title: Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice.
abstract: Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently it was demonstrated that BMAL1 deficiency results in premature aging in mice. Here we investigate the aging of mice deficient for CLOCK protein. Deficiency of the CLOCK protein significantly affects longevity: the average lifespan of Clock-/- mice is reduced by 15% compared with wild type mice, while maximum lifespan is reduced by more than 20%. CLOCK deficiency also results in the development of two age-specific pathologies in these mice, cataracts and dermatitis, at a much higher rate than in wild type mice. In contrast to BMAL1 deficient animals, Clock-/- mice do not develop a premature aging phenotype and do not develop the multiple age-associated pathologies characteristic of BMAL1 deficiency. Thus, although CLOCK and BMAL1 form a transcriptional complex, the physiological result of their deficiency is different. Our results suggest that CLOCK plays an important role in aging, specifically; CLOCK activity is critical for the regulation of normal physiology and aging of the lens and skin.
authors.affiliation: Department of Biological, Geological and Environmental Sciences and Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Yulia V
authors.initials: YV
authors.lastname: Dubrovsky
authors.forename: William E
authors.initials: WE
authors.lastname: Samsa
authors.forename: Roman V
authors.initials: RV
authors.lastname: Kondratov
mesh_terms: D056930:ARNTL Transcription Factors / Q000172:deficiency / Q000235:genetics; D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D056926:CLOCK Proteins / Q000172:deficiency* / Q000235:genetics; D002386:Cataract / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D057906:Circadian Clocks / Q000235:genetics; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D008136:Longevity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D015595:Skin Aging / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D056926:CLOCK Proteins; C538944:Clock protein, mouse