Objective We pioneered an initially highly controversial connection between DNA damage and (accelerated) aging. In the previous ERC grant ‘DamAge’ we reached the stage that (segmental) aging in DNA repair-deficient mice can be largely controlled. The severity of the repair defect determines the rate of segmental aging; the repair pathways affected influence which organs age fast; conditional repair mutants allow targeting accelerated aging to any organ. Importantly, we found that dietary restriction (DR), the only universal intervention known to delay aging, extends remaining life- and healthspan in progeroid Ercc1Δ/- mutants by 200% (see Vermeij et al., Nature 2016 and fig.2). Also Xpg-/- progeroid repair mice strongly benefit from DR, generalizing this finding. The prominent Alzheimer- and Parkinson-like neurodegeneration is even retarded up to 30-fold(!) disclosing powerful untapped reserves unleashed by 30% less food, with enormous clinical potential. Also we discovered that in accelerated and normal aging gene expression declines due to accumulating stochastic transcription-blocking lesions and that DR counteracts genomic dysfunction. In Dam2Age we will focus on the cross-talk between DNA damage, aging and DR with emphasis on the relevance for normal aging, elucidate underlying mechanisms and use our unique -for DR research superior- mouse models and a variety of novel assays to search for effective nutritional-pharmacological DR mimetics. This serves as a stepping stone towards potent universal therapy for a range of repair-deficient progeroid syndromes and prevention of many aging-related diseases, most urgently dementia’s, to promote sustained health. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesgeneticsDNA Keywords Premature aging nutritional intervention dietary restriction progeroid syndromes mouse models DNA repair defects life-healthspan extension transcriptomics bioinformatics clinical translation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-ADG - ERC Advanced Grant Call for proposal ERC-2016-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Net EU contribution € 2 251 719,00 Address DR MOLEWATERPLEIN 40 3015 GD Rotterdam Netherlands See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 251 719,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Netherlands Net EU contribution € 2 251 719,00 Address DR MOLEWATERPLEIN 40 3015 GD Rotterdam See on map Region West-Nederland Zuid-Holland Groot-Rijnmond Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 251 719,00
