Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock.
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.
Kondratov
Roman V
RV
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA. kondrar@ccf.org
Kondratova
Anna A
AA
Gorbacheva
Victoria Y
VY
Vykhovanets
Olena V
OV
Antoch
Marina P
MP
D056930:ARNTL Transcription Factors; D000273:Adipose Tissue / Q000254:growth & development / Q000473:pathology; D000375:Aging / Q000235:genetics*; D019588:Aging, Premature / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D001835:Body Weight; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology; D009929:Organ Size / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D017382:Reactive Oxygen Species; C538961:Bmal1 protein, mouse