Project description:<p>Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice were indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To functionally prove that the young and old microbiome impacts differently on the bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.</p>
Project description:Naïve T cells (CD4+CD62LhiCD44loCD25-) were purified from spleens of young (2 months; n=3) and aged (22 months; n=3 pools of five mice) mice and were either frozen or activated for 24 hrs.
Project description:Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigated the methylation trajectories in DNA from 82 male mouse (C57BL/6J/Ukj) colons at five different time points (3, 9, 15, 24, 28 months). Our study indicates the existence of linear and nonlinear DNA methylation changes during aging. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 mo) and mid-to-late-life (15-24 mo) transitions, separating the rodents' life into three major stages. The results were validated with samples from an independent mouse cohort of 20 male C57BL6/J mice at four different ages (3, 7, 12, 27 months).
Project description:To identify molecular changes underlying the chemopreventive or tumor promoting effects of SRD5A inhibition, we profiled gene expression changes in benign prostate epithelium from patients with PCa treated with dutasteride, a dual SRD5A inhibitor. Subjects were aged 45-80 years with clinically localized PCa (T1C to T2b), Gleason score <7, and serum PSA 2.5-10 ng/dL. 81 men were randomized to immediate RP (n=25) or to dutasterdie at 0.5 mg (n=26) or 3.5 mg (n=24) orally per day for four months prior to RP. Prostate samples embedded in OCT were used for laser capture microdissection (LCM). Keywords: clinical trial, Dutasteride, PEDB, dose response, prostate cancer, microarray