Dna Damage Response Is Essential for the Maintenance of Intestinal Homeostasis With Age

Abstract

Calorie restriction (CR) extends lifespan and delays the onset of a number of age-related diseases in multiple laboratory organisms. These anti-aging effects of CR may be mediated by increased lipid metabolism and oxidative stress resistance. Taurine (2-aminoethylphosphonic acid) is an amino acid that has been suggested to function as a regulator of both osmosis and lipid metabolism, and as an antioxidant. In this study, we aimed to evaluate the potential of taurine as a CR mimetic using rats and mice. Sprague Dawley (SD) rats were fed a diet supplemented with 0% (control), 0.5%, 1.0%, 3.0% or 5.0% (w/w) taurine for 2 weeks. SD rats fed a 5% taurine diet displayed a significant reduction in white adipose tissue mass compared with rats fed control diet (p < 0.05). Plasma and liver cholesterol and triglycerides were also significantly decreased in taurine-fed rats compared with controls (p < 0.05). Liver gene expression analysis showed decreased mRNA expression of fatty acid synthase and increased mRNA expression of carnitine palmitoyltransferase 1A, a key mediator of beta-oxidation (p < 0.05). Furthermore, C57BL/6 mice fed a 5% taurine diet for 16 weeks showed increased survival under the oxidative stress induced by injection of 3-nitropropionic acid versus mice fed control diet (p < 0.05). These results suggest that taurine might have CR-mimetic effects through modulation of lipid metabolism and induction of oxidative stress resistance. Kaohsiung, Taiwan, 6. Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan Introduction: Osteoporosis is characterized by loss of bone tissue while age is considered as the common risk factor. There is an impaired osteoblastic bone formation in comparison with osteoclastic bone resorption during aging. One of the possible cellular mechanisms of age-related bone loss is osteoblast senescence. MicroRNAs (miRNAs) regulate the expression of mRNA/protein targets and play an important part in cellular senescence. The purpose of this study was to investigate alternations in the miRNAs that are expressed in replicative senescence of human osteoblast cells. MICRORNA PROFILES OF IN VITRO CELLULAR SENESCENCE OF HUMAN OSTEOBLASTSMethods: Osteoblasts were grown in vitro and cultivated to the eighth generation cells. We then employed immunohistochemical techniques to identify the expression of senescence markers of senescence-associated β-galactosidase (SA-β-gal) activity. RNA isolation, small RNA library construction and deep sequencing were performed. The generated next-generation sequencing (NGS) data were analyzed using the miRSeq software package.Results: In vitro aging model showed the positive cell number of SA-β-gal stained osteoblasts were enhanced in the eighth generation senescent cells. Morphological changes of large, flat and multinucleated than earlier young cells (first generation cell as the control group) were observed. In the NGS profiles, 168 miRNAs demonstrated over 2-fold changes. For those read counts over 10 reads per million (RPM)...