Name Leonard Guarente | Role Biologist | |
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Thesis Genetics of Transcription Termination (1979) Education | ||
The past and the next ten years of sirtuin research drs shin ichiro imai leonard p guarente
Leonard Pershing Guarente (born 1952) is an American biologist best known for his research on life span extension in the budding yeast Saccharomyces cerevisiae, roundworms (Caenorhabditis elegans), and mice. He is a Novartis Professor of Biology at the Massachusetts Institute of Technology.
Contents
- The past and the next ten years of sirtuin research drs shin ichiro imai leonard p guarente
- 2016 roy walford lecture nad sirtuins and aging leonard p guarente phd
- Science
- References
Based on the discovery that SIR2 is a key regulator of longevity in both yeast and worms, he is interested in determining whether this highly conserved gene also governs longevity in other organisms, including mammals.
2016 roy walford lecture nad sirtuins and aging leonard p guarente phd
Science
Guarente's lab has studied the function of genes involved in aging. In 1993, Cynthia Kenyon's lab at UCSF discovered that a single-gene mutation in (Daf-2) could double the lifespan of C. elegans. That same year, David Sinclair joined the Guarente lab, and they developed the hypothesis that caloric restriction slows aging by activation of sirtuins.
In 1995 the lab identified the gene SIR4 (Silent information regulator 4) as a longevity regulator. When SIRT4 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.
The Guarente laboratory determined that SIR2 was an enzyme. It was NAD+-dependent protein deacetylase. This NAD dependence explained how SIR2 could connect diet to physiology and suggested the mechanism by which calorie restriction could extend the lifespan of some organisms.
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 the 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.
In 1999, Guarente and Kenyon became co-founders of Elixir Pharmaceuticals, which aimed to develop drugs targeting sirtuin; Guarente left the company seven years later after he disagreed with venture capitalists who had gained control of the company about the focus of the company.
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 he co-founded the dietary supplement company Elysium Health.