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)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Albert Einstein College of Medicine
United States
Zip Code
Han, Jeehae; Atzmon, Gil; Barzilai, Nir et al. (2015) Genetic variation in Sirtuin 1 (SIRT1) is associated with lipid profiles but not with longevity in Ashkenazi Jews. Transl Res 165:480-1
Raj, Divya D A; Jaarsma, Dick; Holtman, Inge R et al. (2014) Priming of microglia in a DNA-repair deficient model of accelerated aging. Neurobiol Aging 35:2147-60
Choi, Yong Jun; Li, Han; Son, Mi Young et al. (2014) Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair. PLoS One 9:e86358
Barnhoorn, Sander; Uittenboogaard, Lieneke M; Jaarsma, Dick et al. (2014) Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency. PLoS Genet 10:e1004686
Akman, Kemal; Haaf, Thomas; Gravina, Silvia et al. (2014) Genome-wide quantitative analysis of DNA methylation from bisulfite sequencing data. Bioinformatics 30:1933-4
Jung, Hwa Jin; Suh, Yousin (2014) Circulating miRNAs in ageing and ageing-related diseases. J Genet Genomics 41:465-72
Campisi, Judith; Robert, Ladislas (2014) Cell senescence: role in aging and age-related diseases. Interdiscip Top Gerontol 39:45-61
Derks, Kasper W J; Hoeijmakers, Jan H J; Pothof, Joris (2014) The DNA damage response: the omics era and its impact. DNA Repair (Amst) 19:214-20
Campisi, Judith (2014) Cell biology: The beginning of the end. Nature 505:35-6
Reiling, Erwin; Dollé, Martijn E T; Youssef, Sameh A et al. (2014) The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency. PLoS One 9:e93568

Showing the most recent 10 out of 155 publications