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MARie CuRIe AGEing Network

Final Report Summary - MARRIAGE (MARie CuRIe AGEing Network)

One of achievements of developed societies has been the remarkable extension of human lifespan. In the upcoming decades the number of Europeans with advanced age will increase dramatically and age-associated diseases will become much more prevalent. Although a definite challenge to modern societies, our understanding of the mechanisms that contribute to ageing and its associated pathologies remain superficial and therapeutic or nutritional interventions unexplored. The complex nature of ageing as a scientific field calls thus for a multidisciplinary approach where teams of academic and industrial researchers join forces. That was the idea behind MARRIAGE.
The mail goal of MARRIAGE was to provide training in the field of biology of ageing to 11 Early Stage Researchers (ESRs) and 4 Experienced Researchers (ERs). For that, we have assembled a premier group of scientists whose research focuses on the molecular mechanisms that underlie ageing, with an emphasis on how maintenance of genomic integrity in self-renewing tissues is preserved under different metabolic rates. The key aim of the Network´s training program was thus the elucidation of the molecular pathway by which intrinsic genomic integrity can be modified by the extrinsic rate of metabolism.

MARRIAGE consisted of 10 beneficiaries and 2 associated partners, representing 7 Member states, Switzerland and Canada including 4 commercial enterprises and 15 fellows from 14 different nationalities. This heterogeneity has enriched not only the scientific exchange among Principle Investigators (PIs) and fellows but also the social interaction within the network. In terms of gender, 10 out of 15 fellows were female.

Multiple complementary training schemes have been implemented. These include specific research projects (including multiple academic and industrial secondments), and a variety of dedicated workshops organized by the academic and industrial partners of the Network. Because ESRs and ERs had access to a large variety of experimental approaches, techniques, and model systems, this Network constituted an optimal training environment for a next generation of scientists and will serve as an excellent preparation for the next steps in their academic, industrial, or governmental careers.

The main objective during the first two project years was to assure a successful start of the network. The latter translated into the enforcement of an effective management structure and communication strategy, including the creation of a Network’s website; the completion of recruitment; the starting of the fellow’s individual research projects and of training in line with the scientific aims and the training schedule described in the Grant Agreement ( Workpackages 1 and 2).

In the last 2 years, the network focused on the completion of its training program (Workpackage 2) and on the achievement of the goals set forward in the scientific workpackages (Workpackages 3 to 6).
In Workpackage 3: The role of DNA replication and repair in ageing, ESRs and ERs worked on the functional characterization of ageing tissues in progeroid model systems and developed and validated uniform assays that were used to compare various ageing phenotypes. As the ageing phenotypes studied were multi-faceted, the combined experience of the participating laboratories provided an excellent training platform for early stage researchers. Age-dependent alterations in cell signalling, proliferative responses and rates of mutagenesis were measured.
In Workpackage 4: The role of telomeres and cell senescence in ageing, ESRs and ERs worked in the field of telomere and cell senescence biology, using a variety of models and technological approaches to elucidate the molecular mechanism by which the RecQ family of DNA helicases plays roles in the suppression of telomere instability. Trainees in this Work Package assessed also the presence of senescent cells and molecularly characterized these cells in mouse models of accelerated ageing triggered by either DNA repair failure, or telomere uncapping, or mtDNA mutation.
In Workpackage 5: The role of stem cells in ageing the overall aim was to train ESRs and ERs in stem cell ageing, using a variety of different model systems and functional assays.
Students compared the genome-wide genetic and epigenetic status of young and aged hematopoietic stem cells. These cells were purified from regular strains of mice, but also purified stem cells from mice with a variety of progeroid phenotypes were also assayed.
Finally, in Workpackage 6: The role of metabolism and mitochondria in ageing, the overall aim was to train ESRs and ERs to use a variety of model systems and a range of technologies to investigate the involvement of metabolism and mitochondria in cellular and organismal ageing.
ESRs in this Workpackage exploited the unique advantages of C. elegans model system to dissect the role of cellular energy metabolism in ageing. Towards this aim, they combined molecular biology methodologies and state-of-the art optical imaging technologies with the power of genetic analysis in C. elegans.

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