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Genes & Dev. 20 (14): 1868-1873

Copyright © 2006 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock

Roman V. Kondratov1,4, Anna A. Kondratova2, Victoria Y. Gorbacheva1, Olena V. Vykhovanets1, and Marina P. Antoch1,3

1 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA;
2 Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA

Abstract: Mice deficient in the circadian transcription factor BMAL1 (brain and muscle ARNT-like protein) have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Here we report that Bmal1–/– mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. The early aging phenotype correlates with increased levels of reactive oxygen species in some tissues of the Bmal1–/– animals. These findings, together with data on CLOCK/BMAL1-dependent control of stress responses, may provide a mechanistic explanation for the early onset of age-related pathologies in the absence of BMAL1.

Key Words: BMAL1 • circadian clock • aging

Received for publication March 22, 2006. Accepted for publication May 9, 2006.

3 Corresponding authors.

E-MAIL antochm{at}ccf.org; FAX (216) 445-6269.

4 E-MAIL kondrar{at}ccf.org; FAX (216) 445-6269.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1432206

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