Periodic Reporting for period 1 - HealthAge (Joint Training and Research Program on Lifespan Regulation Mechanisms in Health and Disease)
Berichtszeitraum: 2019-05-01 bis 2021-04-30
Ageing is an inexorable homeostatic failure of complex but largely unknown aetiology that leads to increased vulnerability to disease (e.g. cancer, diabetes, musculoskeletal and cardiovascular diseases, immune-senescence neurodegeneration) with enormous consequences on the quality of individual lives and the overall cost to society. Human efforts over the last centuries have succeeded in substantially lengthening lifespan, allowing ageing to become a common feature of western societies. It has been, however, significantly challenging to unravel the molecular basis of the processes that cause loss of bodily functions and degeneration of cells and tissues with advancing age. The discouraging complexity of the ageing process, the noticeable lack of tools to study it, and a shortage of experimentally tractable model systems have greatly hindered any testable hypothesis-driven approaches to understand the molecular basis of ageing, particularly in mammals. It is now widely accepted that ageing is evolved by limitations in somatic maintenance, resulting in the gradual build-up of indiscriminate macromolecular damage accumulation, stem cell exhaustion, deregulated nutrient sensing, metabolic, epigenetic and structural changes as well as loss of proteostasis and altered intercellular communication (Figure 1). However, an accumulating body of evidence also suggests that ageing is subject to regulation by evolutionarily highly conserved molecular pathways. Thus, macromolecular damage may drive the functional decline with ageing; however, a battery of longevity assurance mechanisms may set the pace on how rapidly damage builds up and function is lost over time. For instance, calorie restriction (CR) is likely the best characterized and most reproducible strategy for extending lifespan (Figure 2). Studies in several model organisms i.e. S. cerevisiae, C. elegans, D. melanogaster, M. musculus, non-human primates and in human cell lines have revealed a number of longevity assurance pathways that impinge on biological processes involved in growth and energy metabolism. These signalling circuits aim at surmounting an adaptive response that promotes somatic maintenance, cellular fitness and longevity via activation of e.g. autophagy, the natural process that disassembles unnecessary or dysfunctional components, including damaged mitochondria, stress defense mechanisms, and survival pathways while attenuating pro-inflammatory mediators, cellular growth and senescence. However, at present it remains unknown such signalling circuits are functionally in longevity assurance mechanisms, how they are connected to health and disease and how any putative targets can be exploited for the development of rationalized intervention strategies to combat age-related diseases, including cancer.
To address this central thematic area, HealthAge was carefully designed to create a joint European program of excellence in training and research in the field of lifespan regulation mechanisms in development and diseases. By integrating research from basic mechanisms to translational research applications, HealthAge combines top-level, state-of-the-art and interdisciplinary research skills to tackle a series of relatively short-term research aims that are achievable within the time course of the Action.
The research aims are centred to 15 ESRs and are structured into three functionally-linked thematic areas (Figure 3):
i. Functional insights into lifespan regulation mechanisms (WP4).
ii. Longevity assurance pathways in development and disease (WP5).
iii. Novel approaches against age-related diseases and progeria (WP6)
To address this central thematic area, HealthAge was carefully designed to create a joint European program of excellence in training and research in the field of lifespan regulation mechanisms in development and diseases. By integrating research from basic mechanisms to translational research applications, HealthAge combines top-level, state-of-the-art and interdisciplinary research skills to tackle a series of relatively short-term research aims that are achievable within the time course of the Action.
The research aims are centred to 15 ESRs and are structured into three functionally-linked thematic areas (Figure 3):
i. Functional insights into lifespan regulation mechanisms (WP4).
ii. Longevity assurance pathways in development and disease (WP5).
iii. Novel approaches against age-related diseases and progeria (WP6)
The HealthAge ITN Program started its activities on May 1, 2019. Overall, the HealthAge program is on schedule and has met its main objectives as set out in the original workplan. There have been no changes in the objective of the research, the current state of the art (in relation to the network), the research methodology and approach and the originality or innovative aspects of the relevant ESR projects and the network.
All ESRs have been recruited by the participating labs and the research and training plans have been drafted and submitted. So far, attention has been given towards defining the overall research directions to current research trends in the respective field, set up and optimize the relevant assays needed as well as prepare and test the experimental animal or cell culture models for their suitability with respect to the particular project questions.
Despite the rather challenging obstacle of the SARS-Cov-2 epidemic, there are no outstanding issues with the overall implementation of the program until now. The deliverables have been completed and milestones for this period have been met. The HealthAge website and data management plan are in place, training courses have begun and the outreach strategy of the Network has enhanced the overall exposure of the program.
All ESRs have been recruited by the participating labs and the research and training plans have been drafted and submitted. So far, attention has been given towards defining the overall research directions to current research trends in the respective field, set up and optimize the relevant assays needed as well as prepare and test the experimental animal or cell culture models for their suitability with respect to the particular project questions.
Despite the rather challenging obstacle of the SARS-Cov-2 epidemic, there are no outstanding issues with the overall implementation of the program until now. The deliverables have been completed and milestones for this period have been met. The HealthAge website and data management plan are in place, training courses have begun and the outreach strategy of the Network has enhanced the overall exposure of the program.
HealthAge is designed as a multilayered approach to develop knowledge on longevity assurance pathways and their therapeutic use for a wide range of debilitating diseases associated with old age. HealthAge brings in leading experts with proven excellence in the proposed research topic and state-of-the art tools and model organisms that span the entire spectrum of ageing research ranging from fundamental concepts to therapeutic approaches aiming at combating age-related organismal decline. Indeed, we foresee that HealthAge will translate into new knowledge and the development of rationalized intervention strategies to combat age-related diseases.
The complete HealthAge training program will enable ESRs to develop and a solid scientific basis, critical judgment and discipline in their research activities allowing them to reach scientific maturity and independence. Also, the combination of basic biology and cutting-edge technologies of the training program will ensure that the fellows will graduate as a new breed of scientists trained in facing the challenges of contemporary post-genomic biology using advanced technological tools that are widely applicable in both academia and industry, thereby substantially enhancing their research career prospects. The successful outcomes of both research and training dimensions of HealthAge enhances the competitiveness of the participating labs by increasing the number of researchers that will be interested to join them, even beyond the lifetime of HealthAge, and of Europe in general through the generation of highly trained young researchers and through the diffusion/exploitation of proprietary knowledge.
The European Research area, as a result has benefited greatly, as this action has allowed interaction between ESRs and respective labs and has revealed opportunities of cooperation between institutions within the EU as well as the wider international arena. Moreover, HealthAge brings together the students, academic institutions with the industry, increasing the overall quality of academic and industrial training of ESRs. HealthAge also strengthens the European human potential in research, contributes to the European Research Base and to EU’s blueprint for sustainable and inclusive growth.
The complete HealthAge training program will enable ESRs to develop and a solid scientific basis, critical judgment and discipline in their research activities allowing them to reach scientific maturity and independence. Also, the combination of basic biology and cutting-edge technologies of the training program will ensure that the fellows will graduate as a new breed of scientists trained in facing the challenges of contemporary post-genomic biology using advanced technological tools that are widely applicable in both academia and industry, thereby substantially enhancing their research career prospects. The successful outcomes of both research and training dimensions of HealthAge enhances the competitiveness of the participating labs by increasing the number of researchers that will be interested to join them, even beyond the lifetime of HealthAge, and of Europe in general through the generation of highly trained young researchers and through the diffusion/exploitation of proprietary knowledge.
The European Research area, as a result has benefited greatly, as this action has allowed interaction between ESRs and respective labs and has revealed opportunities of cooperation between institutions within the EU as well as the wider international arena. Moreover, HealthAge brings together the students, academic institutions with the industry, increasing the overall quality of academic and industrial training of ESRs. HealthAge also strengthens the European human potential in research, contributes to the European Research Base and to EU’s blueprint for sustainable and inclusive growth.