Science
Sir2 is the founding member of the Sirtuin family of enzymes. Prof. Guarente is recognized as the leading proponent of the hypothesis that caloric restriction slows aging by activation of Sirtuins.
Initial discovery that happened in 1995 identified gene SIR4 (Silent information regulator 4) as a longevity regulator. When SIRT4 was mutated in a single cell organism Saccharomyces 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 ].
Imai Shin, a postdoctoral fellow in the laboratory of Leonard Guarente determined that SIR2 was an enzyme. It was NAD+-dependent protein de-acetylase ]. This NAD dependence explained how SIR2 could connect diet to physiology and suggested the mechanism, by which Calorie Restriction (CR) could extend lifespan.
The involvement of SIR2 in the metabolism and lifespan determination appeared to be conserved in other organisms. In round worm, Caenorhabditis elegans, expression of SIR2 (sir2.1) is sufficient to extend longevity ]. In fruit fly, Drosophila melanogaster, overexpression of sir2 also extended lifespan ]. Overexpression of SIRT1 (mammalian sir2 homolog) in mice improved their health and retarded numerous age-associated diseases ].
Leonard Guarente has written an autobiography titled "Ageless Quest: One Scientist's Search for Genes That Prolong Youth". The book was published in 2003 by Cold Spring Harbor Press.
Over the last decade, it was unambiguously shown that sirtuins regulate aging processes and play an important role in diseases of aging in mammals in general and in humans in particular. Some of the peer-reviewed publications on this subject are collected here (http://web.mit.edu/biology/guarente/publications/).
Read more about this topic: Leonard P. Guarente
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