Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1.
Deficiency of the circadian clock protein BMAL1 leads to premature aging and increased levels of reactivate oxygen species in several tissues of mice. In order to investigate the role of oxidative stress in accelerated aging and development of age-related pathologies, we continuously administered the antioxidant N-acetyl-L-cysteine toBmal1-deficient mice through their entire lifespan by supplementing drinking water. We found that the life long treatment with antioxidant significantly increased average and maximal lifespan and reduced the rate of age-dependent weight loss and development of cataracts. At the same time, it had no effect on time of onset and severity of other age-related pathologies characteristic of Bmal1-/- mice, such as joint ossification, reduced hair regrowth and sarcopenia. We conclude that chronic oxidative stress affects longevity and contributes to the development of at least some age-associated pathology, although ROS-independent mechanisms may also play a role. Our bioinformatics analysis identified the presence of a conservative E box element in the promoter regions of several genes encoding major antioxidant enzymes. We speculate that BMAL1 controls antioxidant defense by regulating the expression of major antioxidant enzymes.
Kondratov
Roman V
RV
Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA. r_kondratov@csu.ohio.edu
Vykhovanets
Olena
O
Kondratova
Anna A
AA
Antoch
Marina P
MP
D056930:ARNTL Transcription Factors / Q000235:genetics / Q000502:physiology*; D000111:Acetylcysteine / Q000494:pharmacology*; D019588:Aging, Premature / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001168:Arthritis / Q000235:genetics / Q000517:prevention & control; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000235:genetics; D002386:Cataract / Q000235:genetics / Q000517:prevention & control; D024721:E-Box Elements / Q000502:physiology; D005979:Glutathione Peroxidase / Q000235:genetics; D006801:Humans; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009999:Ossification, Heterotopic / Q000235:genetics / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D002679:Pan troglodytes; D054464:Peroxiredoxins / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
D056930:ARNTL Transcription Factors; D000975:Antioxidants; C538961:Bmal1 protein, mouse; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000111:Acetylcysteine