Siegfried Hekimi

Summary

Affiliation: McGill University
Country: Canada

Publications

  1. pmc Mitochondrial oxidative stress alters a pathway in Caenorhabditis elegans strongly resembling that of bile acid biosynthesis and secretion in vertebrates
    Ju Ling Liu
    Department of Biology, McGill University, Montreal, Canada
    PLoS Genet 8:e1002553. 2012
  2. pmc Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans
    Jeremy M Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec, Canada
    PLoS Genet 5:e1000361. 2009
  3. pmc A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans
    Wen Yang
    Department of Biology, McGill University, Montreal, Quebec, Canada
    PLoS Biol 8:e1000556. 2010
  4. pmc A mild impairment of mitochondrial electron transport has sex-specific effects on lifespan and aging in mice
    Bryan G Hughes
    Department of Biology, McGill University, Montreal, Canada
    PLoS ONE 6:e26116. 2011
  5. pmc The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/- mice
    Jerome Lapointe
    Department of Biology, McGill University, Montreal, Canada
    J Cell Biol 199:215-24. 2012
  6. ncbi request reprint Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity
    S Hekimi
    Dept of Biology, McGill University, 1205 Dr Penfield Avenue, Quebec, H3A 1B1, Montreal, Canada
    Trends Genet 17:712-8. 2001
  7. ncbi request reprint How genetic analysis tests theories of animal aging
    Siegfried Hekimi
    Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Quebec H3A 1B1, Canada
    Nat Genet 38:985-91. 2006
  8. ncbi request reprint Taking a "good" look at free radicals in the aging process
    Siegfried Hekimi
    Department of Biology, McGill University, Montreal, Canada H3A 1B1
    Trends Cell Biol 21:569-76. 2011
  9. 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
  10. pmc Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage
    Jeremy Michael Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 185:559-71. 2010

Collaborators

Detail Information

Publications60

  1. pmc Mitochondrial oxidative stress alters a pathway in Caenorhabditis elegans strongly resembling that of bile acid biosynthesis and secretion in vertebrates
    Ju Ling Liu
    Department of Biology, McGill University, Montreal, Canada
    PLoS Genet 8:e1002553. 2012
    ....
  2. pmc Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans
    Jeremy M Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec, Canada
    PLoS Genet 5:e1000361. 2009
    ..Overall, we show that increased oxidative stress caused by deletion of sod genes does not result in decreased lifespan in C. elegans and that deletion of sod-2 extends worm lifespan by altering mitochondrial function...
  3. pmc A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans
    Wen Yang
    Department of Biology, McGill University, Montreal, Quebec, Canada
    PLoS Biol 8:e1000556. 2010
    ..This model provides a new explanation for the well-documented correlation between ROS and the aged phenotype as a gradual increase of molecular damage during aging would trigger a gradually stronger ROS response...
  4. pmc A mild impairment of mitochondrial electron transport has sex-specific effects on lifespan and aging in mice
    Bryan G Hughes
    Department of Biology, McGill University, Montreal, Canada
    PLoS ONE 6:e26116. 2011
    ..These results demonstrate that even relatively small perturbations of the mitochondrial electron transport chain can have significant physiological effects in mammals, and that the severity of those effects can be sex-dependent...
  5. pmc The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/- mice
    Jerome Lapointe
    Department of Biology, McGill University, Montreal, Canada
    J Cell Biol 199:215-24. 2012
    ..These findings indicate that MCLK1 regulates both UQ synthesis and distribution within mitochondrial membranes...
  6. ncbi request reprint Genetics of lifespan in C. elegans: molecular diversity, physiological complexity, mechanistic simplicity
    S Hekimi
    Dept of Biology, McGill University, 1205 Dr Penfield Avenue, Quebec, H3A 1B1, Montreal, Canada
    Trends Genet 17:712-8. 2001
    ..Genetic analysis, however, suggests that these activities all converge on a few key mechanisms that impinge on lifespan, namely the production, repair and prevention of molecular damage...
  7. ncbi request reprint How genetic analysis tests theories of animal aging
    Siegfried Hekimi
    Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Quebec H3A 1B1, Canada
    Nat Genet 38:985-91. 2006
    ..Here, I analyze some of what we know today and discuss what we should try to find out in the future to understand the aging phenomenon...
  8. ncbi request reprint Taking a "good" look at free radicals in the aging process
    Siegfried Hekimi
    Department of Biology, McGill University, Montreal, Canada H3A 1B1
    Trends Cell Biol 21:569-76. 2011
    ..This could generate the observed correlation between aging and ROS without implying that ROS damage is the earliest trigger or main cause of aging...
  9. 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...
  10. pmc Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage
    Jeremy Michael Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 185:559-71. 2010
    ..Overall, our findings suggest that decreased energy metabolism can lead to increased life span without decreased production of ROS...
  11. pmc Reversal of the mitochondrial phenotype and slow development of oxidative biomarkers of aging in long-lived Mclk1+/- mice
    Jerome Lapointe
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 284:20364-74. 2009
    ....
  12. doi request reprint The anti-neurodegeneration drug clioquinol inhibits the aging-associated protein CLK-1
    Ying Wang
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 284:314-23. 2009
    ..Our findings support the hypothesis that pharmacologically targeting aging-associated proteins could help relieve age-dependent diseases...
  13. pmc Mitochondrial respiration without ubiquinone biosynthesis
    Ying Wang
    Department of Biology, McGill University, Montreal, Quebec, Canada H3A 1B1
    Hum Mol Genet 22:4768-83. 2013
    ..With this model, we also showed that diet-derived UQ10 is able to functionally rescue the electron transport deficit due to severe endogenous UQ deficiency in the liver, an organ capable of absorbing exogenous UQ...
  14. pmc Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice
    Xingxing Liu
    Department of Biology, McGill University, H3A 1B1, Montreal, Quebec, Canada
    Genes Dev 19:2424-34. 2005
    ..These observations indicate that the distinct mechanism by which clk-1/mclk1 affects lifespan is evolutionarily conserved from nematodes to mammals and is not tied to a particular anatomy or physiology...
  15. ncbi request reprint mau-2 acts cell-autonomously to guide axonal migrations in Caenorhabditis elegans
    Claire Y Benard
    Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec H3A 1B1, Canada
    Development 131:5947-58. 2004
    ..Taken together, mau-2 defines a novel guidance factor that might be involved in the intracellular processing of guidance cues encountered by migrating cells and axons during development...
  16. ncbi request reprint Lifelong protection from global cerebral ischemia and reperfusion in long-lived Mclk1(+/)(-) mutants
    Huaien Zheng
    Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Canada H3A 1B1
    Exp Neurol 223:557-65. 2010
    ....
  17. pmc Early mitochondrial dysfunction in long-lived Mclk1+/- mice
    Jerome Lapointe
    Department of Biology, McGill University, Montreal H3A 1B1, Canada
    J Biol Chem 283:26217-27. 2008
    ..Our model helps to clarify the relationship between energy metabolism and the aging process and suggests the need for a reformulation of the mitochondrial oxidative stress theory of aging...
  18. ncbi request reprint Genetic and molecular characterization of CLK-1/mCLK1, a conserved determinant of the rate of aging
    Zaruhi Stepanyan
    Department of Biology, McGill University, Montreal, Que, Canada
    Exp Gerontol 41:940-51. 2006
    ..The clk-1/mclk1 system could allow for the understanding of this mechanism by combining genetic and molecular investigations in worms with studies in mice, where age-dependent disease processes relevant to human health can be modeled...
  19. pmc Uncoupling the pleiotropic phenotypes of clk-1 with tRNA missense suppressors in Caenorhabditis elegans
    Robyn Branicky
    Department of Biology, McGill University, 1205 Ave Docteur Penfield, Montreal, Quebec, Canada H3A 1B1
    Mol Cell Biol 26:3976-85. 2006
    ..The pattern of suppression we observe suggests that the individual members of the tRNA(Glu) family are expressed in different tissues and at different levels...
  20. pmc Mclk1+/- mice are not resistant to the development of atherosclerosis
    Bryan G Hughes
    Department of Biology, McGill University, Montreal H3A 1B1, Canada
    Lipids Health Dis 8:16. 2009
    ..We sought to determine if Mclk1 heterozygosity protects against atherosclerosis and dyslipidemia in these models...
  21. pmc An enhanced immune response of Mclk1⁺/⁻ mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging
    Dantong Wang
    Department of Biology, McGill University, Montreal, Canada
    PLoS ONE 7:e49606. 2012
    ..This suggests that the immune phenotype of these mutants might contribute to their longevity. We discuss how these findings suggest a broader view of how the immune response might impact the aging process...
  22. doi request reprint Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans
    Wen Yang
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Aging Cell 9:433-47. 2010
    ..Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently...
  23. pmc A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans
    Wen Yang
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 177:2063-74. 2007
    ..We discuss the significance of our findings in light of the oxidative stress theory of aging...
  24. ncbi request reprint Molecular mechanism of maternal rescue in the clk-1 mutants of Caenorhabditis elegans
    Jason Burgess
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 278:49555-62. 2003
    ....
  25. ncbi request reprint Evolutionary conservation of drug action on lipoprotein metabolism-related targets
    Abdelmadjid K Hihi
    Chronogen, Inc, Montreal, Quebec, Canada
    J Lipid Res 49:74-83. 2008
    ..Thus, target processes for pharmacological intervention on lipoprotein synthesis, transport, and metabolism are conserved between nematodes and vertebrates, which allows the use of C. elegans for drug discovery...
  26. pmc Superoxide dismutase is dispensable for normal animal lifespan
    Jeremy Michael Van Raamsdonk
    Department of Biology, McGill University, Montreal, QC, Canada H3A 1B1
    Proc Natl Acad Sci U S A 109:5785-90. 2012
    ..Moreover, our findings indicate that maintaining normal stress resistance is not crucial to the rate of aging...
  27. ncbi request reprint When a theory of aging ages badly
    Jerome Lapointe
    Department of Biology, McGill University, Montreal H3A 1B1, Canada
    Cell Mol Life Sci 67:1-8. 2010
    ..Thus, we believe that it is reasonable to now consider the MFRTA as refuted and that it is time to use the insight gained by many years of testing this theory to develop new views as to the physiological causes of aging...
  28. ncbi request reprint Redox regulation of germline and vulval development in Caenorhabditis elegans
    Yukimasa Shibata
    Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Quebec, Canada, H3A 1B1
    Science 302:1779-82. 2003
    ..The other pathway is the oncogenic ras signaling pathway, whose action on germline as well as vulval development appears to be modulated by cytoplasmic ROS...
  29. ncbi request reprint Sensitivity of Caenorhabditis elegans clk-1 mutants to ubiquinone side-chain length reveals multiple ubiquinone-dependent processes
    Abdelmadjid K Hihi
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 278:41013-8. 2003
    ..This allows us to propose a model where we distinguish several types of Q-dependent processes in vivo: processes that are very sensitive to Q side-chain length and processes that are permissive to Q with shorter chains...
  30. ncbi request reprint Elevated mitochondrial reactive oxygen species generation affects the immune response via hypoxia-inducible factor-1alpha in long-lived Mclk1+/- mouse mutants
    Dantong Wang
    Department of Biology, McGill University, Montreal, Quebec, Canada
    J Immunol 184:582-90. 2010
    ..Our results further suggest that altered immune function through a limited increase in HIF-1alpha expression can positively impact animal longevity...
  31. ncbi request reprint Specification of muscle neurotransmitter sensitivity by a Paired-like homeodomain protein in Caenorhabditis elegans
    Robyn Branicky
    Department of Biology, McGill University, 1205 Avenue Dr Penfield, Montreal, Quebec H3A 1B1, Canada
    Development 132:4999-5009. 2005
    ..In addition, dsc-1, but not exp-1, affects the periodicity of the behavior, revealing an unanticipated role for the enteric muscles in regulating this ultradian rhythm...
  32. doi request reprint Lipid transport and signaling in Caenorhabditis elegans
    Robyn Branicky
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Dev Dyn 239:1365-77. 2010
    ....
  33. pmc Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans
    Liesbeth de Jong
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 168:845-54. 2004
    ....
  34. ncbi request reprint Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans
    J Feng
    Department of Biology, McGill University, 1205 Avenue Dr Penfield, H3A 1B1, , , Canada
    Dev Cell 1:633-44. 2001
    ..These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way...
  35. ncbi request reprint Ubiquinone is necessary for Caenorhabditis elegans development at mitochondrial and non-mitochondrial sites
    Abdelmadjid K Hihi
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 277:2202-6. 2002
    ..These results indicate that UQ is required for nematode development at mitochondrial and non-mitochondrial sites and that DMQ cannot functionally replace UQ at those non-mitochondrial sites...
  36. ncbi request reprint FUdR causes a twofold increase in the lifespan of the mitochondrial mutant gas-1
    Jeremy Michael Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec, Canada H2X 3H5
    Mech Ageing Dev 132:519-21. 2011
    ..Thus, the concentration of FUdR employed in a lifespan study can determine whether a particular strain is long-lived or short-lived compared to wild-type...
  37. ncbi request reprint Long-lived mutants, the rate of aging, telomeres and the germline in Caenorhabditis elegans
    Claire Bénard
    Department of Biology, McGill University, 1205 Avenue Dr Penfield, Quebec, Montreal, Canada
    Mech Ageing Dev 123:869-80. 2002
  38. ncbi request reprint Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1
    J J Ewbank
    Department of Biology, McGill University, 1205 Avenue Docteur Penfield, Montreal, Quebec, Canada H3A 1B1
    Science 275:980-3. 1997
    ..clk-1 complemented the phenotype of cat5/coq7 null mutants, demonstrating that clk-1 and CAT5/COQ7 share biochemical function and that clk-1 acts at the level of cellular physiology...
  39. pmc Viable maternal-effect mutations that affect the development of the nematode Caenorhabditis elegans
    S Hekimi
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Genetics 141:1351-64. 1995
    ..We present a partial phenotypic characterization of the mutants and a quantitative analysis of the degree to which they can be maternally or zygotically rescued...
  40. ncbi request reprint Molecular genetics of life span in C. elegans: how much does it teach us?
    S Hekimi
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Trends Genet 14:14-20. 1998
    ..The implications of these findings for our understanding of organismal ageing are discussed...
  41. ncbi request reprint Why only time will tell
    S Hekimi
    Department of Biology, McGill University, 1205 Avenue Dr Penfield, Quebec, H3A 1B1, Montreal, Canada
    Mech Ageing Dev 122:571-94. 2001
    ....
  42. ncbi request reprint Assessing the function of the Ro ribonucleoprotein complex using Caenorhabditis elegans as a biological tool
    J C Labbe
    Universite de Montreal, Departement de Biochimie, QC, Canada
    Biochem Cell Biol 77:349-54. 1999
    ..Here, we review the phenotypic analysis of C. elegans rop-l(-) mutants and integrate these results into a model for the function of the Ro RNP particle...
  43. ncbi request reprint Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation
    Ning Jiang
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    J Biol Chem 278:21678-84. 2003
    ..Surprisingly, we find that hCLK2 is present in all cellular compartments and exists as a membrane-associated as well as a soluble form...
  44. ncbi request reprint Molecular genetics of ubiquinone biosynthesis in animals
    Ying Wang
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Crit Rev Biochem Mol Biol 48:69-88. 2013
    ..Moreover, we review the phenotypes of mutants in these genes and discuss the functional consequences of UQ deficiency in general...
  45. ncbi request reprint What keeps C. elegans regular: the genetics of defecation
    Robyn Branicky
    Department of Biology, McGill University, 1205 Docteur Penfield Avenue, Montreal, Quebec H3A 1B1, Canada
    Trends Genet 22:571-9. 2006
    ..Our review highlights how the function of a system even this simple results from the integration of many aspects of an organism's biology and involves the action of diverse genes...
  46. doi request reprint Reactive Oxygen Species and Aging in Caenorhabditis elegans: Causal or Casual Relationship?
    Jeremy Michael Van Raamsdonk
    Department of Biology, McGill University, Montreal, Quebec, Canada
    Antioxid Redox Signal 13:1911-53. 2010
    ..Overall, the data in C. elegans indicate that oxidative damage can be dissociated from aging in experimental situations...
  47. ncbi request reprint Mouse CLK-1 is imported into mitochondria by an unusual process that requires a leader sequence but no membrane potential
    N Jiang
    Department of Biology, McGill University, H3A 1B1, , , Canada
    J Biol Chem 276:29218-25. 2001
    ..However, in contrast to all known mitochondrial proteins that contain a cleavable pre-sequence, the import of mCLK1 does not require a mitochondrial membrane potential...
  48. pmc Phenotypic and suppressor analysis of defecation in clk-1 mutants reveals that reaction to changes in temperature is an active process in Caenorhabditis elegans
    R Branicky
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 159:997-1006. 2001
    ..On the other hand, in the absence of clk-1 activity, we observe temperature compensation, a mechanism that maintains a constant defecation period in the face of changes in temperature...
  49. pmc The genetics of caloric restriction in Caenorhabditis elegans
    B Lakowski
    Department of Biology, McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1
    Proc Natl Acad Sci U S A 95:13091-6. 1998
    ..In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes...
  50. ncbi request reprint Cellular and axonal migrations are misguided along both body axes in the maternal-effect mau-2 mutants of Caenorhabditis elegans
    S Takagi
    Department of Biology, McGill University, Montreal, Canada
    Development 124:5115-26. 1997
    ..The possibility that mau-2 is involved in the spatial organization of guidance cues encoded by other genes is discussed...
  51. ncbi request reprint The Caenorhabditis elegans avermectin resistance and anesthetic response gene unc-9 encodes a member of a protein family implicated in electrical coupling of excitable cells
    T M Barnes
    Department of Biology, McGill University, Montreal, Quebec, Canada
    J Neurochem 69:2251-60. 1997
    ..Finally, we speculate on the basis of the avermectin resistance and anesthetic response phenotypes...
  52. ncbi request reprint The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length
    C Benard
    Department of Biology, McGill University, 1205 Avenue Dr Penfield, H3A 1B1, Montreal, Quebec, Canada
    Development 128:4045-55. 2001
    ..However, we find that a functional CLK-2::GFP fusion protein is cytoplasmic in worms. We discuss how the phenotype of clk-2 mutants could be the result of altered patterns of gene expression...
  53. pmc Regulation of physiological rates in Caenorhabditis elegans by a tRNA-modifying enzyme in the mitochondria
    J Lemieux
    Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada
    Genetics 159:147-57. 2001
    ..As oxygen consumption and ATP concentration have been reported to be unaffected in gro-1 mutants, our observations suggest that GRO-1 acts in mitochondria and regulates global physiology by unknown mechanisms...
  54. ncbi request reprint The intrinsic apoptosis pathway mediates the pro-longevity response to mitochondrial ROS in C. elegans
    Callista Yee
    Department of Biology, McGill University, Montreal, QC H3A 1B1, Canada
    Cell 157:897-909. 2014
    ..This results in extended longevity when mtROS generation is inappropriately elevated. These findings clarify the relationships between mitochondria, ROS, apoptosis, and aging...
  55. doi request reprint Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival
    Francis Robert
    Department of Biochemistry, McGill University, Montreal, Quebec, Canada
    Cancer Res 72:747-56. 2012
    ..Together, our findings suggest a new paradigm to treat ACS by strategies which target protein synthesis to block the production of procachexic factors...
  56. ncbi request reprint Quinones in long-lived clk-1 mutants of Caenorhabditis elegans
    Hiroko Miyadera
    Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, 113 0033, Tokyo, Japan
    FEBS Lett 512:33-7. 2002
    ..Here we elucidate the possible mechanisms of life span extension in clk-1 mutants, with particular emphasis on the electrochemical property of DMQ. Recent findings on the biochemical function of CLK-1 are also discussed...
  57. pmc Metazoan Scc4 homologs link sister chromatid cohesion to cell and axon migration guidance
    Vlad C Seitan
    Institute of Human Genetics, University of Newcastle, Newcastle upon Tyne, United Kingdom
    PLoS Biol 4:e242. 2006
    ....