Leonard P. Guarente

Leonard P. Guarente

Novartis Professor of Biology

Leonard P. Guarente looks at mammal, mouse, and human brains to understand the genetic underpinning of aging and age-related diseases like Alzheimer’s.

617-253-6965

Phone

68-280

Office

leng@mit.edu

Email

Building 68 - Koch Biology Building

Location

Lab Website
Mary Gallagher

Assistant

617-258-7360

Assistant Phone

Education

  • PhD, 1978, Harvard University
  • SB, 1974, Biology, MIT

Research Summary

We combine comprehensive bioinformatics analyses with functional analyses of pathways and genes to study aging in humans and mice. We apply these approaches to identify the major pathways and genes involved in the aging of certain brain regions. We are also studying muscular dystrophy and muscle loss with aging. Ultimately, our findings may guide studies in other organs and lead to a systemic understanding of mammalian aging.

Awards

  • Miami Winter Symposium, Feodor Lynen Award, 2012
  • University of Toronto, Charles H. Best Lectureship and Award, 2011
  • Dart/NYU Biotechnology, Achievement Award, 2009
  • French Academie des Sciences, Elected, 2009
  • American Academy of Arts and Sciences, Fellow, 2004

Key Publications

  1. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Picard, F, Kurtev, M, Chung, N, Topark-Ngarm, A, Senawong, T, Machado De Oliveira, R, Leid, M, McBurney, MW, Guarente, L. 2004. Nature 429, 771-6.
    doi: 10.1038/nature02583PMID:15175761
  2. Mammalian SIRT1 represses forkhead transcription factors. Motta, MC, Divecha, N, Lemieux, M, Kamel, C, Chen, D, Gu, W, Bultsma, Y, McBurney, M, Guarente, L. 2004. Cell 116, 551-63.
    doi: 10.1016/s0092-8674(04)00126-6PMID:14980222
  3. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Tissenbaum, HA, Guarente, L. 2001. Nature 410, 227-30.
    doi: 10.1038/35065638PMID:11242085
  4. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Imai, S, Armstrong, CM, Kaeberlein, M, Guarente, L. 2000. Nature 403, 795-800.
    doi: 10.1038/35001622PMID:10693811
  5. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Kaeberlein, M, McVey, M, Guarente, L. 1999. Genes Dev 13, 2570-80.
    doi: 10.1101/gad.13.19.2570PMID:10521401

Recent Publications

  1. 4-Phenylbutyrate restores localization and membrane repair to human dysferlin mutations. Tominaga, K, Tominaga, N, Williams, EO, Rufibach, L, Schöwel, V, Spuler, S, Viswanathan, M, Guarente, LP. 2022. iScience 25, 103667.
    doi: 10.1016/j.isci.2021.103667PMID:35028538
  2. Rate of brain aging and APOE ε4 are synergistic risk factors for Alzheimer's disease. Glorioso, CA, Pfenning, AR, Lee, SS, Bennett, DA, Sibille, EL, Kellis, M, Guarente, LP. 2019. Life Sci Alliance 2, .
    doi: 10.26508/lsa.201900303PMID:31133613
  3. SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis. Herskovits, AZ, Hunter, TA, Maxwell, N, Pereira, K, Whittaker, CA, Valdez, G, Guarente, LP. 2018. Aging Cell 17, e12839.
    doi: 10.1111/acel.12839PMID:30295421
  4. It takes two to tango: NAD+ and sirtuins in aging/longevity control. Imai, SI, Guarente, L. 2016. NPJ Aging Mech Dis 2, 16017.
    doi: 10.1038/npjamd.2016.17PMID:28721271
  5. The brain, sirtuins, and ageing. Satoh, A, Imai, SI, Guarente, L. 2017. Nat Rev Neurosci 18, 362-374.
    doi: 10.1038/nrn.2017.42PMID:28515492
  6. Sirtuin 1 Promotes Deacetylation of Oct4 and Maintenance of Naive Pluripotency. Williams, EO, Taylor, AK, Bell, EL, Lim, R, Kim, DM, Guarente, L. 2016. Cell Rep 17, 809-820.
    doi: 10.1016/j.celrep.2016.09.046PMID:27732856
  7. CELL METABOLISM. The resurgence of NAD⁺. Guarente, L. 2016. Science 352, 1396-7.
    doi: 10.1126/science.aag1718PMID:27313027
  8. The multifaceted functions of sirtuins in cancer. Chalkiadaki, A, Guarente, L. 2015. Nat Rev Cancer 15, 608-24.
    doi: 10.1038/nrc3985PMID:26383140
  9. SirT1 is required in the male germ cell for differentiation and fecundity in mice. Bell, EL, Nagamori, I, Williams, EO, Del Rosario, AM, Bryson, BD, Watson, N, White, FM, Sassone-Corsi, P, Guarente, L. 2014. Development 141, 3495-504.
    doi: 10.1242/dev.110627PMID:25142464
  10. Muscle-specific SIRT1 gain-of-function increases slow-twitch fibers and ameliorates pathophysiology in a mouse model of duchenne muscular dystrophy. Chalkiadaki, A, Igarashi, M, Nasamu, AS, Knezevic, J, Guarente, L. 2014. PLoS Genet 10, e1004490.
    doi: 10.1371/journal.pgen.1004490PMID:25032964
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