Select a year 1998 1999 2000 2001 2002 2003    Select a researcher Frederick W. Alt, Ph.D Bruce N. Ames, Ph.D. Spyridon Artavanis-Tsakonas, Ph.D. Giuseppe Attardi, M.D. Steven N. Austad, Ph.D. Tamas Bartfai, Ph. D. Andrzej Bartke, Ph.D. Nir Barzilai, M.D. Seymour Benzer, Ph.D. Seymour Benzer, Ph.D. Helen M. Blau, Ph.D. Roger Brent, Ph. D. Linda B. Buck, Ph. D. Jochen Buck, M.D., Ph.D. Judith Campisi, Ph.D. Luca Cavalli-Sforza, M.D. Catherine F. Clarke, Ph.D., co-PI James E. Cleaver, Ph.D. Stanley N. Cohen, M.D. Gretchen J. Darlington, Ph.D. Titia de Lange, M.D. , Ph.D. Ronald A. DePinho, M.D. Stephen J. Elledge, Ph.D. Art Gafni, Ph.D. Lawrence S.B. Goldstein, Ph.D. Daniel E. Gottschling, Ph.D. Michael E. Greenberg, Ph.D. Paul Greengard, Ph.D. Carol W. Greider, Ph.D. Jack D. Griffith, Ph. D. Leonard Guarente, Ph.D. Philip C. Hanawalt, Ph. D. Stephen Helfand, M.D. Peter J. Hornsby, Ph. D. Thomas E. Johnson, Ph.D. Cynthia J. Kenyon, Ph.D. Cynthia J. Kenyon, Ph.D. Stuart Kim, Ph.D. Thomas Kornberg, Ph. D. Pamela L. Larsen, Ph.D., co-PI Jeff W. Lichtman, M.D., Ph.D. Charles M. Lieber, Ph. D. Susan L. Lindquist, Ph.D. Stuart Lipton, M.D., Ph.D. Gordon Lithgow, Ph.D. Lawrence A. Loeb, M.D., Ph.D. Victoria Lundblad, Ph.D. Mark Mayford, Ph.D. Simon Melov, Ph.D. James F. Nelson, Ph.D. Fernando Nottebohm, Ph.D. Olivia M. Pereira-Smith, Ph.D. Thomas Perls, M.D., M.P.H Gregory A. Petsko, D. Phil. Daniel Promislow, Ph.D. Fred E. Regnier, Ph.D, co-PI Arlan G. Richardson, Ph.D, co-PI David Ron, Ph. D. Gary Ruvkun, Ph.D. Thomas P. Sakmar, M.D. Joshua R. Sanes, Ph.D Jerry W Shay, Ph.D. James L. Sherley, M.D., Ph.D. Sangram S. Sisodia, Ph. D. Rudolph E. Tanzi, Ph.D. David S. Thaler, Ph.D. John Tower, Ph.D. Eric Verdin, M.D. Douglas C. Wallace, Ph.D. Robert A. Weinberg, Ph.D. Sherman M. Weissman, M.D. Phyllis M. Wise, Ph.D. Woodring E. Wright, M.D., Ph.D. Select a project Translating Yeast Telomere Biology to Human Cells: Identi...A High Throughput Screen for Longevity GenesA Novel Class of Aging Genes in Drosophila melanogasterA Novel Proteomic Approach to Identifying, Sequencing, and...Aging in Mutator and Antimutator MiceAging-dependent Large Accumulation of Mutations at Specifi...Analysis of genes that control aging in C. elegansBicarbonate-activated adenylyl cyclase and agingBone Marrow to Brain: Searching for markers of bone marrow...Can the Heat-Shock Response Extend the Lifespan of the Mou...Cell Physiologic Stresses and Telomere-Based Cell SenescenceCell Transplantation Models for Gene Action in Human AgingChronic Neuroprotection during Aging by UCP Mediated Simul...Connections Between the Telomere Sensing and DNA Damage Ac...Critically Testing the Free Radical Theory of Aging, and D...Early Hormonal Signaling and Longevity: Role of Long-term ...Endogenous DNA Damage and Mechanisms of AgingEstradiol is a Neuroprotective Factor in the Aging Brain: ...Exploration of the C.elegans insulin-like aging pathwayExploring the genetics of extreme longevityFunctional Tests of Replicative Aging in Organotypic Skin ...Gene-gene interactions, gene networks and aging in natural...Genes Controlling Longevity in CentenariansGenetic Dissection of Aging in DrosophilaGenetic Mechanisms of Exceptional Oxidative Damage Resista...Genetic Mechanisms Regulating Replicative Aging in Diffier...Genomic approaches to studying aging in C. elegansHow cells die in Alzheimer's and other neurodegenerati...Hypothesis to be tested: some aspects of functional aging ...Identification of Candidate Genes for Longevity in Long Li...Identification of Chemical “Age Spots” on Immortal DNA Str...Identification of gerontogenes in the mouseIdentification of Longevity Genes in Founder PopulationsIdentification of Protein Regulators of Self-renewal, Diff...Intersection of two pathways in control of aging: nutritio...Investigating the Potential Involvement of Cellular Qualit...Life extension genes in DrosophilaMitochondrial Aging in the ChimpanzeeMitochondrial Mutation and AgingMitochondrial swirls, a link between oxidative stress and ...Molecular analysis of mammalian agingMolecular Determinants of Hippocampal Neuroplasticity in a...Molecular through Cellular Changes Responsible for Alzheim...Mutagenic Screen for Longevity Genes in MiceNovel APP - containing synaptic organelles and Alzheimer&#...Probing the role of axonal transport disturbance and trans...Proteotoxicity and AgingRapid Screening for Longevity Mutants in MiceRepair of Oxidative DNA Damage in Human NeuronsReplicative senescence in S. cerevisiaReplicative Senescence of Drosophila Stem Cells in VivoReversal of Mitochondrial Decay: From Rats to HumansRole of a SIRT3, a Sir2-related Mitochondrial Protein Deac...Role of telomeres and telomerase in human agingRole of the multiligand receptor, LRP. In Alzheimer’s dise...Single Molecule Studies of Age-Related Alterations in Heat...Telomere Looping and Control of Cell AgingTelomeres, Cell Phenotype and AgingThe Biology of Mammalian Sir2 Homologs and their Role in L...The Chromophore Regeneration Pathway in Age-related Macula...The Genetic Role of Telomere Dynamics and DNA Damage Respo...The Molecular/Physiological Basis for Accelerated Aging in...The Rapid Identification of Hormones and Pharmacological C...The Role of P13K/Akt Dependent Phosphorylation of a Mammal...The Role of T-loops in Aging of Human CellsThe Role of the MORF/MRG Family of Novel Transcription Fac...The roles of recombination and telomerase in telomere main...Time Lapse Imaging of Neurons as They AgeToward a Comprehensive Assessment of Gene Expression durin...Use of Blood Stem Cells to Regenerate Neurons via the Tran... Select an institution Albert Einstein College of Medicine of Yeshiva University Baylor College of Medicine Boston Medical Center Brandeis University Buck Institute for Age Research Burnham Institute California Institute of Technology Center for Blood Research, Boston Children's Hospital, Boston Children's Hospital, Oakland Research Institute Dana Farber Cancer Institute Fred Hutchinson Cancer Research Center Harvard Medical School Harvard University J. David Gladstone Institutes Johns Hopkins University Lawrence Berkeley National Laboratory Massachusetts General Hospital Massachusetts General Hospital Cancer Center Massachusetts Institute of Technology Molecular Sciences Institute Purdue University Rockefeller University Scripps Research Institute Skirball Institute - New York University School of Medicine Southern Illinois University School of Medicine Stanford University Medical Center Stanford University School of Medicine University of California - Davis University of California - Irvine University of California - Los Angeles University of California - San Diego, Howard Hughes Medical Institute University of California - San Francisco University of California - San Francisco, UCSF Cancer Center University of Chicago University of Colorado - Boulder University of Connecticut Health Center University of Georgia University of Michigan University of North Carolina - Chapel Hill University of Southern California University of Texas Health Science Center - San Antonio University of Texas Southwest Medical Center University of Texas Southwestern Medical Center University of Washington Weill Medical College of Cornell University Whitehead Institute for Biomedical Research Yale University School of Medicine

Jochen Buck, M.D., Ph.D. Weill Medical College of Cornell University

Caloric restriction extends life-span in a wide variety of eukaryotic organisms from yeast to mammals. Cellular responses to nutritional availability are mediated by the cAMP signaling pathway in bacteria, cyanobacteria, and unicellular eukaryotes, and Dr. Guarente and co-workers demonstrated the glucose-activated cAMP-dependent protein kinase (PKA) pathway is directly linked to aging in budding yeast.

Together with Dr. Lonny Levin, our laboratory recently revealed the existence of a novel cAMP signaling cascade in mammals. In addition to the more widely studied source of cAMP, the hormonally-responsive, G protein-regulated, transmembrane adenylyl cyclases (tmACs), we identified a second cascade defined by an intracellular form of adenylyl cyclase, the soluble adenylyl cyclase (sAC). sAC seems to be ubiquitously expressed and is targeted to distinct subcellular locations within cells; i.e., nucleus, cytoskeleton, and mitochondria. sAC is not subject to regulation via G proteins, and its catalytic regions are more similar to cyanobacterial adenylyl cyclase (AC) catalytic domains than to other eukaryotic cyclases.

We recently demonstrated that, among mammalian cyclases, sAC is uniquely regulated by bicarbonate ions. Bicarbonate regulation of cyclase activity is conserved in cyanobacterial ACs suggesting an evolutionary conserved signaling pathway which senses bicarbonate. Intracellular carbonic anhydrases are present in all living organisms and instantaneously equilibrate cellular carbon dioxide and bicarbonate levels. Because energy metabolism (i.e., utilization of glucose and/or fatty acids to generate ATP) produces carbon dioxide, bicarbonate regulation of sAC and cAMP levels could provide an intrinsic mechanism for sensing the metabolic state of cells. While cellular responses to nutrient availability have long been known to be under hormonal control (i.e., glucagon) via modulation of tmACs and cAMP, we now propose that the cell also utilizes a signaling pathway originating from sAC-generated cAMP to intrinsically monitor its nutritional state.

Proposed research: Using a combination of biochemical, cellular and transgenic approaches, we propose to test the hypothesis that bicarbonate/carbon dioxide-regulated sAC acts as a nutritional sensor to monitor the metabolic state of mammalian cells, and to examine whether sAC is directly involved in aging via generation of the second messenger cAMP.

Contact Dr. Buck.