Leonard Guarente
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Leonard Pershing Guarente (born 1952) is an American
biologist A biologist is a scientist who conducts research in biology. Biologists are interested in studying life on Earth, whether it is an individual Cell (biology), cell, a multicellular organism, or a Community (ecology), community of Biological inter ...
best known for his research on life span extension in the budding yeast ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...
'', roundworms (''
Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
''), and mice. He is a Novartis Professor of Biology at the
Massachusetts Institute of Technology The Massachusetts Institute of Technology (MIT) is a Private university, private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of moder ...
.


Early life and education

Leonard Guarente was born and raised in
Revere, Massachusetts Revere (, ) is a city in Suffolk County, Massachusetts. Located approximately northeast of Downtown Boston, Revere is the terminus of the Blue Line (MBTA), MBTA Blue Line, with three stations located within the city: Wonderland station, Wonderla ...
and was the first person in his family to attend college, when he started his undergraduate work at MIT in 1970. He earned his Ph.D. at MIT, studying under
Jon Beckwith Jonathan Roger Beckwith (born December 25, 1935, in Cambridge, Massachusetts) is an American microbiologist and geneticist. He is the American Cancer Society Professor in the Department of Microbiology and Immunobiology at Harvard Medical School ...
and
Mark Ptashne Mark Ptashne (born June 5, 1940, in Chicago) is a molecular biologist. He is the Ludwig Chair of Molecular Biology at Memorial Sloan–Kettering Cancer Center in New York City. Ptashne grew up in Chicago. He earned his undergraduate degree at R ...
. He did a post doc at Harvard.


Science

MIT hired Guarente and he opened his own lab in 1981; he earned tenure there in 1986. For the first nine years, his lab studied
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...
in yeast. In 1991 his lab started to study 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. 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 Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins ...
; Guarente left the company seven years later after he disagreed with
venture capitalist Venture capital (VC) is a form of private equity financing provided by firms or funds to startup, early-stage, and emerging companies, that have been deemed to have high growth potential or that have demonstrated high growth in terms of number ...
s who had gained control of the company about the focus of the company. In 2000 the Guarente laboratory published work identifying SIR2's activity as a
NAD+ Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an ade ...
-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. 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 ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
'', 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 A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...
company Elysium Health.


References


External links


Guarente Lab
{{DEFAULTSORT:Guarente, P. Leonard 1952 births 21st-century American biologists Living people Harvard University alumni Life extensionists