the NAD:NADH ratio [Genes Dev., 18, 12 (2004)]. Because NADH is a Sir2 inhibitor, they reason, its reduction increases Sir2 activity. |
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