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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ARNTL Transcription Factors
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Adipose Tissue / growth & development
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Adipose Tissue / pathology
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Aging / genetics*
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Aging, Premature / genetics*
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Aging, Premature / physiopathology
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Animals
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Animals, Newborn
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Basic Helix-Loop-Helix Transcription Factors / genetics*
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Body Weight
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Circadian Rhythm / genetics*
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Female
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Gene Expression Regulation
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Muscle, Skeletal / pathology
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Organ Size / genetics
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Reactive Oxygen Species / metabolism
Substances
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ARNTL Transcription Factors
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Bmal1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Reactive Oxygen Species