longevity

Summary

Top Publications

  1. ncbi How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)
    Michael Ristow
    Dept of Human Nutrition, Institute of Nutrition, University of Jena, Germany
    Exp Gerontol 45:410-8. 2010
  2. ncbi Oxidants, oxidative stress and the biology of ageing
    T Finkel
    Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
    Nature 408:239-47. 2000
  3. pmc Extending healthy life span--from yeast to humans
    Luigi Fontana
    Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 328:321-6. 2010
  4. ncbi The genetics of ageing
    Cynthia J Kenyon
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 464:504-12. 2010
  5. ncbi Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
    Konrad T Howitz
    BIOMOL Research Laboratories, Inc, 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
    Nature 425:191-6. 2003
  6. pmc Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
    David E Harrison
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Nature 460:392-5. 2009
  7. pmc Caloric restriction delays disease onset and mortality in rhesus monkeys
    Ricki J Colman
    Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
    Science 325:201-4. 2009
  8. ncbi Genetics of longevity in model organisms: debates and paradigm shifts
    David Gems
    Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
    Annu Rev Physiol 75:621-44. 2013
  9. pmc Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity
    Dudley W Lamming
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 335:1638-43. 2012
  10. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003

Detail Information

Publications362 found, 100 shown here

  1. ncbi How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)
    Michael Ristow
    Dept of Human Nutrition, Institute of Nutrition, University of Jena, Germany
    Exp Gerontol 45:410-8. 2010
    ..in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of ..
  2. ncbi Oxidants, oxidative stress and the biology of ageing
    T Finkel
    Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
    Nature 408:239-47. 2000
    ..Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span...
  3. pmc Extending healthy life span--from yeast to humans
    Luigi Fontana
    Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 328:321-6. 2010
    ..We discuss these findings and their potential application to prevention of age-related disease and promotion of healthy aging in humans, and the challenge of possible negative side effects...
  4. ncbi The genetics of ageing
    Cynthia J Kenyon
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 464:504-12. 2010
    ..Which genes can extend lifespan? Can we augment their activities and live even longer? After centuries of wistful poetry and wild imagination, we are now getting answers, often unexpected ones, to these fundamental questions...
  5. ncbi Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
    Konrad T Howitz
    BIOMOL Research Laboratories, Inc, 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA
    Nature 425:191-6. 2003
    ..We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators...
  6. pmc Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
    David E Harrison
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Nature 460:392-5. 2009
    ..These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases...
  7. pmc Caloric restriction delays disease onset and mortality in rhesus monkeys
    Ricki J Colman
    Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA
    Science 325:201-4. 2009
    ..Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species...
  8. ncbi Genetics of longevity in model organisms: debates and paradigm shifts
    David Gems
    Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
    Annu Rev Physiol 75:621-44. 2013
    ..Here we reexamine central concepts about the nature of aging...
  9. pmc Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity
    Dudley W Lamming
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 335:1638-43. 2012
    ..Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo...
  10. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003
    ....
  11. ncbi daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans
    K D Kimura
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 277:942-6. 1997
    ..Life-span regulation by insulin-like metabolic control is analogous to mammalian longevity enhancement induced by caloric restriction, suggesting a general link between metabolism, diapause, and longevity...
  12. pmc The cell-non-autonomous nature of electron transport chain-mediated longevity
    Jenni Durieux
    The Glenn Center for Aging Research, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Cell 144:79-91. 2011
    ..stress responses are essential and specific genetic requirements for the electron transport chain (ETC) longevity pathway...
  13. ncbi Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
    Judith Campisi
    Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    Cell 120:513-22. 2005
    ..Thus, the senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.
  14. ncbi Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans
    Claudio Franceschi
    Department of Experimental Pathology, University of Bologna, Via S Giacomo 12, 40126 Bologna, Italy
    Mech Ageing Dev 128:92-105. 2007
    ..Within this perspective, healthy aging and longevity are likely the result not only of a lower propensity to mount inflammatory responses but also of efficient anti-..
  15. ncbi Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
    Joseph T Rodgers
    Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 434:113-8. 2005
    ..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan...
  16. pmc Mitonuclear protein imbalance as a conserved longevity mechanism
    Riekelt H Houtkooper
    Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Federale de Lausanne, CH 1015 Lausanne, Switzerland
    Nature 497:451-7. 2013
    b>Longevity is regulated by a network of closely linked metabolic systems...
  17. pmc Recent progress in the biology and physiology of sirtuins
    Toren Finkel
    Translational Medicine Branch, National Heart Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 460:587-91. 2009
    ..Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live...
  18. ncbi FOXO transcription factors at the interface between longevity and tumor suppression
    Eric L Greer
    Department of Genetics, Stanford University, CA 94305, USA
    Oncogene 24:7410-25. 2005
    ..FOXO transcription factors are promising candidates to serve as molecular links between longevity and tumor suppression. These factors are major substrates of the protein kinase Akt...
  19. pmc Molecular evolution and functional characterization of Drosophila insulin-like peptides
    Sebastian Gronke
    Institute of Healthy Ageing, Department of Genetics, Evolution, and Environment, University College London, London, United Kingdom
    PLoS Genet 6:e1000857. 2010
    ..insulin/IGF signaling (IIS) pathway plays key roles in growth, metabolism, stress resistance, reproduction, and longevity in diverse organisms including mammals...
  20. 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...
  21. pmc Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster
    Ivana Bjedov
    Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, UK
    Cell Metab 11:35-46. 2010
    ..Analysis of the underlying mechanisms revealed that rapamycin increased longevity specifically through the TORC1 branch of the TOR pathway, through alterations to both autophagy and translation...
  22. ncbi Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
    Malene Hansen
    Department of Biochemistry and Biophysics, University of California, 600 16th Street, San Francisco, CA 94158, USA
    Aging Cell 6:95-110. 2007
    ..Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C...
  23. pmc Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila
    Camilla Burnett
    Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Gower Street, London WC1E 6BT, UK
    Nature 477:482-5. 2011
    ..In C. elegans, outcrossing of a line with high-level sir-2.1 overexpression abrogated the longevity increase, but did not abrogate sir-2.1 overexpression...
  24. pmc A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine
    Douglas C Wallace
    Center for Molecular and Mitochondrial Medicine and Genetics, Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697 3940, USA
    Annu Rev Genet 39:359-407. 2005
    ..Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today...
  25. ncbi Extending life span by increasing oxidative stress
    Michael Ristow
    Department of Human Nutrition, Institute of Nutrition, University of Jena, D 07743 Jena, Germany
    Free Radic Biol Med 51:327-36. 2011
    ..This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote ..
  26. ncbi Regulation of aging and age-related disease by DAF-16 and heat-shock factor
    Ao Lin Hsu
    Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143 2200, USA
    Science 300:1142-5. 2003
    ..activate expression of specific genes, including genes encoding small heat-shock proteins, which in turn promote longevity. The small heat-shock proteins also delay the onset of polyglutamine-expansion protein aggregation, suggesting ..
  27. ncbi Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
    H A Tissenbaum
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 410:227-30. 2001
    ..factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults...
  28. ncbi Ribosomal protein S6 kinase 1 signaling regulates mammalian life span
    Colin Selman
    Institute of Healthy Ageing, Centre for Diabetes and Endocrinology, Department of Medicine, University College London, London WC1E 6JJ, UK
    Science 326:140-4. 2009
    ..Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging...
  29. pmc Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans
    Jennifer M A Tullet
    Section on Developmental and Stem Cell Biology, Joslin Diabetes Center Department of Pathology, Harvard Medical School Harvard Stem Cell Institute, 1 Joslin Place, Boston, MA 02215, USA
    Cell 132:1025-38. 2008
    ..In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IIS-inhibited FOXO protein DAF-16. The C...
  30. pmc Mammalian sirtuins: biological insights and disease relevance
    Marcia C Haigis
    Glenn Laboratories for the Molecular Biology of Aging, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Pathol 5:253-95. 2010
    ..This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years...
  31. ncbi RPN-6 determines C. elegans longevity under proteotoxic stress conditions
    David Vilchez
    Howard Hughes Medical Institute, Glenn Center for Aging Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Nature 489:263-8. 2012
    ..elegans results in elevated somatic proteasome activity, clearance of damaged proteins and increased longevity. This activity is associated with increased expression of rpn-6, a subunit of the 19S proteasome, by the FOXO ..
  32. ncbi Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress
    Tim J Schulz
    Department of Human Nutrition, Institute of Nutrition, University of Jena, D 07743 Jena, Germany
    Cell Metab 6:280-93. 2007
    ....
  33. pmc TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO
    Stacey Robida-Stubbs
    Joslin Diabetes Center, Harvard Stem Cell Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02215, USA
    Cell Metab 15:713-24. 2012
    ..elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop...
  34. ncbi Induction of autophagy by spermidine promotes longevity
    Tobias Eisenberg
    Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
    Nat Cell Biol 11:1305-14. 2009
    ..Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.
  35. ncbi 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.
  36. pmc Genome sequencing reveals insights into physiology and longevity of the naked mole rat
    Eun Bae Kim
    Department of Bioinspired Science, Ewha Womans University, Seoul, 120 750, Korea
    Nature 479:223-7. 2011
    ..This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen...
  37. ncbi Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans)
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:683-8. 2010
    ..Therefore in humans the effect of CR may be somewhat blunted. Still how much does CR extend human lifespan? And could this extension be surpassed by gerosuppressants such as rapamycin?..
  38. pmc Lessons on longevity from budding yeast
    Matt Kaeberlein
    Department of Pathology, University of Washington, Seattle, Washington 98195, USA
    Nature 464:513-9. 2010
    ..Studies of budding yeast have made immense contributions to this progress. Yeast longevity factors have now been shown to modulate ageing in invertebrate and mammalian models, and studies of yeast have ..
  39. pmc Rapamycin extends maximal lifespan in cancer-prone mice
    Vladimir N Anisimov
    Department of Carcinogenesis and Oncogerontology, N N Petrov Research Institute of Oncology, St Petersburg, Russia
    Am J Pathol 176:2092-7. 2010
    ..Rapamycin dramatically delayed tumor onset as well as decreased the number of tumors per animal and tumor size. We suggest that, by slowing down organismal aging, rapamycin delays cancer...
  40. pmc Suppression of aging in mice by the hormone Klotho
    Hiroshi Kurosu
    Department of Pathology, University of Texas UT Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390 9072, USA
    Science 309:1829-33. 2005
    ..Klotho protein may function as an anti-aging hormone in mammals...
  41. pmc With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging
    Pankaj Kapahi
    Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Cell Metab 11:453-65. 2010
    ....
  42. pmc Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila
    Richard C Grandison
    Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, UK
    Nature 462:1061-4. 2009
    ..In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet...
  43. ncbi A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span
    Maria K Lehtinen
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 125:987-1001. 2006
    ..of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.
  44. pmc FOXO3A genotype is strongly associated with human longevity
    Bradley J Willcox
    Pacific Health Research Institute, 846 South Hotel Street, Honolulu, HI 96813, USA
    Proc Natl Acad Sci U S A 105:13987-92. 2008
    Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents...
  45. ncbi The endocrine regulation of aging by insulin-like signals
    Marc Tatar
    Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA
    Science 299:1346-51. 2003
    ....
  46. ncbi Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan
    Nataliya Libina
    Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 115:489-502. 2003
    In C. elegans, the transcription factor DAF-16 promotes longevity in response to reduced insulin/IGF-1 signaling or germline ablation. In this study, we have asked how different tissues interact to specify the lifespan of the animal...
  47. pmc Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice
    Richard A Miller
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109 2200, USA
    J Gerontol A Biol Sci Med Sci 66:191-201. 2011
    ....
  48. pmc Association of FOXO3A variation with human longevity confirmed in German centenarians
    Friederike Flachsbart
    Institute of Clinical Molecular Biology, Institute of Medical Informatics and Statistics, and Popgen Biobank, Christian Albrechts University, 24105 Kiel, Germany
    Proc Natl Acad Sci U S A 106:2700-5. 2009
    ..A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al...
  49. ncbi Extended longevity in mice lacking the insulin receptor in adipose tissue
    Matthias Bluher
    Joslin Diabetes Center and Department of Medicine, Harvard Medical School, One Joslin Place, Boston, MA, 02215 USA
    Science 299:572-4. 2003
    Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals...
  50. pmc Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila
    Cathy Slack
    Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, London, United Kingdom
    PLoS ONE 7:e47699. 2012
    ..We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster...
  51. ncbi Gene expression analysis of mTOR pathway: association with human longevity
    Willemijn M Passtoors
    Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
    Aging Cell 12:24-31. 2013
    ..been associated with human diseases such as diabetes and cancer, but has not been investigated for its impact on longevity per se...
  52. pmc Genetic signatures of exceptional longevity in humans
    Paola Sebastiani
    Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
    PLoS ONE 7:e29848. 2012
    Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors...
  53. pmc Regulation of Drosophila lifespan by JNK signaling
    Benoit Biteau
    Department of Biology, University of Rochester, Rochester, NY 14627, USA
    Exp Gerontol 46:349-54. 2011
    ..Here, we review recent studies in Drosophila that elucidate the tissue-specific and systemic consequences of JNK activation that ultimately impact lifespan of the organism...
  54. pmc Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity
    Seung Jae Lee
    Division of Molecular and Life Science, School of Interdisciplinary Bioscience and Bioengineering, and World Class University Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk 790 784, South Korea
    Curr Biol 20:2131-6. 2010
    ..Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration...
  55. ncbi Autophagy genes are essential for dauer development and life-span extension in C. elegans
    Alicia Melendez
    Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Science 301:1387-91. 2003
    ..elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans...
  56. pmc Lifespan regulation by evolutionarily conserved genes essential for viability
    Sean P Curran
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS Genet 3:e56. 2007
    ..Genes that are essential for growth and development are highly conserved in evolution, but their role in longevity has not previously been assessed...
  57. pmc SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span
    Tiara L A Kawahara
    Program in Epithelial Biology, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 136:62-74. 2009
    Members of the sirtuin (SIRT) family of NAD-dependent deacetylases promote longevity in multiple organisms...
  58. pmc Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila
    Gabor Juhasz
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Genes Dev 21:3061-6. 2007
    ..Thus, normal levels of autophagy are crucial for stress survival and continuous cellular renewal, but not metamorphosis...
  59. ncbi Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling
    K Lin
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA
    Nat Genet 28:139-45. 2001
    ..Together these findings reveal unexpected complexity in the DAF-16-dependent pathways that regulate aging...
  60. ncbi Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal
    Kim Zarse
    Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
    Cell Metab 15:451-65. 2012
    ..Inhibition of this ROS signal by antioxidants reduces iIIS-mediated longevity by up to 60%...
  61. 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
    ..Partial loss-of-function mutations in these genes decrease electron transport and greatly increase the longevity of C. elegans by a mechanism that is distinct from that induced by reducing their level of expression by RNAi...
  62. pmc Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span
    Kevin J Pearson
    Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Cell Metab 8:157-68. 2008
    ..Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.
  63. pmc Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf
    Riva P Oliveira
    Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, One Joslin Place, Boston, MA 02215, USA
    Aging Cell 8:524-41. 2009
    ..elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways...
  64. pmc MicroRNAs both promote and antagonize longevity in C. elegans
    Alexandre de Lencastre
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511 USA
    Curr Biol 20:2159-68. 2010
    ..elegans, but the mechanisms of life-span regulation are not completely known. MicroRNAs (miRNAs) regulate various aspects of development and metabolism, and one miRNA has been previously implicated in life span...
  65. 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...
  66. ncbi Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice
    Colin Selman
    Centre for Diabetes and Endocrinology, Department of Medicine, Rayne Institute, University College London, University St, London, UK
    FASEB J 22:807-18. 2008
    ..Thus, enhanced insulin sensitivity is not a prerequisite for IIS mutant longevity. Irs1-/- female mice also displayed normal anterior pituitary function, distinguishing them from long-lived ..
  67. ncbi Genome-wide miRNA signatures of human longevity
    Abdou ElSharawy
    Institute of Clinical Molecular Biology, Christian Albrechts University, Schittenhelmstraße 12, D 24105 Kiel, Germany
    Aging Cell 11:607-16. 2012
    Little is known about the functions of miRNAs in human longevity. Here, we present the first genome-wide miRNA study in long-lived individuals (LLI) who are considered a model for healthy aging...
  68. pmc The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling
    Laurent Mouchiroud
    Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    Cell 154:430-41. 2013
    ..genetic or pharmacological restoration of NAD(+) prevents age-associated metabolic decline and promotes longevity in worms. These effects are dependent upon the protein deacetylase sir-2...
  69. ncbi XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity
    Rebecca C Taylor
    The Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA 94720, USA
    Cell 153:1435-47. 2013
    ..Neuronally derived XBP-1s was sufficient to rescue stress resistance, increase longevity, and activate the UPR(ER) in distal, non-neuronal cell types through a cell-nonautonomous mechanism...
  70. pmc Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways
    David E Shore
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS Genet 8:e1002792. 2012
    ..resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for ..
  71. ncbi Extension of murine life span by overexpression of catalase targeted to mitochondria
    Samuel E Schriner
    Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA
    Science 308:1909-11. 2005
    To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT)...
  72. pmc Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination
    Nuno M V Gomes
    Department of Cell Biology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9039, USA
    Aging Cell 10:761-8. 2011
    ....
  73. pmc Extreme longevity is associated with increased serum thyrotropin
    Gil Atzmon
    Department of MedicineDivision of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Clin Endocrinol Metab 94:1251-4. 2009
    ..The distribution of serum TSH shifts progressively to higher concentrations with age...
  74. pmc Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels
    Rong Yuan
    The Jackson Aging Center at The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Aging Cell 8:277-87. 2009
    ..53, P < 0.01). These results support the hypothesis that the IGF1 pathway plays a key role in regulating longevity in mice and indicates that common genetic mechanisms may exist for regulating IGF1 levels and lifespan.
  75. ncbi 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
    ..However, no causal role of any hormonal signal in diet-restricted longevity has been demonstrated...
  76. pmc Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans
    Eric L Greer
    Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA
    Nature 479:365-71. 2011
    ..Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendants.
  77. pmc OASIS: online application for the survival analysis of lifespan assays performed in aging research
    Jae Seong Yang
    School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, South Korea
    PLoS ONE 6:e23525. 2011
    ..To capture the different effects of genetic and environmental factors on lifespan, appropriate statistical analyses are needed...
  78. pmc Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited
    Joris Deelen
    Section of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Aging Cell 10:686-98. 2011
    By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging...
  79. pmc Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands
    Susan J Broughton
    Department of Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom
    Proc Natl Acad Sci U S A 102:3105-10. 2005
    ..However, the ablated flies show an extension of median and maximal lifespan and increased resistance to oxidative stress and starvation...
  80. ncbi p53 mutant mice that display early ageing-associated phenotypes
    Stuart D Tyner
    Cell and Molecular Biology Program, Baylor College of Medicine, Houston, TX 77030, USA
    Nature 415:45-53. 2002
    ..As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance...
  81. ncbi Demography. Broken limits to life expectancy
    Jim Oeppen
    Cambridge Group for the History of Population and Social Structure, Cambridge University, Cambridge, CB2 3EN, UK
    Science 296:1029-31. 2002
  82. ncbi Cost of mating in Drosophila melanogaster females is mediated by male accessory gland products
    T Chapman
    ICAPB, University of Edinburgh, UK
    Nature 373:241-4. 1995
    ..The cost of mating to females may therefore represent a side-effect of evolutionary conflict between males...
  83. pmc 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila
    Brian M Zid
    California Institute of Technology, Pasadena, CA 91125, USA
    Cell 139:149-60. 2009
    ..For a video summary of this article, see the PaperFlick file with the Supplemental Data available online...
  84. ncbi Delayed ageing through damage protection by the Arf/p53 pathway
    Ander Matheu
    Tumor Suppression Group, Spanish National Cancer Research Centre CNIO, Madrid 28029, Spain
    Nature 448:375-9. 2007
    ..These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.
  85. ncbi Influence of temperature on immature development, survival, longevity, fecundity, and gonotrophic cycles of Aedes albopictus, vector of chikungunya and dengue in the Indian Ocean
    H Delatte
    Research Unit 016, Institut de recherche pour le developpement IRD, 7 chemin de l IRAT, 97410 Saint Pierre, La Reunion, France
    J Med Entomol 46:33-41. 2009
    ..Therefore, the immature development, survival, longevity, fecundity, and gonotrophic cycles of Ae. albopictus were studied for an F2 population of the IO...
  86. pmc Lifespan and reproduction in Drosophila: New insights from nutritional geometry
    Kwang Pum Lee
    School of Biological Sciences and Centre for Mathematical Biology, University of Sydney, Sydney NSW 2006, Australia
    Proc Natl Acad Sci U S A 105:2498-503. 2008
    ..Response surfaces for lifespan and fecundity were maximized at different protein-carbohydrate intakes, with longevity highest at a protein-to-carbohydrate ratio of 1:16 and egg-laying rate maximized at 1:2...
  87. pmc Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans
    Eric L Greer
    Department of Genetics, Stanford University, Stanford, CA 94305, USA
    Aging Cell 8:113-27. 2009
    ..Here we examine the genetic pathways that mediate longevity by different DR regimens in Caenorhabditis elegans...
  88. ncbi The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans
    Y Honda
    Tokyo Metropolitan Institute of Gerontology, Tokyo 173 0015, Japan
    FASEB J 13:1385-93. 1999
    b>Longevity is regulated by the daf-2 gene network in Caenorhabditis elegans...
  89. ncbi The p66shc adaptor protein controls oxidative stress response and life span in mammals
    E Migliaccio
    Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
    Nature 402:309-13. 1999
    ..We propose that p66shc is part of a signal transduction pathway that regulates stress apoptotic responses and life span in mammals...
  90. ncbi Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study
    Manja Schoenmaker
    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Hum Genet 14:79-84. 2006
    We conducted a sib pair study in very old subjects for the purpose of mapping longevity loci...
  91. ncbi A database of vertebrate longevity records and their relation to other life-history traits
    J P de Magalhaes
    School of Biological Sciences, University of Liverpool, Liverpool, UK
    J Evol Biol 22:1770-4. 2009
    b>Longevity is a major characteristic of animals that has long fascinated scientists...
  92. pmc Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity
    Ludmila Pawlikowska
    Department of Anesthesia and Perioperative Care, University of California, San Francisco, USA
    Aging Cell 8:460-72. 2009
    ..We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males ..
  93. ncbi Long-lived C. elegans daf-2 mutants are resistant to bacterial pathogens
    Danielle A Garsin
    Department of Genetics, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 300:1921. 2003
  94. pmc Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator
    Ji Li
    Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA
    PLoS Biol 6:e233. 2008
    The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown...
  95. pmc Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density
    Yong Pan
    Department of Pathology, Yale University School of Medicine, New Haven CT 06520, USA
    Aging (Albany NY) 1:131-45. 2009
    ....
  96. pmc Puzzles, promises and a cure for ageing
    Jan Vijg
    Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA
    Nature 454:1065-71. 2008
    ..A better understanding of the targets of such interventions, as well as the proximate causes of ageing-related degeneration and disease, is essential before we can evaluate if abrogation of human senescence is a realistic prospect...
  97. pmc Downregulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms
    Saula Vigili de Kreutzenberg
    Department of Clinical and Experimental Medicine, Metabolic Diseases, University of Padova, Padova, Italy
    Diabetes 59:1006-15. 2010
    ..We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro...
  98. ncbi Sirtuin activators mimic caloric restriction and delay ageing in metazoans
    Jason G Wood
    Department of Pathology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 430:686-9. 2004
    ..Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction...
  99. pmc Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity
    Marian Beekman
    Molecular Epidemiology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
    Proc Natl Acad Sci U S A 107:18046-9. 2010
    ..and type 2 diabetes as identified by genome-wide association studies was tested for compatibility with human longevity. Here, we show that nonagenarian siblings from long-lived families and singletons older than 85 y of age from ..
  100. ncbi Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study
    Maarten P Rozing
    Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
    J Am Geriatr Soc 58:564-9. 2010
    To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity.
  101. ncbi Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition
    Mikhail V Blagosklonny
    Cell Cycle 5:2087-102. 2006
    ..animals from worms to mammals caloric restrictions, life-extending agents, and numerous mutations that increase longevity all converge on the TOR pathway...

Research Grants73

  1. Regulation of mural cells during pulmonary capillary formation
    Stephen E McGowan; Fiscal Year: 2013
    ..pathways in LF and pericytes alters (a) the capillary meshwork and (b) pericyte and LF proliferation and longevity. Important signaling pathways, which are initiated by PDGFs, are mediated by Abelson kinase and Rac1, and alter ..
  2. Non-viral Genetic Modification of Antigen-presenting Cells in Allografts
    Wilson S Meng; Fiscal Year: 2011
    ..It aims to test if the longevity of transplants can be extended by forcing white blood cells associated with transplant organs to produce ..
  3. Role of SCD1 and Dietary Methionine Restriction on Energy Homeostasis
    ERIC PAUL PLAISANCE; Fiscal Year: 2011
    ..Dietary methionine restriction (MR) has been used as a mimetic of caloric restriction to increase longevity in rodents...
  4. Response to and signals of caloric restriction and intermittent feeding regimens
    MARC KOPEL HELLERSTEIN; Fiscal Year: 2010
    ..5) Determine whether biomarker-based outcome measures predict effects on hard clinical outcomes, through longevity studies and studies in disease models (ApoE k.o. and LDL-receptor k.o...
  5. Mucosal Immunity, Vaccines and Microbiota Interplay in Humans and Animal
    Marcelo B Sztein; Fiscal Year: 2013
    ..dysenteriae 1 and longevity of the responses to vaccination in humans, (3) To evaluate the effects of immunization of monkeys with ..
  6. Prolonged Inhibition of Pathologic Neovascularization by Catalytic Antioxidants
    JAMES FRANCIS MCGINNIS; Fiscal Year: 2013
    ..Expected outcomes - the work proposed is expected to demonstrate the longevity, potency and mechanisms by which nanoceria inhibit pathologic neovascularization in the retina...
  7. Clinical , Mechanical and Chemical Evaluation of Amalgam and ART Restorations
    Lilliam Marie Pinzon; Fiscal Year: 2013
    ..successful than conventional dental treatments for large carious lesions with respect to increased restoration longevity and decreased caries recurrence...
  8. Sirtuin/FOXO Signaling in the Regulation of Bone Mass
    Stavroula Kousteni; Fiscal Year: 2012
    ..These studies will provide for the first time a link between pathways that regulate oxidative stress, longevity and skeletal homeostasis under the control of the Sirtuin/FOXO system...
  9. Early Life Conditions, Survival, and Health: A Pedigree-Based Population Study
    Ken R Smith; Fiscal Year: 2013
    ..is based on the Utah Population Database (UPDB) and links biomarker data collected from two studies: Fertility, Longevity &Aging study (FLAG) and the Cache County Memory Study (CCMS)...
  10. The Somatotropic Axis and Health Aging: A Search for Mechanisms
    Andrzej Bartke; Fiscal Year: 2013
    ..research is to identify mechanisms responsible for the effects of growth hormone (GH) signaling on aging and longevity in mammals...
  11. Neuroimaging Assessments of Brain Integrity in Aging Mice
    Ai Ling Lin; Fiscal Year: 2013
    ..CR perhaps is the most well-studied one for various model organisms of extended longevity, including Saccharomyces cerevisiae, Caenorhabditis elegans, rodents and monkeys...
  12. Mucosal Memory T Cells at the Vanguard of Human Host Defense
    Donna L Farber; Fiscal Year: 2010
    ..In the proposed research, we will take a novel "whole-body" approach to investigate the functional potential and longevity of human mucosal memory T cells obtained from individual organ donors, with a focus on the lung and intestine as ..
  13. Lifespan Extension Despite Greatly Elevated Insulin and Body Fat
    David E Harrison; Fiscal Year: 2013
    ..from patterns typical of insulin resistance, hyperinsulinemia and obesity to patterns typical of DR and extended longevity. Key intermediates of these pathways will be tested in liver and gastrocnemius muscle, using western blots to ..
  14. CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION
    Steven G Clarke; Fiscal Year: 2013
    ..and the responses of the insulin/insulin-like signaling system to increase stress resistance and longevity. We will test several hypotheses to explain the physiological role of the linkage, including direct recognition ..
  15. Optic Nerve Aging and Glaucoma
    Thasarat Vajaranant; Fiscal Year: 2013
    ..Worldwide, women comprise 59% of those affected by glaucoma, due in large part to their greater longevity. Women are also at risk for visual loss from glaucoma because they are 24% less likely to be treated for this ..
  16. Developmental Origins of Phenotypic Characteristics that Predict Longevity
    Andrzej Bartke; Fiscal Year: 2012
    ..started at different stages of postnatal development, can influence phenotypic characteristics associated with longevity and whether the hormone-induced alterations in these characteristics will persist after the treatment is stopped...
  17. Molecular Genetics of Caloric Restriction in Aging Flies
    Blanka Rogina; Fiscal Year: 2013
    ..made significant contributions to our understanding of the effects of age and caloric intake on physiology and longevity of adult Drosophila...
  18. The Greatest Generation: The NAS-NRC WWII Twin Registry as a Scientific Resource
    Margaret Gatz; Fiscal Year: 2012
    ..For example, we will evaluate socioeconomic and cognitive differences in health outcomes and longevity over the lifecycle...
  19. Systemic Factors that Maintain a Young Liver Phenotype
    Roy G Smith; Fiscal Year: 2012
    ..Caloric restriction (CR) maintains health during aging and increases longevity;however, the molecular mediator(s) is unknown...
  20. The AMP-activated protein kinase (AMPK) antagonizes inflammation through SIRT1
    Hang Shi; Fiscal Year: 2012
    ..as an energy sensor, is an NAD+dependent deacetylase that mediates the effects of caloric restriction to extend longevity. AMPK and SIRT1 show striking similarities in sensing nutrient supply and regulating metabolic pathways and are ..
  21. Laser Spinning Disc Confocal System for live-cell and live-organism microscopy
    Martha C Soto; Fiscal Year: 2012
    ..C. elegans studies of longevity and neurodegeneration in the Driscoll lab are identifying the processes and the molecules that control lifespan ..
  22. Generating Blood-based Diagnosis for Alzheimer Disease
    Eugenia Wang; Fiscal Year: 2012
    ..SIRT1 is a member of the 7-member Silent Information Regulator protein family. Caloric restriction extends longevity through triggering expression of SIRT1, which can also be mimicked by resveratrol, a red wine polyphenol...
  23. Akt, cellular senescence, and lifespan
    Nissim Hay; Fiscal Year: 2010
    ..However, the contribution of the PISK/Akt signaling pathway to longevity in mammals has not been thoroughly explored...
  24. The development of probiotic yeast as an inexpensive vaccine delivery platform
    TRACEY JANE LAMB; Fiscal Year: 2013
    ..I will also examine the longevity of the immune responses generated by this vaccine delivery platform by assaying for memory responses (..
  25. Alterations in membrane composition and function eith calorie restriction
    Jon J Ramsey; Fiscal Year: 2011
    ..It has been proposed that the degree of membrane fatty acid unsaturation is a major factor contributing to longevity, and that a decrease in membrane unsaturation may be the mechanism for the retardation of aging with CR...
  26. Monogonont Rotifers as a Model to Investigate the Biology of Aging
    Terry W Snell; Fiscal Year: 2013
    ..as well as homeostasis and tissue regeneration, the effects of reproductive mode (asexual versus sexual) on longevity, and the cellular and molecular processes of senescence...
  27. The role of XMRV, a newly discovered human retrovirus, in cancer pathogenesis
    Ila R Singh; Fiscal Year: 2013
    ..Morbidity and mortality due to prostate cancer are likely to grow further given increasing longevity. Epidemiologic studies indicate that infection and inflammation may play a role in the development of prostate ..
  28. Coping Skills Training in Heart Failure: Outcomes and Mechanisms
    Andrew Sherwood; Fiscal Year: 2013
    ..self- management behavioral interventions as cost-effective approaches to enhance disease management, QoL and longevity in HF patients...
  29. AREA: Rapamycin, ambient temperature, and longevity
    Steven J Swoap; Fiscal Year: 2010
    ..Swoap Title - AREA: Rapamycin, ambient temperature, and longevity in mice Until recently, additives to the diet have been unable to mimic the lifespan-extension effects of ..
  30. REACTIVE OXYGEN SPECIES AND AGING
    Elias K Michaelis; Fiscal Year: 2012
    ..cellular aspects of aging has greatly expanded our understanding of the basic processes that contribute to both longevity and age-related diseases...
  31. Roles for Global Chromatin Structure in C. elegans Longevity
    Siu Sylvia Lee; Fiscal Year: 2010
    Recent research has revealed many evolutionarily conserved genetic pathways important for longevity. In contrast, relatively little is known about the role of epigenetic changes in organismal aging...
  32. DEVELOPMENT AND MAINTENANCE OF LENS TRANSPARENCY
    JOHN IRWIN CLARK; Fiscal Year: 2013
    ..With the increase in human longevity, the impact of aging diseases is increasing dramatically...
  33. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
    ..In particular, we seek to improve the longevity of SMA mice...
  34. Mechanisms of Lipid-Induced Hepatic Insulin Resistance
    Gerald I Shulman; Fiscal Year: 2013
    ..INDY encodes a non-electrogenic dicarboxylate and citrate transporter and has been shown to promote longevity in a manner akin to caloric restriction in flies, but its role in mammals is unknown...
  35. Targeting Sirtuin-1 to enhance Foxp3+ regulatory T-cell function
    Ulf Beier; Fiscal Year: 2013
    ..a class III HDAC highly conserved across eukaryotic species and an important mediator of cellular metabolism and longevity, in Tregs...
  36. TSQ Vantage Bundle with Acquity UltraPerformance LC
    Nicolaas E Deutz; Fiscal Year: 2010
    ..Since Drs. Wolfe and Deutz, founders of the Center for Translational Research in Aging and Longevity (CTRAL, Donald W...
  37. Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)
    Pilar Blancafort; Fiscal Year: 2013
    ..In Aim2 we monitor the longevity of the silencing implemented by the 6ZF- silencers...
  38. Cytoglobin: A stress-responsive hemoprotein modulating cardiomyocyte survival
    Pradeep P A Mammen; Fiscal Year: 2013
    ..cardiac remodeling is a major goal in the pursuit of new treatment approaches for improving the quality and longevity of heart failure patients...
  39. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Ronald Kahn; Fiscal Year: 2013
    ..on how tissues communicate with one another in insulin resistant states, a role for insulin signaling in fat in longevity and a role for insulin signaling in the brain in neurodegeneration...
  40. Novel neurotrophic therapy in a mouse model of ALS
    Alpaslan Dedeoglu; Fiscal Year: 2013
    ..We will monitor the effects of 7,8-DHF administration on body weight, motor performance and longevity and examine the effects on motor neuron and ventral horn changes in size, number, dendritic branching, spine ..
  41. Molecular Mechanisms of Age-related Impairment of Muscle Regeneration
    Thomas A Rando; Fiscal Year: 2013
    ..3) To explore the molecular interactions between the Wnt signaling pathway with two key "longevity genes", SIRT1 and Klotho, and the functional significance of these interactions in terms of stem cell ..
  42. The Role of TAF4b in Spermatogonial Stem Cell Maintenance and Self-Renewal
    Eric Gustafson; Fiscal Year: 2013
    ..Several lines of evidence suggest it plays an essential role in spermatogonia stem cell (SSC) self-renewal and longevity. One of the specific aims in this research proposal is to identify and characterize TAF4b-interacting protein ..
  43. Neural control of adaptive Beta-cell growth in insulin resistant rats
    WILLIAM CHARLES DIAZ; Fiscal Year: 2011
    ..Contributing factors to BCM are hypertrophy of existing cells, proliferation, augmented longevity and the neogenesis of new ss-cells from existing progenitor populations...
  44. New composite material design based on studies of tooth-composite and microbial i
    J Paul Santerre; Fiscal Year: 2013
    ..materials with increased resistant to bacterial invasion and ultimately increasing the restoration's longevity. Objective: To study the degradation of resin-tooth interfacial margins with an in vitro simulated human oral ..
  45. Toll-like receptor signaling in the generation of B1b cell memory
    Kishore R Alugupalli; Fiscal Year: 2012
    ..Persistence of memory B cells generated by vaccination is critical for the longevity of protective immunity, but the molecular mechanism required for their long-term maintenance is unknown...
  46. TR4 orphan receptor, a longevity assurance gene, in prostate carcinogenesis
    Yi Fen Lee; Fiscal Year: 2012
    ..Our study will lead to more accurate diagnosis and better prognosis for prostate cancer, and facilitate genetic or pharmacological intervention to slow this disease by utilizing TR4. ..
  47. Dynamics of Transcriptional Regulation
    Elena Zelin; Fiscal Year: 2011
    ..test the hypothesis that the p23 molecular chaperone disengages DNA-bound transcription factors and that the longevity of the dissociation is mediated through reversible acetylation/deacetylation of an affected DNA binding domain...
  48. IGF-1, Gender, Heart Failure and Longevity: A Paradigm Shift
    Piero Anversa; Fiscal Year: 2010
    ..Thus, the genetic-molecular status of the heart may condition the outcome of aging and genetic manipulations may interfere with the development of the cardiac senescent phenotype in both genders. ..
  49. Molecular mechanisms of neural plasticity in drug addiction
    LAURA NICOLE SMITH; Fiscal Year: 2010
    ..Since drug-induced sensitization in rodents is used to model the longevity of addiction, understanding mechanisms influencing this behavior, as well as associated brain adaptations, ..
  50. Regulation of SKN-1 functions by insulin-like signaling in C. elegans
    THOMAS KEITH BLACKWELL; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Insulin/IGF-1 signalling (IIS) profoundly influences stress resistance and longevity in diverse organisms, possibly including humans...
  51. ANALYSIS OF A NOVEL SUBSET OF HUMAN CD8+ MEMORY CELLS WITH STEM CELL QUALITIES
    Stanley R Riddell; Fiscal Year: 2010
    ..Progress in defining the qualitative attributes of memory T cells that contribute to their longevity has been much less significant, particularly in humans...
  52. MECHANISMS OF SYNERGISTIC REGULATION OF STEM/PROGENITORS
    Hal E Broxmeyer; Fiscal Year: 2013
    ..Sirt1, a member of the Sirtuin family of deacetylases, has been linked to longevity and stress tolerance in budding yeast and other lower eukaryocytes, and to aging, metabolism and stress ..
  53. Genes required for lipid processing and digestive organ function in larval zebraf
    Steven A Farber; Fiscal Year: 2011
    A number of widespread diseases that impact both quality of life and longevity are influenced by dietary fat...
  54. Long-lived B cell Immunity in the Respiratory Tract
    Nicole Baumgarth; Fiscal Year: 2013
    ..plasma cells/precursors in the lung tissue and BrDU labeling studies to identify the mechanisms underlying the longevity of the antibody-secreting cells in the lung...
  55. NOVEL APPROACHES FOR REGULATION OF IGF-1 LEVELS THROUGHOUT THE LIFESPAN
    William Edmund Sonntag; Fiscal Year: 2013
    ..The question of whether reduced GH and IGF-1 levels are directly associated with increased longevity and whether GH and/or IGF-1 replacement have beneficial effects on individual organ systems (e.g...
  56. Metabolic and Energetic Consequences of Fatherhood
    Wendy Saltzman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Fatherhood can influence health and longevity in men...
  57. Role of 12/15-lipoxygenase in mechanisms of muscle atrophy during aging
    Arunabh Bhattacharya; Fiscal Year: 2013
    ..As a faculty member of the Department of CSB/Barshop Institute for Longevity and Aging Studies in San Antonio, he has been studying the role of lipid mediators generated by the inflammatory ..
  58. Oxaloacetate's Brain Effects
    Russell H Swerdlow; Fiscal Year: 2013
    ..One manufacturer markets it as a caloric restriction mimetic and "longevity supplement". These claims are based on a 2009 study in which OAA-treated C...
  59. Molecular Mechanisms of Rapamycin's effects on Health and longevity.
    Joseph A Baur; Fiscal Year: 2013
    ..insulin sensitization and increased mitochondrial biogenesis have been suggested to contribute to CR-induced longevity. We recently showed that rapamycin-induced insulin resistance is the result of inhibiting a second target, ..
  60. A family of novel mitochondrially-encoded peptides and their role in aging
    Pinchas Cohen; Fiscal Year: 2012
    ..Our approach will involve genomic and proteomic approaches in humans with exceptional longevity and in relevant mouse models of aging...
  61. IGF-1, oxidative stress and telomere dynamics in cultured human somatic cells
    Rivka C Stone; Fiscal Year: 2012
    ..interrelated mechanisms could account for the often conflicting conclusions about the role of IGF-1 in aging and longevity of lower organisms (the worm, fly), short-lived mammals (mouse) and humans...
  62. Analyzing the Efficacy of Galectin-1 Ligand Inhibition in Adoptive T cell Therapy
    JENNA GEDDES SWEENEY; Fiscal Year: 2012
    ..interactions on antigen-specific CTLs, prior to adoptive immunotherapy, could help circumvent current shortcomings, such as T cell susceptibility to tumor- derived Gal-1 and longevity in vivo, thereby enhancing anti-tumor efficacy.
  63. THE BIODEMOGRAPHY OF HUMAN LONGEVITY--A TRAINING PROGRAM
    Leonid Gavrilov; Fiscal Year: 2005
    ..the investigator with an opportunity to develop his career as an independent scientist in the biodemography of longevity. He has changed both his research approach (from studies of aggregated demographic life tables to the analysis ..
  64. Frontiers in Statistical Genetics for NIAMS Researchers
    Hemant Tiwari; Fiscal Year: 2005
    Obesity is associated with diseases such as diabetes and heart disease and with decreased longevity. This might suggest that, among obese individuals, weight loss will increase longevity, but this has yet to be demonstrated...
  65. Identifying New Aging and Longevity Genes in Caenorhabditis elegans
    Muneesh Tewari; Fiscal Year: 2007
    ..He has developed an interest in aging and longevity and wishes to pursue a program of career development that will provide training in the areas of (1) biology of ..
  66. Role of Genes in Exceptional Longevity in Humans
    NIR J BARZILAI; Fiscal Year: 2012
    ..evidence for a substantial genetic component, the inherited biological factors that promote extended life span (longevity) in humans remain unknown...
  67. Hormonal signals, genome integrity and longevity
    Jan Vijg; Fiscal Year: 2009
    ..To investigate if in a mouse model of extended longevity the rate of mutation accumulation would be slower, and the mutation spectra different, we crossed the lacZ ..
  68. DOES WEIGHT LOSS REDUCE MORTALITY RATE AMONG OBESE RATS?
    David Allison; Fiscal Year: 2002
    Obesity is increasingly prevalent and associated with decreased longevity and adverse health conditions...
  69. LONGEVITY AND ELDERLY HEALTH CARE EXPENDITURES
    EDWARD NORTON; Fiscal Year: 2001
    ..care expenditures depend in part on time until death, with higher expenditures prior to death, so increased longevity may merely push expenditures further into the future...
  70. NAD+ control of transcriptional silencing and longevity
    David Sinclair; Fiscal Year: 2007
    ..as a promising model for understanding the molecular basis for the link between calorie intake, stress and longevity. One major cause of yeast aging stems from the instability of the highly repetitive ribosomal DNA (rDNA) locus...
  71. Inositol Signaling in C. elegans Senescence and Diapause
    GARY B RUVKUN; Fiscal Year: 2010
    ..An insulin-like signaling pathway regulates longevity and metabolism in C. elegans...
  72. Genetics of Longevity in Long-Lived Siblings
    Sangkyu Kim; Fiscal Year: 2010
    ..2004 as postdoctoral associate, I've been participating in two research projects to study genetics of human longevity, as part of multidisciplinary programs...
  73. PACIFIC GENETIC EPIDEMIOLOGIC STUDY ON AGING
    J Curb; Fiscal Year: 2002
    ..Epidemiological, family, and twin studies suggest that a substantial proportion of the phenotypic variation in longevity and functional ability is genetic...