Back to Search
Start Over
Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice.
- Source :
-
Aging cell [Aging Cell] 2014 Aug; Vol. 13 (4), pp. 709-18. Date of Electronic Publication: 2014 May 06. - Publication Year :
- 2014
-
Abstract
- The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2 mg kg(-1) day(-1) ) was administered orally for 5 months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated β-galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the IκBα and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound.<br /> (© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
- Subjects :
- Aging drug effects
Aging pathology
Animals
Fatty Acids administration & dosage
Fatty Liver complications
Fatty Liver drug therapy
Glucose Intolerance complications
Glucose Intolerance pathology
Inflammation complications
Inflammation drug therapy
Insulin metabolism
Lipid Metabolism drug effects
Lipopolysaccharides
Liver drug effects
Male
Mice, Inbred C57BL
NF-kappa B metabolism
Oxidative Stress drug effects
Pheromones administration & dosage
Phosphorylation drug effects
Survival Analysis
beta-Galactosidase metabolism
Fatty Acids pharmacology
Fatty Liver pathology
Feeding Behavior drug effects
Inflammation pathology
Liver pathology
Pheromones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1474-9726
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Aging cell
- Publication Type :
- Academic Journal
- Accession number :
- 24796965
- Full Text :
- https://doi.org/10.1111/acel.12224