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(Circulation Research. 2006;98:450.)
© 2006 American Heart Association, Inc.

Editorials

How Senescent Vascular Cells Lose Their Clock Age-Dependent Impairment of Circadian Rhythmicity in Smooth Muscle Cells

Barbara Illi, Carlo Gaetano, Maurizio C. Capogrossi

From the Laboratorio di Biologia Vascolare e Terapia Genica (B.I.), Centro Cardiologico Fondazione "I. Monzino", IRCCS, Milan; and the Laboratorio di Patologia Vascolare (C.G., M.C.C.), Istituto Dermopatico dell’ Immacolata, IRCCS, Rome, Italy.

Correspondence to Dr Maurizio C. Capogrossi, Direttore del Laboratorio di Patologia Vascolare, Istituto Dermopatico dell’Immacolata, Via dei Monti di Creta 104, 00167 Rome, Italy. E-mail capogrossi@idi.it

See related article, pages 532–539

Key Words: senescence • gene expression • chromatin • circadian rhythm • cardiovascular

An extract of the first 250 words of the full text is provided, because this article has no abstract.

"Oh dear! Oh dear! I shall be too late!"

— —Alice’s Adventures in Wonderland, Lewis Carroll

In mammals, as well as in flies and even in prokaryotes, circadian rhythmicity is allowed by a genetic clockwork that tightly regulates organisms’ adaptation to daily variations of light, temperature, and other living conditions.¹ The master pacemaker of the hierarchically organized cell-autonomous circadian clocks² is localized in the densely packed 2x10⁴ neurons of the hypothalamic suprachiasmatic nuclei (SCN), which is reset mainly by light signals captured by the retina. Although clocks resident in peripheral tissues, the so-called peripheral clocks, are mainly controlled by the SCN, an abrupt change in feeding time synchronizes these clocks independently of the central clock.³ In fact exogenous (eg, light) or endogenous rhythms can temporally adjust the cellular clocks, whose main characteristics are (1) feedback regulation and (2) 24 hours oscillatory period.

At molecular level, circadian rhythms are maintained by the intracellular feedback loop of the clock genes.⁴ The principal members of this family are the mPer 1 and 2 genes,⁵ Brain and Muscle RNA-t-like protein (BMAL-1),⁶ Clock,⁷ the 2 Cryptochrome genes (mCry1 and 2),⁸ Casein Kinase I (CKI),⁹ and the orphan receptor Rev-erb.¹⁰ These genes constitute a well-conserved transcritpion/translation-based negative feedback loop. In mammals, Clock and BMAL-1 proteins are in the positive limb of the loop, whereas mPERs and Cryptochromes are in the negative.^2,11 Clock/BMAL-1 heterodimeric complex, associated to the histone acetyltransferase p300,¹² bind to an E-box motif in . . . [Full Text of this Article]

Related Article:

Cellular Senescence Impairs Circadian Expression of Clock Genes In Vitro and In Vivo

Takeshige Kunieda, Tohru Minamino, Taro Katsuno, Kaoru Tateno, Jun-ichiro Nishi, Hideyuki Miyauchi, Masayuki Orimo, Sho Okada, and Issei Komuro
Circ. Res. 2006 98: 532-539. [Abstract] [Full Text] [PDF]