TY - JOUR
T1 - Heterochromatin islands and their dynamic reorganization
T2 - A hypothesis for three distinctive features of cellular aging
AU - Imai, Shin Ichiro
AU - Kitano, Hiroaki
N1 - Funding Information:
Acknowledgments—We thank Brad Johnson, Robert A. Marciniak, Minoru S.H. Ko, Toshiya Takano, and Tadahiro Fujino for discussion and critical reading of this manuscript. S.I. was supported by the Grant-in-Aids for Scientific Research from the Ministry of Education, Science, Sports, and Culture in Japan, and Keio University Sakaguchi-Memorial Medical Science Fund.
PY - 1998/9
Y1 - 1998/9
N2 - The mechanism of cellular aging has been suggested to play an important role in organismic aging, but the molecular linkage between them is not still understood. The recent progress in the studies of telomere and telomerase demonstrates their substantial roles in the mechanism of cellular aging. On the other hand, these studies also raise controversial issues about the generality of the telomere hypothesis. The heterochronic, polymorphic, and probabilistic features of cellular aging should be reconsidered critically. In this review, we attempt to develop a general scheme for the driving force of cellular aging, based on our molecular and computational studies. Our molecular analyses suggest that global transcriptional repressive structures are essentially involved in cellular aging-associated transcriptional regulation. From our theoretical studies, systematic reorganization of these repressive structures are suggested to be a fundamental driving force of cellular aging. The heterochromatin island hypothesis is proposed to give a rational explanation for the three distinctive features of cellular aging. The importance of a dynamic equilibrium in heterochromatin islands is also discussed for cellular and organismic aging.
AB - The mechanism of cellular aging has been suggested to play an important role in organismic aging, but the molecular linkage between them is not still understood. The recent progress in the studies of telomere and telomerase demonstrates their substantial roles in the mechanism of cellular aging. On the other hand, these studies also raise controversial issues about the generality of the telomere hypothesis. The heterochronic, polymorphic, and probabilistic features of cellular aging should be reconsidered critically. In this review, we attempt to develop a general scheme for the driving force of cellular aging, based on our molecular and computational studies. Our molecular analyses suggest that global transcriptional repressive structures are essentially involved in cellular aging-associated transcriptional regulation. From our theoretical studies, systematic reorganization of these repressive structures are suggested to be a fundamental driving force of cellular aging. The heterochromatin island hypothesis is proposed to give a rational explanation for the three distinctive features of cellular aging. The importance of a dynamic equilibrium in heterochromatin islands is also discussed for cellular and organismic aging.
KW - Cellular aging
KW - Heterochromatin islands
UR - http://www.scopus.com/inward/record.url?scp=0032162220&partnerID=8YFLogxK
M3 - Review article
C2 - 9789733
AN - SCOPUS:0032162220
VL - 33
SP - 555
EP - 570
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
IS - 6
ER -