TY - JOUR
T1 - Age-related regulation of genes
T2 - Slow Dynamical Processes in Nature
AU - Kurachi, Kotoku
AU - Zhang, Kezhong
AU - Huo, Jeffrey
AU - Ameri, Afshin
AU - Kuwahara, Mitsuhiro
AU - Fontaine, Jean Marc
AU - Yamamoto, Kei
AU - Kurachi, Sumiko
N1 - Funding Information:
We thank Akiko Kurachi for her critical reading of the manuscript and Junko Ogura for her excellent help in manuscript preparation. This work was in part supported by grants to K.K. from the NIH (HL64522 and HL38644), the Multipurpose Arthritis Center of the University of Michigan (NIH 5-P60-AR-20557), the Michigan Diabetes Research and Training Center (NIH 5P60 DK20572) and the University of Michigan General Clinical Research Center (NIH MO1-RR-00042). K.Z., J.H. and M.K are recipients of the American Heart Association Postdoctoral Fellowship, the Howard Hughes Medical Institute Student Research Training Fellowship and the Uehara Memorial Foundation Fellowship, respectively.
PY - 2002/11/15
Y1 - 2002/11/15
N2 - Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named "age-dimension technology (ADT)". ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.
AB - Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named "age-dimension technology (ADT)". ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.
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U2 - 10.1016/S0378-4371(02)01250-5
DO - 10.1016/S0378-4371(02)01250-5
M3 - Conference article
AN - SCOPUS:0037112818
SN - 0378-4371
VL - 315
SP - 105
EP - 113
JO - Physica A: Statistical Mechanics and its Applications
JF - Physica A: Statistical Mechanics and its Applications
IS - 1-2
Y2 - 25 November 2001 through 27 November 2001
ER -