MIT hired Guarente and he opened his own lab in 1981; The Kenyon and Guarente labs came to lead the field studying the genetics of aging. In 1995 the Guarente lab identified the gene SIR4 (Silent information regulator 4) as a longevity regulator. When SIR4 was mutated in a single cell organism
S. cerevisiae longevity was extended. It was later determined that the complex of SIR2 and SIR4 are responsible for longevity phenotype, and that over-expression of SIR2 alone was sufficient to extend lifespan. Moreover, scientists in Guarente laboratory determined that SIR2 is necessary for longevity extension by calorie restriction. In 1999, Guarente and Kenyon became co-founders of Elixir Pharmaceuticals, which aimed to develop drugs targeting
sirtuin; Guarente made the case that involvement of SIR2 in metabolism and lifespan is conserved in other organisms. In round worm, Guarente reported that Caenorhabditis elegans, expression of SIR2 (sir2.1) is sufficient to extend longevity and in the fruit fly,
Drosophila melanogaster, overexpression of SIR2 was also reported to extended lifespan. However, other groups have disputed this finding and showed that SIR2-expression does not cause lifespan extension in worms or flies. Overexpression of SIRT1 (mammalian sir2 homolog) does not extend lifespan. Several of Guarente's high profile publications on SIRT1 have been retracted or corrected. Guarente wrote an autobiography in 2003 titled ''Ageless Quest: One Scientist's Search for Genes That Prolong Youth''. Guarente's rivalry with Sinclair, which began in 2002 when Sinclair challenged Guarante's description of how
sir2 might be involved in aging at a scientific meeting at Cold Spring Harbor Laboratory, was the subject of an article in
Science in 2004. In 2014 Guarente co-founded the
dietary supplement company
Elysium Health. == References ==