Leonard P Guarente

Summary

Affiliation: Massachusetts Institute of Technology
Country: USA

Publications

  1. ncbi request reprint Calorie restriction--the SIR2 connection
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell 120:473-82. 2005
  2. ncbi request reprint Calorie restriction, SIRT1 and metabolism: understanding longevity
    Laura Bordone
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Mol Cell Biol 6:298-305. 2005
  3. ncbi request reprint Calorie restriction and SIR2 genes--towards a mechanism
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mech Ageing Dev 126:923-8. 2005
  4. ncbi request reprint A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span
    Mohan Viswanathan
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Dev Cell 9:605-15. 2005
  5. pmc Urea cycle regulation by mitochondrial sirtuin, SIRT5
    Takashi Nakagawa
    Paul F Glenn Laboratory for the Science of Aging and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Aging (Albany NY) 1:578-81. 2009
  6. pmc Sirtuin deacetylases in neurodegenerative diseases of aging
    Adrianna Z Herskovits
    Department of Pathology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Cell Res 23:746-58. 2013
  7. pmc SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production
    E L Bell
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    Oncogene 30:2986-96. 2011
  8. pmc SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin
    Petra Simic
    Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    EMBO Mol Med 5:430-40. 2013
  9. pmc Metabolic and neuropsychiatric effects of calorie restriction and sirtuins
    Sergiy Libert
    Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Physiol 75:669-84. 2013
  10. ncbi request reprint Sirtuins, aging, and metabolism
    Leonard Guarente
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Symp Quant Biol 76:81-90. 2011

Research Grants

  1. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2003
  2. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard P Guarente; Fiscal Year: 2010
  3. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2003
  4. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 2001
  5. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 2000
  6. Function of Mammalian SIRT1 in Aging
    Leonard Guarente; Fiscal Year: 2006
  7. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2006
  8. MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORS
    Leonard Guarente; Fiscal Year: 1999
  9. Function of Mammalian SIRT1 in Aging
    Leonard P Guarente; Fiscal Year: 2010
  10. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2002

Collaborators

Detail Information

Publications65

  1. ncbi request reprint Calorie restriction--the SIR2 connection
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cell 120:473-82. 2005
    ....
  2. ncbi request reprint Calorie restriction, SIRT1 and metabolism: understanding longevity
    Laura Bordone
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Mol Cell Biol 6:298-305. 2005
    ..In this review, we summarize recent findings that are beginning to clarify the mechanisms by which CR results in longevity and robust health, which might open new avenues of therapy for diseases of ageing...
  3. ncbi request reprint Calorie restriction and SIR2 genes--towards a mechanism
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mech Ageing Dev 126:923-8. 2005
    ..I then summarize what is known about the mammalian Sirt1 as it relates to physiological changes during CR, and discuss how this mechanism may impact on life span, as well as diseases of aging...
  4. ncbi request reprint A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span
    Mohan Viswanathan
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Dev Cell 9:605-15. 2005
    ..1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span...
  5. pmc Urea cycle regulation by mitochondrial sirtuin, SIRT5
    Takashi Nakagawa
    Paul F Glenn Laboratory for the Science of Aging and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Aging (Albany NY) 1:578-81. 2009
    ..Similar effects are also observed on high protein diet or calorie restriction. These data indicate SIRT5 also has an emerging role in the metabolic adaptation to fasting, high protein diet and calorie restriction...
  6. pmc Sirtuin deacetylases in neurodegenerative diseases of aging
    Adrianna Z Herskovits
    Department of Pathology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Cell Res 23:746-58. 2013
    ..Here, we describe sirtuin protein targets in several aggregate-forming neurodegenerative diseases and discuss the therapeutic potential of compounds that modulate sirtuin activity in these disorders...
  7. pmc SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production
    E L Bell
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    Oncogene 30:2986-96. 2011
    ..These data suggest that SirT3 acts to suppress the growth of tumors, at least in part through its ability to suppress ROS and HIF-1α...
  8. pmc SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin
    Petra Simic
    Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    EMBO Mol Med 5:430-40. 2013
    ..We conclude that SIRT1 deacetylates β-catenin to promote its accumulation in the nucleus leading to transcription of genes for MSC differentiation...
  9. pmc Metabolic and neuropsychiatric effects of calorie restriction and sirtuins
    Sergiy Libert
    Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Physiol 75:669-84. 2013
    ..We review the molecular understanding of CR; the role of sirtuins in CR; and the effects of sirtuins on physiology, mood, and behavior...
  10. ncbi request reprint Sirtuins, aging, and metabolism
    Leonard Guarente
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cold Spring Harb Symp Quant Biol 76:81-90. 2011
    ..Finally, I discuss emerging data showing protection by sirtuins against most of the common diseases of aging. It is possible that sirtuins will be novel targets to combat these diseases pharmacologically...
  11. pmc Mitochondria--a nexus for aging, calorie restriction, and sirtuins?
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA
    Cell 132:171-6. 2008
    ..In this Essay, I speculate on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow aging and associated diseases...
  12. ncbi request reprint Sirtuins as potential targets for metabolic syndrome
    Leonard Guarente
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 444:868-74. 2006
    ..Sirtuins and other important metabolic pathways that affect calorie restriction may serve as entry points for drugs to treat metabolic syndrome...
  13. doi request reprint Forever young
    Leonard Guarente
    Paul F Glenn Lab, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 140:176-8. 2010
    ..Liu et al. (2010) now describe a new mechanism of cell renewal in budding yeast, in which damaged protein aggregates are transported out of the daughter buds along actin cables to preserve youthfulness...
  14. ncbi request reprint Molecular mechanisms of yeast aging
    D A Sinclair
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Trends Biochem Sci 23:131-4. 1998
    ..However, recent discoveries might have validated one aging model in which the triggering of a molecular aging clock results in the replication and accumulation of a senescence factor that eventually overwhelms old cells...
  15. doi request reprint The logic linking protein acetylation and metabolism
    Leonard Guarente
    Paul F Glenn Laboratory, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell Metab 14:151-3. 2011
    ..A picture is presented in which protein acetylation is linked to available energy via the NAD-dependent deacetylases. This model suggests that protein acetylation regulates metabolic strategy and also helps store energy in cells...
  16. ncbi request reprint SIR2 and aging--the exception that proves the rule
    L Guarente
    Dept of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Trends Genet 17:391-2. 2001
    ..Here, I discuss a way of reconciling these two views that could have major implications for healthcare...
  17. ncbi request reprint Sir2 links chromatin silencing, metabolism, and aging
    L Guarente
    Department of Biology, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts 02139 USA
    Genes Dev 14:1021-6. 2000
  18. ncbi request reprint Diverse and dynamic functions of the Sir silencing complex
    L Guarente
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Genet 23:281-5. 1999
    ..I speculate that the Sir proteins may be capable of enzymatic modification of chromatin and other substrates, which enables them to carry out a broad range of cellular functions...
  19. ncbi request reprint Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration
    Su Ju Lin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 418:344-8. 2002
    ..We discuss how this metabolic strategy may apply to CR in animals...
  20. pmc Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction
    Dena E Cohen
    Paul F Glenn Laboratory, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 23:2812-7. 2009
    ..We conclude that Sirt1 in the brain is a link between somatotropic signaling and CR in mammals...
  21. ncbi request reprint SIR2: a potential target for calorie restriction mimetics
    Danica Chen
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Trends Mol Med 13:64-71. 2007
    ..The SIR2 family represents an evolutionarily conserved lifespan regulator. Modulating the activity of SIR2 might provide effective CR mimetics to combat diseases of aging...
  22. ncbi request reprint SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells
    Marcia C Haigis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
    Cell 126:941-54. 2006
    ..These results indicate that SIRT4 functions in beta cell mitochondria to repress the activity of GDH by ADP-ribosylation, thereby downregulating insulin secretion in response to amino acids, effects that are alleviated during CR...
  23. ncbi request reprint The Sir2 family of protein deacetylases
    Gil Blander
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Annu Rev Biochem 73:417-35. 2004
    ..We summarize the current knowledge of the Sir2 homologs from different organisms, and finally we discuss the role of Sir2 in caloric restriction and aging...
  24. ncbi request reprint Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction
    Marcia C Haigis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Genes Dev 20:2913-21. 2006
    ..The current findings sharpen our understanding of sirtuins as potential pharmacological targets to treat the major diseases of aging...
  25. pmc Mutations in Saccharomyces cerevisiae gene SIR2 can have differential effects on in vivo silencing phenotypes and in vitro histone deacetylation activity
    Christopher M Armstrong
    Department of Biology, Massachussetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Biol Cell 13:1427-38. 2002
    ..We also show that the histone deacetylase activity of Sir2p is necessary for the proper localiztion of the SIR complex to the telomeres...
  26. ncbi request reprint SIRT1 transgenic mice show phenotypes resembling calorie restriction
    Laura Bordone
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Aging Cell 6:759-67. 2007
    ..Our findings suggest that increased expression of SIRT1 in mice elicits beneficial phenotypes that may be relevant to human health and longevity...
  27. ncbi request reprint C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span
    Ala Berdichevsky
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Cell 125:1165-77. 2006
    ..We propose the existence of a stress-dependent pathway in which SIR-2.1 and 14-3-3 act in parallel to the insulin-like pathway to activate DAF-16 and extend life span...
  28. pmc Tissue-specific regulation of SIRT1 by calorie restriction
    Danica Chen
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 22:1753-7. 2008
    ..Our findings suggest that designing CR mimetics that target SIRT1 to provide uniform systemic benefits may be more complex than currently imagined...
  29. pmc The role of calorie restriction and SIRT1 in prion-mediated neurodegeneration
    Danica Chen
    Department of Biology, MIT, Cambridge, MA 02139, USA
    Exp Gerontol 43:1086-93. 2008
    ..Taken together, our results suggest a more complex interplay between CR, SIRT1, and neurodegenerative diseases than previously appreciated...
  30. pmc Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma
    Frederic Picard
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 429:771-6. 2004
    ..As a reduction in fat is sufficient to extend murine lifespan, our results provide a possible molecular pathway connecting calorie restriction to life extension in mammals...
  31. ncbi request reprint Two neurons mediate diet-restriction-induced longevity in C. elegans
    Nicholas A Bishop
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 447:545-9. 2007
    ....
  32. ncbi request reprint Mammalian SIRT1 represses forkhead transcription factors
    Maria Carla Motta
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 116:551-63. 2004
    ..We speculate how down-regulating these two classes of damage-responsive mammalian factors may favor long lifespan under certain environmental conditions, such as calorie restriction...
  33. ncbi request reprint Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease
    Su Ju Lin
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, MA 02139, USA
    Curr Opin Cell Biol 15:241-6. 2003
    ..Many human diseases are associated with changes in NAD level and/or the NAD : NADH ratio, raising the possibility that the Sir2p family might play a role in these diseases...
  34. ncbi request reprint How does calorie restriction work?
    Jana Koubova
    Department of Biology, MIT, Cambridge, Massachusetts 02139, USA
    Genes Dev 17:313-21. 2003
  35. ncbi request reprint Genetic links between diet and lifespan: shared mechanisms from yeast to humans
    Nicholas A Bishop
    Department of Biology, 77 Massachusetts Avenue, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Rev Genet 8:835-44. 2007
    ..Evidence is mounting that the brain has a crucial role in sensing dietary restriction and promoting longevity in metazoans...
  36. ncbi request reprint SIRT1 shows no substrate specificity in vitro
    Gil Blander
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 280:9780-5. 2005
    ..This result brings us one step closer to understanding how SIRT1 and possibly other protein deacetylases chose their substrate...
  37. ncbi request reprint Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase
    Gregory Liszt
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 280:21313-20. 2005
    ..These results provide the first characterization of a Sir2 protein from phylogenetic class IV...
  38. pmc Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells
    Laura Bordone
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 4:e31. 2006
    ..Sirt1 knockout mice display constitutively high UCP2 expression. Our findings show that Sirt1 regulates UCP2 in beta cells to affect insulin secretion...
  39. pmc Neurogenesis directed by Sirt1
    Sergiy Libert
    Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
    Nat Cell Biol 10:373-4. 2008
    ..These findings link a longevity gene to the activity of neuronal stem cells and their response to stress...
  40. ncbi request reprint SIRT1 deacetylates and positively regulates the nuclear receptor LXR
    Xiaoling Li
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Mol Cell 28:91-106. 2007
    ..Our findings suggest that deacetylation of LXRs by SIRT1 may be a mechanism that affects atherosclerosis and other aging-associated diseases...
  41. pmc Calorie restriction extends yeast life span by lowering the level of NADH
    Su Ju Lin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 18:12-6. 2004
    ..A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR...
  42. doi request reprint Aging and disease: connections to sirtuins
    Gizem Donmez
    Paul F Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Aging Cell 9:285-90. 2010
    ..Here we discuss several diseases of aging for which SIRT1 has been recently shown to confer protection. These findings suggest that manipulating sirtuin activity pharmacologically may be a fruitful area to improve human health...
  43. pmc SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
    Takashi Nakagawa
    Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Cell 137:560-70. 2009
    ..Similar effects occur during long-term calorie restriction or a high protein diet. These findings demonstrate SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating CPS1...
  44. pmc Acute oxidative stress can reverse insulin resistance by inactivation of cytoplasmic JNK
    Alina Berdichevsky
    Novartis Institute for Biomedical Research, Cardiovascular and Metabolism Disease Area, Cambridge, Massachusetts 02139, USA
    J Biol Chem 285:21581-9. 2010
    ..We propose that the contrasting effects of acute and chronic stress on insulin sensitivity are driven by changes in subcellular distribution of MKP7 and activated JNK...
  45. ncbi request reprint Increase in activity during calorie restriction requires Sirt1
    Danica Chen
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Science 310:1641. 2005
    ..In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice...
  46. pmc 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1
    Alina Berdichevsky
    Department of Biology, Paul F Glenn Laboratory, Howard Hughes Medical Institute, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 107:18927-32. 2010
    ..Our findings suggest that defects in fatty acid oxidation can limit lifespan and accelerate aging in C. elegans and that kat-1-mediated fatty acid oxidation is crucial for overexpressed sir-2.1 to delay aging...
  47. ncbi request reprint A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins
    Ala Berdichevsky
    Department of Biology, Massachusetts Insitute of Technology, Cambridge, Massachusetts 02139, USA
    Cell Cycle 5:2588-91. 2006
    ..In this prospective we review recent literature highlighting the role of SIR-2.1, 14-3-3 and other DAF-16 co-factors in DAF-16 activation...
  48. pmc Saccharomyces cerevisiae MPT5 and SSD1 function in parallel pathways to promote cell wall integrity
    Matt Kaeberlein
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genetics 160:83-95. 2002
    ..This work also provides evidence that post-transcriptional regulation is likely to be important both for maintaining cell integrity and for promoting longevity...
  49. pmc Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription
    Ethan Ford
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Genes Dev 20:1075-80. 2006
    ..Depletion of SIRT7 stops cell proliferation and triggers apoptosis. Our findings suggest that SIRT7 is a positive regulator of Pol I transcription and is required for cell viability in mammals...
  50. pmc SIRT1 promotes differentiation of normal human keratinocytes
    Gil Blander
    Genstruct Inc, One Alewife Center, Cambridge, Massachusetts 2140, USA
    J Invest Dermatol 129:41-9. 2009
    ..We conclude that SIRT1 functions in normal human keratinocytes to inhibit proliferation and to promote differentiation...
  51. ncbi request reprint Separation of mother and daughter cells
    Peter U Park
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Methods Enzymol 351:468-77. 2002
  52. ncbi request reprint Superoxide dismutase 1 knock-down induces senescence in human fibroblasts
    Gil Blander
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 278:38966-9. 2003
    ..Together, these findings support the notion that in normal human cells the SOD1 protein may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells...
  53. ncbi request reprint Model organisms as a guide to mammalian aging
    Heidi A Tissenbaum
    Program in Gene Function and Expression, University of Massachusetts Medical School, New Research Building Suite 604, 364 Plantation Street, Worcester, MA 01605, USA
    Dev Cell 2:9-19. 2002
    ..Here we review these findings with a focus on the nematode Caenorhabditis elegans and the budding yeast Saccharomyces cerevisiae and highlight general features of the regulation of aging that may have implications for mammals...
  54. pmc High osmolarity extends life span in Saccharomyces cerevisiae by a mechanism related to calorie restriction
    Matt Kaeberlein
    Longenity, Inc, Waltham, Massachusetts 02451, USA
    Mol Cell Biol 22:8056-66. 2002
    ..This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity...
  55. ncbi request reprint Life-span extension in yeast
    David A Sinclair
    Science 312:195-7; author reply 195-7. 2006
  56. ncbi request reprint Genetics and the specificity of the aging process
    Siegfried Hekimi
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Science 299:1351-4. 2003
    ..Thus, the aging process may be more specific than previously anticipated on evolutionary grounds...
  57. pmc Saccharomyces cerevisiae SSD1-V confers longevity by a Sir2p-independent mechanism
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Genetics 166:1661-72. 2004
    ..We propose that SSD1-V defines a previously undescribed pathway affecting cellular longevity and suggest that future studies on longevity-promoting genes should be carried out in long-lived SSD1-V strains...
  58. pmc Increased life span due to calorie restriction in respiratory-deficient yeast
    Su Ju Lin
    PLoS Genet 2:e33; author reply e34. 2006
  59. ncbi request reprint Scientific community. Aging research's family feud
    Jennifer Couzin
    Science 303:1276-9. 2004
  60. ncbi request reprint Genomic instability and aging-like phenotype in the absence of mammalian SIRT6
    Raul Mostoslavsky
    Howard Hughes Medical Institute, The Children s Hospital, CBR Institute for Biomedical Research, Harvard University Medical School, Boston, MA 02115, USA
    Cell 124:315-29. 2006
    ..We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes...
  61. ncbi request reprint NO link between calorie restriction and mitochondria
    Leonard Guarente
    Nat Chem Biol 1:355-6. 2005
  62. ncbi request reprint SIRT1 inhibits transforming growth factor beta-induced apoptosis in glomerular mesangial cells via Smad7 deacetylation
    Shinji Kume
    Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 520 2192, Japan
    J Biol Chem 282:151-8. 2007
    ..Our results suggest that up-regulation of SIRT1 deacetylase activity is a potentially useful therapeutic strategy for prevention of TGFbeta-related kidney disease through its effect on cell survival...
  63. pmc Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria
    Malcolm A Leissring
    Center for Neurologic Diseases, Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Biochem J 383:439-46. 2004
    ..Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria...
  64. pmc Science fact and the SENS agenda. What can we reasonably expect from ageing research?
    Huber Warner
    Buck Institute for Age Research, Novato, CA, USA
    EMBO Rep 6:1006-8. 2005
  65. pmc Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes
    Xiaobing Du
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Mol Cell Biol 24:8437-46. 2004
    ..These findings indicate that telomere dysfunction may contribute to the pathogenesis of Werner syndrome and Bloom syndrome...

Research Grants38

  1. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2003
    ..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
  2. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard P Guarente; Fiscal Year: 2010
    ..elegans that will identify new genes, mechanisms and pathways driving this process. Our findings may lead to new therapeutic approaches to diseases of aging in humans. ..
  3. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2003
    ..elegans. They also may shed light on a molecular mechanism of CR in an animal. These findings may have direct relevance to aging and the extension of life span by CR in mammals. ..
  4. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 2001
    ....
  5. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 2000
    ....
  6. Function of Mammalian SIRT1 in Aging
    Leonard Guarente; Fiscal Year: 2006
    ..This project will enable us to understand the regulation of aging in mammals by SIRTI. It may also have implications for diseases of aging, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease. ..
  7. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2006
    ..elegans. They also may shed light on a molecular mechanism of CR in an animal. These findings may have direct relevance to aging and the extension of life span by CR in mammals. ..
  8. MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORS
    Leonard Guarente; Fiscal Year: 1999
    ..Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically. ..
  9. Function of Mammalian SIRT1 in Aging
    Leonard P Guarente; Fiscal Year: 2010
    ..We plan to determine the functions of mammalian sirtuins, with emphasis on SIRT1, in multiple cell types in mice. These studies may suggest new strategies to treat diseases of aging. ..
  10. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2002
    ..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
  11. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2005
    ..elegans. They also may shed light on a molecular mechanism of CR in an animal. These findings may have direct relevance to aging and the extension of life span by CR in mammals. ..
  12. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2004
    ..elegans. They also may shed light on a molecular mechanism of CR in an animal. These findings may have direct relevance to aging and the extension of life span by CR in mammals. ..
  13. Function of Mammalian SIRT1 in Aging
    Leonard Guarente; Fiscal Year: 2004
    ..This project will enable us to understand the regulation of aging in mammals by SIRTI. It may also have implications for diseases of aging, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease. ..
  14. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 2007
    ..Importantly, CR is known to forestall orprevent many diseases of aging in rodent models. Therefore, drugs that are developed against targets we identify may open new strategies to treat diseases of aging. ..
  15. Function of Mammalian SIRT1 in Aging
    Leonard Guarente; Fiscal Year: 2007
    ..This project will enable us to understand the regulation of aging in mammals by SIRTI. It may also have implications for diseases of aging, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease. ..
  16. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2002
    ..elegans. They also may shed light on a molecular mechanism of CR in an animal. These findings may have direct relevance to aging and the extension of life span by CR in mammals. ..
  17. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 1999
    ..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
  18. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 1999
    ....
  19. CELL SENESCENCE IN SACCHAROMYCES CEREVISIAE
    Leonard Guarente; Fiscal Year: 1993
    ..The genes identified in these various genetic selections and screens will be cloned and sequenced. Functional relevance of these genes to aging, senescence, and cell death in higher organisms will be evaluated...
  20. MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORS
    Leonard Guarente; Fiscal Year: 2000
    ..Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically. ..
  21. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2001
    ..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
  22. MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORS
    Leonard Guarente; Fiscal Year: 2001
    ..Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically. ..
  23. MOLECULAR STUDY OF YEAST SGS1 AND RDNA CIRCLES IN AGING
    Leonard Guarente; Fiscal Year: 2000
    ..The overarching goal is to slow down aging in at least some organs to provide a higher quality of life as people enter their twilight years. ..
  24. Function of Mammalian SIRT1 in Aging
    Leonard Guarente; Fiscal Year: 2005
    ..This project will enable us to understand the regulation of aging in mammals by SIRTI. It may also have implications for diseases of aging, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disease. ..
  25. Molecular Study of sir-2 genes and Aging in C. elegans
    Leonard Guarente; Fiscal Year: 2009
    ..elegans that will identify new genes, mechanisms and pathways driving this process. Our findings may lead to new therapeutic approaches to diseases of aging in humans. ..