HealthAge · Joint Training and Research Program on Lifespan Regulation Mechanisms in Health and Disease

Joint Training and Research Program on Lifespan Regulation Mechanisms in Health and Disease

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)

Data: CORDIS, © European Union