Search

Author(s): Xiao Dong [1]; Brandon Milholland [1]; Jan Vijg (corresponding author) [1, 2] Driven by technological progress, human life expectancy has increased greatly since the nineteenth century. Demographic evidence has [...]

The extent of DNA repair was evaluated by measuring the removal of bezo(a)pyrene-induced DNA adducts in liver DNA of two parental strains, C57B1/6 and BALB/c, and three different chromosome 4 congenic mouse strains between one and three days after treatment.The removal of the main adduct in the two parental strains was at 86% for the C57B1/6 and 57% for the BALB/c, which was similar with the results in two of the congenic mouse strains, B6.C-H-16(sup c) and B6.C-H-26 (sup c). Removal forthe third mouse strain, B6,C-H-15 (sup c) was approximately 88%.

Introduction The ability of mammalian cells to remove DNA damage, induced as a consequence of the continuous exposure of cells to various endogenous and exogenous DNA-damaging agents, is of the [...]

The genetic basis of familial Alzheimer's disease may be rooted in deficient base excision repair in the brain as well as in fibroblast and lymphoid cells. The absence of efficient DNA repair causes accumulation of misrepaired or nonrepaired DNA damage and ultimately results inneuronal damage. The specific DNA damage in neuronal degeneration may be testedby measuring the amount of DNA lesions.

Author(s): Xiao Dong [1]; Brandon Milholland [1]; Jan Vijg (corresponding author) [1, 2] Replying to A. Lenart & J. W. Vaupel Nature 546, http://dx.doi.org/10.1038/nature22790 (2017) In the accompanying Comment [1], [...]

Abstract Background MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. Results We employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4 × 108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA. Conclusion Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.

In October 1989, EURAGE, the European Community's concerted action on aging and diseases, held a workshop on the molecular mechanisms of aging. It is believed that genes (which are comprised of DNA sequences and direct protein synthesis) affect aging and longevity in ways that are not yet understood. In the past decade, advances in biotechnology made it possible to perform DNA analysis much more easily, and facilitated progress in unravelling the aging process. Determining the reasons for the differences in life spans among species may enhance the identification of genes that are actually involved in aging. Aging might occur as a consequence of different gene activities, and may involve aging genes specific for an active aging process; deleterious genes that accumulate during life, eventually causing adverse effects; pleiotropic genes that may confer a short-term benefit, but a long-term risk; and longevity genes associated with a beneficial effect of a longer life span. Lower organisms, such as fungi, yeast, and fruit flies, have provided much information on the aging process. Another major research effort has involved the identification of candidate genes involved in intrinsic aging processes. These genes might affect the structural integrity or function of macromolecular structures, such as chromatin (which contains DNA, enzymes, and other components of protein synthesis) and membranes (which surround all cells and must be intact to protect the cell). Genetic studies of age-related pathology, such as diabetes and Alzheimer's type dementia, may also provide rewarding results. The effects of genes possibly involved with aging may be investigated by injecting them into mice; the technical difficulties of such experiments are discussed. Much research is needed before the regulation of longevity and aging can be understood, and the EURAGE workshop provided a clear rationale for future studies. (Consumer Summary produced by Reliance Medical Information, Inc.)

Abstract Background Systematic, high-throughput studies of mouse phenotypes have been hampered by the inability to analyze individual animal data from a multitude of sources in an integrated manner. Studies generally make comparisons at the level of genotype or treatment thereby excluding associations that may be subtle or involve compound phenotypes. Additionally, the lack of integrated, standardized ontologies and methodologies for data exchange has inhibited scientific collaboration and discovery. Results Here we introduce a Mouse Phenotype Analysis System (MPHASYS), a platform for integrating data generated by studies of mouse models of human biology and disease such as aging and cancer. This computational platform is designed to provide a standardized methodology for working with animal data; a framework for data entry, analysis and sharing; and ontologies and methodologies for ensuring accurate data capture. We describe the tools that currently comprise MPHASYS, primarily ones related to mouse pathology, and outline its use in a study of individual animal-specific patterns of multiple pathology in mice harboring a specific germline mutation in the DNA repair and transcription-specific gene Xpd. Conclusion MPHASYS is a system for analyzing multiple data types from individual animals. It provides a framework for developing data analysis applications, and tools for collecting and distributing high-quality data. The software is platform independent and freely available under an open-source license 1.