Brian Kennedy

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. ncbi request reprint Genome-wide identification of conserved longevity genes in yeast and worms
    Erica D Smith
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mech Ageing Dev 128:106-11. 2007
  2. pmc Evidence that proteasome-dependent degradation of the retinoblastoma protein in cells lacking A-type lamins occurs independently of gankyrin and MDM2
    Ryan T Nitta
    Department of Biochemistry, University of Washington, Seattle, Washington, USA
    PLoS ONE 2:e963. 2007
  3. pmc Cell-extrinsic defective lymphocyte development in Lmna(-/-) mice
    J Scott Hale
    Department of Immunology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 5:e10127. 2010
  4. pmc Sir2-independent life span extension by calorie restriction in yeast
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    PLoS Biol 2:E296. 2004
  5. pmc Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans
    Erica D Smith
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
    BMC Dev Biol 8:49. 2008
  6. ncbi request reprint Mammalian transcription factors in yeast: strangers in a familiar land
    Brian K Kennedy
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Mol Cell Biol 3:41-9. 2002
  7. ncbi request reprint Ruminations on dietary restriction and aging
    B K Kennedy
    Department of Biochemistry, University of Washington, Seattle, WA 98195 7350, USA
    Cell Mol Life Sci 64:1323-8. 2007
  8. pmc Stabilization of the retinoblastoma protein by A-type nuclear lamins is required for INK4A-mediated cell cycle arrest
    Ryan T Nitta
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mol Cell Biol 26:5360-72. 2006
  9. pmc Hot topics in aging research: protein translation, 2009
    Brian K Kennedy
    Departments of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Aging Cell 8:617-23. 2009
  10. doi request reprint Translate this ... during dietary restriction
    Brian K Kennedy
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Cell Metab 10:247-8. 2009

Research Grants

  1. TOR, Translation and Aging
    Brian Kennedy; Fiscal Year: 2009
  2. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2009
  3. S6 Kinase, Aging and Age-related Disease
    Brian Kennedy; Fiscal Year: 2009
  4. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2009
  5. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2007
  6. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2007
  7. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2006
  8. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2006
  9. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2005
  10. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2004

Collaborators

Detail Information

Publications48

  1. ncbi request reprint Genome-wide identification of conserved longevity genes in yeast and worms
    Erica D Smith
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mech Ageing Dev 128:106-11. 2007
    ..Here we compare and contrast the results from genome-wide aging screens and assess the likelihood that there are "public" aging mechanisms...
  2. pmc Evidence that proteasome-dependent degradation of the retinoblastoma protein in cells lacking A-type lamins occurs independently of gankyrin and MDM2
    Ryan T Nitta
    Department of Biochemistry, University of Washington, Seattle, Washington, USA
    PLoS ONE 2:e963. 2007
    ..p14(arf) expression was also insufficient to stabilize pRB or confer cell cycle arrest, suggesting that MDM2 also does not mediate pRB degradation in Lmna-/- cells...
  3. pmc Cell-extrinsic defective lymphocyte development in Lmna(-/-) mice
    J Scott Hale
    Department of Immunology, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 5:e10127. 2010
    ..Lmna(-/-) mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development...
  4. pmc Sir2-independent life span extension by calorie restriction in yeast
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington, USA
    PLoS Biol 2:E296. 2004
    ..These findings indicate that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes...
  5. pmc Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans
    Erica D Smith
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
    BMC Dev Biol 8:49. 2008
    ..Dietary restriction (DR) increases life span and delays age-associated disease in many organisms. The mechanism by which DR enhances longevity is not well understood...
  6. ncbi request reprint Mammalian transcription factors in yeast: strangers in a familiar land
    Brian K Kennedy
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Mol Cell Biol 3:41-9. 2002
    ..Often, the mammalian factor retains function in yeast, and this allows investigators to exploit the experimental tractability of yeast to ask a diverse set of questions...
  7. ncbi request reprint Ruminations on dietary restriction and aging
    B K Kennedy
    Department of Biochemistry, University of Washington, Seattle, WA 98195 7350, USA
    Cell Mol Life Sci 64:1323-8. 2007
    ..Here we discuss the links between nutrient reduction and enhanced longevity with emphasis on evolutionarily conserved nutrient response signaling...
  8. pmc Stabilization of the retinoblastoma protein by A-type nuclear lamins is required for INK4A-mediated cell cycle arrest
    Ryan T Nitta
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mol Cell Biol 26:5360-72. 2006
    ..These findings do link lamin A/C to the functional activation of a critical tumor suppressor pathway and further the possibility that somatic mutations in LMNA contribute to tumor progression...
  9. pmc Hot topics in aging research: protein translation, 2009
    Brian K Kennedy
    Departments of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Aging Cell 8:617-23. 2009
    ..Other significant findings have connected translation control with other known longevity pathways and provided fodder for mechanistic hypotheses. Here, we summarize advances in this emerging field and raise questions for future studies...
  10. doi request reprint Translate this ... during dietary restriction
    Brian K Kennedy
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Cell Metab 10:247-8. 2009
    ..Recently, Zid et al. (Zid et al., 2009) linked the benefits of dietary restriction in flies to increased levels of the downstream TOR target 4E-BP1 and corresponding changes in the relative translation rates of classes of mRNAs...
  11. doi request reprint The genetics of ageing: insight from genome-wide approaches in invertebrate model organisms
    B K Kennedy
    Department of Biochemistry, University of Washington, Seattle, WA, USA
    J Intern Med 263:142-52. 2008
    ..In this review, I discuss data from genome-wide screens in the context of evolutionary theories of ageing and raise issues regarding the increasing complexity associated with the genetics of longevity...
  12. ncbi request reprint Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast
    Mitsuhiro Tsuchiya
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Aging Cell 5:505-14. 2006
    ..Thus, we propose that lifespan extension by CR is independent of sirtuins and that nicotinamide has sirtuin-independent effects on lifespan extension by CR...
  13. pmc Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4
    Kristan K Steffen
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Cell 133:292-302. 2008
    ..Genetic epistasis analyses suggest that dietary restriction, reduced 60S subunit abundance, and Gcn4 activation extend yeast life span by similar mechanisms...
  14. pmc Extension of chronological life span in yeast by decreased TOR pathway signaling
    R Wilson Powers
    Department of Genome Sciences and Medicine, The Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA
    Genes Dev 20:174-84. 2006
    ..We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes...
  15. ncbi request reprint Lifespan extension in Caenorhabditis elegans by complete removal of food
    Tammi L Kaeberlein
    Department of Microbiology, University of Washington, Seattle, WA, USA
    Aging Cell 5:487-94. 2006
    ..Removal of bacterial food also increases lifespan when initiated in postreproductive adults, suggesting that dietary restriction started during middle age can result in a substantial longevity benefit that is independent of reproduction...
  16. ncbi request reprint The enigmatic role of Sir2 in aging
    Brian K Kennedy
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Cell 123:548-50. 2005
    ..In contrast to measurements of aging for mitotic cells, cell survival in the nonmitotic state is decreased by Sir2 activity under conditions that mimic calorie restriction...
  17. ncbi request reprint Substrate-specific activation of sirtuins by resveratrol
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 280:17038-45. 2005
    ..In light of these findings, the mechanism accounting for putative longevity effects of resveratrol should be reexamined...
  18. pmc Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans
    Katherine A Steinkraus
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
    Aging Cell 7:394-404. 2008
    ..These findings demonstrate that dietary restriction confers a general protective effect against proteotoxicity and promotes longevity by a mechanism involving hsf-1...
  19. pmc Recent developments in yeast aging
    Matt Kaeberlein
    Department of Pathology, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 3:e84. 2007
    ..Here we briefly outline aging in yeast and describe recent findings that continue to keep this "simple" eukaryote at the forefront of aging research...
  20. pmc Quantitative evidence for conserved longevity pathways between divergent eukaryotic species
    Erica D Smith
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Genome Res 18:564-70. 2008
    ..Together, these findings indicate that the genetic component of life span determination is significantly conserved between divergent eukaryotic species, and suggest pathways that are likely to play a similar role in mammalian aging...
  21. ncbi request reprint Protein translation, 2007
    Matt Kaeberlein
    Department of Pathology, University of Washington, Seattle, WA 98195 7470, USA
    Aging Cell 6:731-4. 2007
    ..This Hot Topic article discusses papers published in the last year related to the importance of translation and its regulation by signaling through the target of rapamycin kinase, in modulating aging and age-associated diseases...
  22. doi request reprint Protein translation, 2008
    Matt Kaeberlein
    Department of Pathology, University of Washington, Seattle, WA 98195 7470, USA
    Aging Cell 7:777-82. 2008
    ..Importantly, studies published this year also began to provide insights into specific mechanisms by which altered mRNA translation does (and in some cases does not) slow aging in invertebrate model organisms...
  23. ncbi request reprint A method for high-throughput quantitative analysis of yeast chronological life span
    Christopher J Murakami
    Department of Pathology, University of Washington, Box 357470, Seattle, WA 98195 7470, USA
    J Gerontol A Biol Sci Med Sci 63:113-21. 2008
    ..We also report that life-span extension from dietary restriction does not require any of the five yeast sirtuins (Sir2, Hst1, Hst2, Hst3, or Hst4) either alone or in combination...
  24. pmc Increased life span due to calorie restriction in respiratory-deficient yeast
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 1:e69. 2005
    ....
  25. ncbi request reprint Comment on "HST2 mediates SIR2-independent life-span extension by calorie restriction"
    Matt Kaeberlein
    Department of Pathology, University of Washington, Seattle, WA 98195, USA
    Science 312:1312; author reply 1312. 2006
    ..Contradictory to this, we find that CR greatly increases life span in cells lacking Sir2, Hst1, and Hst2, which suggests that CR is not mediated by Sir2, Hst2, or Hst1...
  26. ncbi request reprint Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients
    Matt Kaeberlein
    Departments of Genome Sciences and Medicine, University of Washington, Seattle, WA 98195, USA
    Science 310:1193-6. 2005
    ..We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast...
  27. ncbi request reprint Large-scale identification in yeast of conserved ageing genes
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Mech Ageing Dev 126:17-21. 2005
    ....
  28. pmc A-type nuclear lamins act as transcriptional repressors when targeted to promoters
    Damian C Lee
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Exp Cell Res 315:996-1007. 2009
    ..These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter...
  29. ncbi request reprint Single-gene deletions that restore mating competence to diploid yeast
    Tom Schmidlin
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    FEMS Yeast Res 8:276-86. 2008
    ..In summary, this study underscores and elaborates upon predicted pathways by which mutations restore mating function to yeast diploids and identifies new mutants warranting further study...
  30. ncbi request reprint Genes determining yeast replicative life span in a long-lived genetic background
    Matt Kaeberlein
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Mech Ageing Dev 126:491-504. 2005
    ..These results define a limited number of genes likely to regulate replicative life span in a strain-independent manner, and create a basis for future epistasis analysis to determine genetic pathways of aging...
  31. pmc The TOR pathway comes of age
    Monique N Stanfel
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Biochim Biophys Acta 1790:1067-74. 2009
    ..Longevity studies in mammals are not published to date. Instead, we highlight studies in mouse models, which indicate that dampening the TOR pathway leads to widespread protection from an array of age-related diseases...
  32. ncbi request reprint Progeria syndromes and ageing: what is the connection?
    Christopher R Burtner
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Nat Rev Mol Cell Biol 11:567-78. 2010
    ..These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process...
  33. pmc The sensitivity of yeast mutants to oleic acid implicates the peroxisome and other processes in membrane function
    Daniel Lockshon
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    Genetics 175:77-91. 2007
    ..We propose that yeast deficient in peroxisomal and other functions are sensitive to oleate perhaps because of an inability to effectively control the fatty acid composition of membrane phospholipids...
  34. pmc Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation
    Richard L Frock
    Department of Biochemistry, Molecular and Cellular Biology Program, University of Washington, Seattle, Washington 98195, USA
    Genes Dev 20:486-500. 2006
    ..The delayed differentiation kinetics and decreased differentiation potential of lamin A/C-deficient and emerin-deficient myoblasts may in part underlie the dystrophic phenotypes observed in patients with EDMD...
  35. ncbi request reprint Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases
    Brian A Kudlow
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Nat Rev Mol Cell Biol 8:394-404. 2007
    ....
  36. pmc Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A
    Linda C Enns
    Department of Comparative Medicine, University of Washington, Seattle, WA, 98915, USA
    J Gerontol A Biol Sci Med Sci 64:1221-31. 2009
    ..These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance...
  37. ncbi request reprint A-type nuclear lamins, progerias and other degenerative disorders
    Erica D Smith
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mech Ageing Dev 126:447-60. 2005
    ..Here, we compare and contrast the LMNA mutations leading to laminopathies with emphasis on progerias, and discuss possible functional roles for A-type lamins in the maintenance of healthy tissues...
  38. pmc A molecular mechanism of chronological aging in yeast
    Christopher R Burtner
    Department of Biochemistry, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
    Cell Cycle 8:1256-70. 2009
    ..We conclude that acetic acid induced mortality is the primary mechanism of chronological aging in yeast under standard conditions...
  39. ncbi request reprint Aging: progeria and the lamin connection
    Brian A Kudlow
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Curr Biol 16:R652-4. 2006
    ..A recent study finds that LMNA, a gene targeted for mutation in Hutchinson Gilford Progeria Syndrome, may control the onset of aging-associated decline in normal fibroblasts...
  40. ncbi request reprint LMNA mutations in atypical Werner's syndrome
    Lishan Chen
    Department of Pathology, University of Washington, Seattle, WA 98195 7470, USA
    Lancet 362:440-5. 2003
    ..Some features of this disorder are also present in laminopathies caused by mutant LMNA encoding nuclear lamin A/C. Because of this similarity, we sequenced LMNA in individuals with atypical Werner's syndrome (wild-type WRN)...
  41. ncbi request reprint LMNA mutations in progeroid syndromes
    Shurong Huang
    Department of Pathology, University of Washington, Box 357470, Seattle, WA 98195, USA
    Novartis Found Symp 264:197-202; discussion 202-7, 227-30. 2005
    ..When compared to WRN-mutant WS, LMNA-mutant atypical WS patients appear to show earlier onset and possibly more severe ageing-related symptoms...
  42. ncbi request reprint HIV protease inhibitors block adipocyte differentiation independently of lamin A/C
    Brian A Kudlow
    Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA
    AIDS 19:1565-73. 2005
    ..To determine the importance of lamin A/C for fat cell differentiation in vitro and for the anti-adipogenic activity of HIV protease inhibitors such as indinavir...
  43. pmc Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53
    Brian A Kudlow
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Mol Biol Cell 19:5238-48. 2008
    ....
  44. ncbi request reprint Does resveratrol activate yeast Sir2 in vivo?
    Matt Kaeberlein
    Aging Cell 6:415-6. 2007
  45. pmc A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation
    Brett R Johnson
    Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 101:9677-82. 2004
    ..They further raise the possibility that altered pRB function may be a contributing factor in dystrophic syndromes arising from LMNA mutation...
  46. ncbi request reprint Sirtuins in aging and age-related disease
    Valter D Longo
    Department of Molecular and Computational Biology, Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089, USA
    Cell 126:257-68. 2006
    ..Here we examine the roles of Sirtuins in diverse eukaryotic species, with special emphasis on their links to aging and age-related diseases including cancer, diabetes, and neurodegenerative disorders...
  47. pmc Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit
    David A Barbie
    Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
    Mol Cell Biol 24:595-607. 2004
    ..These results suggest that mammalian cells undergo a large-scale reorganization of chromatin during the rounds of DNA replication that precede cell cycle exit...
  48. ncbi request reprint Nuclear tumor suppressors in space and time
    David A Barbie
    Department of Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Trends Cell Biol 15:378-85. 2005
    ..Here, we describe several recent studies that promote the view that regulated association with subcompartments of the nucleus is inherent to tumor-suppressor function...

Research Grants12

  1. TOR, Translation and Aging
    Brian Kennedy; Fiscal Year: 2009
    ..Through achieving a better understand of the modulatory role played by regulated protein translation in aging, we will be able to pinpoint key targets for pharmacological interventions. ..
  2. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2009
    ..Findings from these studies will identify and test potential mechanistic underpinnings that underlie Hutchinson-Gilford progeria syndrome and other A-type lamin-associated diseases. ..
  3. S6 Kinase, Aging and Age-related Disease
    Brian Kennedy; Fiscal Year: 2009
    ..We have determined that reduced S6 kinase function leads to lifespan extension in organisms ranging from yeast to mice. In this proposal, we will dissect the mechanisms by which S6 kinase activity accelerates the aging process. ..
  4. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2009
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  5. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2007
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..
  6. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2007
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  7. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2006
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..
  8. Genome-wide Analysis of Aging in Yeast
    Brian Kennedy; Fiscal Year: 2006
    ..When completed, this study will dramatically improve our understanding of aging in yeast and lead to models of caloric restriction that can be tested in mammalian systems. ..
  9. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2005
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..
  10. Nuclear Lamin Functions and Human Disease
    Brian Kennedy; Fiscal Year: 2004
    ..Myoblast cell lines, generated from Lmna-/- mice, exhibit differentiation defects. These defects will be studied at the molecular level to better understand how aberrant A-type lamin function leads to tissue degeneration. ..