A New Protocol to Discover Novel Anti-Aging Compounds

Several natural and chemical compounds have been suggested to have effects as anti-aging drugs. For example, caloric restriction (CR) mimetics trans-resveratrol (Rsv) and 2-deoxy-D-glucose (2DG) are candidate compounds that can elongate life span of organisms, and they might also have roles in the regulation of telomere maintenance and mitochondrial functions. Recently, pharmaceutical medicaments rapamycin, an immunosuppressant and metformin, a medicine for diabetes, have been shown to act on the insulin/IGF1 signaling pathway. Therefore, they are also expected to have anti-aging effects. Here we propose a new protocol to discover novel compounds that can be used as a remedy to slow senescence and control aging in the aspect of promoter activities of telomere and energy metabolism-regulating factor encoding genes.

[1]  Andrzej Bartke,et al.  Growth hormone, insulin and aging: The benefits of endocrine defects , 2011, Experimental Gerontology.

[2]  G. Salles,et al.  Transcriptional Activation of hTERT, the Human Telomerase Reverse Transcriptase, by Nuclear Factor of Activated T Cells* , 2009, The Journal of Biological Chemistry.

[3]  Michael Chang,et al.  Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres , 2009, Genetics.

[4]  Bo O. Zhou,et al.  The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity , 2006, Nucleic acids research.

[5]  Laura Scott,et al.  Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome , 2003, Nature.

[6]  Y. Higami,et al.  The effect of resveratrol on the Werner syndrome RecQ helicase gene and telomerase activity. , 2011, Current aging science.

[7]  Eyal Gottlieb,et al.  TIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis , 2006, Cell.

[8]  Johan Auwerx,et al.  Sirtuins as regulators of metabolism and healthspan , 2012, Nature Reviews Molecular Cell Biology.

[9]  D. Sinclair,et al.  The role of nuclear architecture in genomic instability and ageing , 2007, Nature Reviews Molecular Cell Biology.

[10]  L. Mouchiroud,et al.  Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging , 2010, BioFactors.

[11]  F. Uchiumi,et al.  Effects of Thujaplicins on the Promoter Activities of the Human SIRT1 and Telomere Maintenance Factor Encoding Genes , 2012 .

[12]  T. Ikejima,et al.  The effect of 2‐deoxy‐d‐glucose on Werner syndrome RecQ helicase gene , 2009, FEBS letters.

[13]  F. Uchiumi,et al.  Effect of Lignin Glycosides Extracted from Pine Cones on the Human SIRT1 Promoter , 2013 .

[14]  M. Kupiec,et al.  Tor Complex 1 Controls Telomere Length by Affecting the Level of Ku , 2011, Current Biology.

[15]  Oksana Gavrilova,et al.  p53 Regulates Mitochondrial Respiration , 2006, Science.

[16]  C. Kenyon.  The genetics of ageing , 2010, Nature.

[17]  D. Sabatini,et al.  mTOR: from growth signal integration to cancer, diabetes and ageing , 2010, Nature Reviews Molecular Cell Biology.

[18]  C. Kahn,et al.  Endocrine regulation of ageing , 2007, Nature Reviews Molecular Cell Biology.

[19]  R. O'Sullivan,et al.  Telomeres: protecting chromosomes against genome instability , 2010, Nature Reviews Molecular Cell Biology.

[20]  H. Sakagami,et al.  Induction of antimicrobial activity by antitumor substances from pine cone extract of Pinus parviflora Sieb. et Zucc. , 1988, Anticancer research.

[21]  L. Chin,et al.  Telomere dysfunction induces metabolic and mitochondrial compromise , 2011, Nature.

[22]  K. Kitajima,et al.  Stimulation of Human Peripheral Blood Polymorphonuclear Cell Iodination by Lignin‐Related Substances , 1991, Journal of leukocyte biology.

[23]  Christina Yau,et al.  Ageing, oxidative stress and cancer: paradigms in parallax , 2008, Nature Reviews Cancer.

[24]  F. Uchiumi,et al.  Characterization of 5’-Flanking Regions of Various Human Telomere Maintenance Factor-Encoding Genes , 2011 .

[25]  T. Pandita,et al.  Human Heterochromatin Protein 1 Isoforms HP1Hsα and HP1Hsβ Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation , 2003, Molecular and Cellular Biology.

[26]  J. Stuart,et al.  Mitochondria, cellular stress resistance, somatic cell depletion and lifespan. , 2009, Current aging science.