The Animal Research Facility of the National Institute of Public Health and Environment (RIVM, The Netherlands) has, in collaboration with the different research projects in this PPG, successfully conducted several longevity and cross sectional studies with mice having a defect in DNA repair and/or RNA transcription. Some of these mouse strains showed phenotypes of accelerated aging. As part of the present program renewal application the animal and pathology core will continue to conduct such studies, but will now have a more specific focus (based on the results obtained in the previous grant period) and will include intervention studies. On the basis of anticipated results of the 5 projects, intervention strategies will be developed in our mouse models, e.g. to eradicate senescent cells and to ameliorate ageing phenotypes through pharmaceutical and/or nutraceutical interventions. Overall, the specific aims of the animal/pathology core are: 1. To ensure uniformity and homogeneity of animals and the environment in which the animals will be housed;consequently the animals will be backcrossed into the same genetic C57BL/6JxFVB F1 hybrid background. 2. To ensure that the animals are raised in a pathogen free environment. 3. To facilitate the sharing of animals, tissues and cells among the individual investigators. 4. To conduct longevity and/or cross sectional studies with various single and double mutant or transgenic mouse models of interest to the consortium. 5. To conduct life-span intervention studies with short-lived progeroid mouse models, with one or two added cross sectional studies for the most promising interventions in mutant and wild type mice. To conduct full histopathology on all animals from the longevity studies and if necessary also on mice from the cross sectional studies. To make mutagenesis studies possible, all transgenic mouse lines will be crossed with lacZ containing pUR288 transgenic mice.

Public Health Relevance

The RIVM is the principal research institute of the Dutch government, and is proactive, through basic and applied research or in an advisory capacity, on all major areas of human health care and environmental protection. Acive participation within this consortium provides networking posibilities, access to and support for state-of-the-art aging research. These are considered prime conditions for the knowledgeable, credible and scientific advisory role of the RIVM. For that reason these activities are also suported by internal funds.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1)
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Albert Einstein College of Medicine
United States
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Hernandez-Segura, Alejandra; de Jong, Tristan V; Melov, Simon et al. (2017) Unmasking Transcriptional Heterogeneity in Senescent Cells. Curr Biol 27:2652-2660.e4
Milholland, Brandon; Suh, Yousin; Vijg, Jan (2017) Mutation and catastrophe in the aging genome. Exp Gerontol 94:34-40
Dong, Xiao; Zhang, Lei; Milholland, Brandon et al. (2017) Accurate identification of single-nucleotide variants in whole-genome-amplified single cells. Nat Methods 14:491-493
Vijg, Jan; Dong, Xiao; Zhang, Lei (2017) A high-fidelity method for genomic sequencing of single somatic cells reveals a very high mutational burden. Exp Biol Med (Maywood) 242:1318-1324
Baar, Marjolein P; Brandt, Renata M C; Putavet, Diana A et al. (2017) Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell 169:132-147.e16
Ogrodnik, Mikolaj; Miwa, Satomi; Tchkonia, Tamar et al. (2017) Cellular senescence drives age-dependent hepatic steatosis. Nat Commun 8:15691
Milholland, Brandon; Dong, Xiao; Zhang, Lei et al. (2017) Differences between germline and somatic mutation rates in humans and mice. Nat Commun 8:15183
Andriani, Grasiella A; Vijg, Jan; Montagna, Cristina (2017) Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain. Mech Ageing Dev 161:19-36
Lau, Cia-Hin; Suh, Yousin (2017) Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease. Gerontology 63:103-117
Perrott, Kevin M; Wiley, Christopher D; Desprez, Pierre-Yves et al. (2017) Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience 39:161-173

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