Mitochondrial signaling, TOR, and life span

Abstract Growing evidence supports the concept that mitochondrial metabolism and reactive oxygen species (ROS) play a major role in aging and determination of an organism's life span. Cellular signaling pathways regulating mitochondrial activity, and hence the generation of ROS and retrograde signaling events originating in mitochondria, have recently moved into the spotlight in aging research. Involvement of the energy-sensing TOR pathway in both mitochondrial signaling and determination of life span has been shown in several studies. This brief review summarizes the recent progress on how mitochondrial signaling might contribute to the aging process with a particular emphasis on TOR signaling from invertebrates to humans.

[1]  B Chance,et al.  Hydroperoxide metabolism in mammalian organs. , 1979, Physiological reviews.

[2]  Wilhelm Haas,et al.  Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1 , 2005, Nature.

[3]  M. Zaidi,et al.  Mitochondria to nucleus stress signaling , 2003, Journal of Cell Biology.

[4]  Di Chen,et al.  The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span , 2004, Development.

[5]  D. Sabatini,et al.  Growing roles for the mTOR pathway. , 2005, Current opinion in cell biology.

[6]  R. Scarpulla,et al.  Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. , 2004, Genes & development.

[7]  Varshal K. Davé,et al.  Genome-wide responses to mitochondrial dysfunction. , 2001, Molecular biology of the cell.

[8]  P. Redman,et al.  Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer , 2004, Aging cell.

[9]  N. Avadhani,et al.  Mitochondrial signaling: the retrograde response. , 2004, Molecular cell.

[10]  D. Harman.  Aging: a theory based on free radical and radiation chemistry. , 1956, Journal of gerontology.

[11]  Matt Kaeberlein,et al.  Extension of chronological life span in yeast by decreased TOR pathway signaling. , 2006, Genes & development.

[12]  G. Fink,et al.  Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration , 2002, Nature.

[13]  T. Finkel,et al.  A role for mitochondria as potential regulators of cellular life span. , 2002, Biochemical and biophysical research communications.

[14]  Gary Ruvkun,et al.  A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity , 2003, Nature Genetics.

[15]  S. Jazwinski.  Yeast longevity and aging—the mitochondrial connection , 2005, Mechanisms of Ageing and Development.

[16]  Andrew G Fraser,et al.  Rates of Behavior and Aging Specified by Mitochondrial Function During Development , 2002, Science.

[17]  Benjamin R. Myers,et al.  FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Matt Kaeberlein,et al.  Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients , 2005, Science.

[19]  S. Nemoto,et al.  SIRT1 Functionally Interacts with the Metabolic Regulator and Transcriptional Coactivator PGC-1α* , 2005, Journal of Biological Chemistry.

[20]  M. Brand,et al.  Topology of Superoxide Production from Different Sites in the Mitochondrial Electron Transport Chain* , 2002, The Journal of Biological Chemistry.

[21]  J. Corton,et al.  Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  T. Johnson,et al.  A metabolic model for life span determination in Caenorhabditis elegans. , 2003, Developmental cell.

[23]  H. Nohl,et al.  Are mitochondria a permanent source of reactive oxygen species? , 2000, Biochimica et biophysica acta.

[24]  M. Brand.  Uncoupling to survive? The role of mitochondrial inefficiency in ageing , 2000, Experimental Gerontology.

[25]  K. Inoki,et al.  TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival , 2003, Cell.

[26]  V. Ferrans,et al.  Role for Mitochondrial Oxidants as Regulators of Cellular Metabolism , 2000, Molecular and Cellular Biology.

[27]  J. P. McCoy,et al.  The Mammalian Target of Rapamycin (mTOR) Pathway Regulates Mitochondrial Oxygen Consumption and Oxidative Capacity* , 2006, Journal of Biological Chemistry.

[28]  A. Jaeschke,et al.  Mammalian TOR: A Homeostatic ATP Sensor , 2001, Science.

[29]  S. Jazwinski,et al.  The retrograde response links metabolism with stress responses, chromatin-dependent gene activation, and genome stability in yeast aging. , 2005, Gene.

[30]  Robert S. Balaban,et al.  Mitochondria, Oxidants, and Aging , 2005, Cell.

[31]  S. Hekimi,et al.  Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. , 2001, Developmental cell.

[32]  D. Sabatini,et al.  mTOR Interacts with Raptor to Form a Nutrient-Sensitive Complex that Signals to the Cell Growth Machinery , 2002, Cell.

[33]  D. Wallace.  A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine , 2005, Annual review of genetics.

[34]  D. Kelly,et al.  PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. , 2006, The Journal of clinical investigation.

[35]  R. A. Butow,et al.  The mitochondrial genotype can influence nuclear gene expression in yeast. , 1987, Science.

[36]  D. Sabatini,et al.  Redox Regulation of the Nutrient-sensitive Raptor-mTOR Pathway and Complex* , 2005, Journal of Biological Chemistry.

[37]  L. Guarente,et al.  Calorie Restriction— the SIR2 Connection , 2005, Cell.

[38]  P. Silver,et al.  Elimination of replication block protein Fob1 extends the life span of yeast mother cells. , 1999, Molecular cell.

[39]  Tibor Vellai,et al.  Genetics: Influence of TOR kinase on lifespan in C. elegans , 2003, Nature.

[40]  S. Jazwinski,et al.  Interorganelle signaling is a determinant of longevity in Saccharomyces cerevisiae. , 1999, Genetics.

[41]  C. Kenyon.  The Plasticity of Aging: Insights from Long-Lived Mutants , 2005, Cell.

[42]  M. Hall,et al.  TOR Signaling in Growth and Metabolism , 2006, Cell.

[43]  B. Freedman,et al.  Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter‐organelle crosstalk , 1999, The EMBO journal.

[44]  N. Holbrook,et al.  Oxidants, oxidative stress and the biology of ageing , 2000, Nature.

[45]  S. Benzer,et al.  Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway , 2004, Current Biology.