Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute [Public domain] via Wikimedia CommonsThe protein called silent information regulator 2 (Sir2) was first discovered in budding yeast, Saccharomyces cerevisiae. It belongs to a highly conserved family of proteins christened sirtuins, which are found in almost all organisms and are involved in responses to stressors, such as heat and starvation. In 1999, Sir2 was reported to increase lifespan in yeast cells (Genes Dev. 13, 12570–2580). Then in 2001, scientists reported a link between overexpression of the gene sir-2 and longevity in the nematode Caenorhabditis elegans (Nature 410, 227–230). A few years later, a second group of researchers noted a similar association of Sir2 with longevity in Drosophila melanogaster fruit flies (Proc. Natl. Acad. Sci. USA 101, 15998–16003; 2004). Furthermore, it was suggested that activation of Sir2 could be the mechanism underlying the lifespan-lengthening effects of calorie restriction, a well-documented phenomenon in many organisms, including mammals. The gathering body of work focused a great deal of attention on sirtuins as the fabled ‘fountain of youth.’ Research groups began looking for evidence that sirtuins’ longevity effects extended to mammals, such as mice, and began looking for ways to activate sirtuins and, they hoped, extend lifespan. But trouble was brewing in sirtuin research, as contradictory and inconclusive results began to accumulate, and questions began to surface about the genetic background of the experimental animals and the controls used in the original experiments.
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