Leonard P. Guarente
|Leonard P. Guarente|
|Born||1952 (age 62–63)
|Alma mater||Harvard University|
|Thesis||Genetics of Transcription Termination (1979)|
Leonard Pershing Guarente (born 1952) is an American biologist best known for his research on life span extension in the budding yeast Saccharomyces cerevisiae, round worms (Caenorhabditis elegans), and mice. He is currently a Novartis Professor of Biology at the Massachusetts Institute of Technology.
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.
Sir2 is a member of the sirtuin family of enzymes. Guarente a 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 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.
Leonard Guarente wrote an autobiography in 2003 titled Ageless Quest: One Scientist's Search for Genes That Prolong Youth.
- Bolino, August C. (2012). Men of Massachusetts: Bay State Contributors to American Society. p. 426. ISBN 1475933762.
- Kennedy, B.K., et al. (1995). "Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae". Cell 80 (3): 485–96.
- Kaeberlein, M., M. McVey, and L. Guarente (1999). "The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms.". Genes Dev 13 (19): 2570–80.
- Lin, S.J., P.A. Defossez, and L. Guarente (2000). "Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae". Science 289 (5487): 2126–8.
- Imai, S., et al. (2000). "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase". Nature 403 (6771): 795–800.
- Tissenbaum, H.A. and L. Guarente (2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans". Nature 410 (6825)): 227–30.
- Rogina, B. and S.L. Helfand (2004). "Sir2 mediates longevity in the fly through a pathway related to calorie restriction". Proc Natl Acad Sci U S A 101 (45): 15998–6003.
- Bordone, L., et al. (2007). "SIRT1 transgenic mice show phenotypes resembling calorie restriction". Aging Cell 6 (6): 759–67.