Due to the continuous increase in life expectancy in western societies, ageing has become the greatest risk factor for most human diseases such as cardiovascular and metabolic disorders, cancer and neurodegenerative processes. In turn, although obesity can affect an individual´s health at all stages of life, risk arising from metabolic disfunctions increases with age. In Europe the increasing prevalence of obesity and associated pathologies during ageing will translate in an Economic, Health and Social burden for the upcoming generations. Importantly, emerging evidence indicates that metabolism plays an important role in regulating epigenetic modifications that dramatically affect cellular function with age. It is widely known that ageing promotes the progressive loss of fitness of living organisms, but the causes of ageing remain one of the main open questions in Biology. Among the different approaches to erase cellular ageing hallmarks, somatic cell reprogramming with the Yamanaka factors has proven itself the best suited to rejuvenate cells, restoring a young phenotype. The EpiMetAgeing proposal aimed at dissecting novel molecular mechanisms whose deregulation contributed to ageing in an obesity context, and which could be reset to a youthful state through somatic cell reprogramming. In particular, we focused in dissecting the contribution of the epigenetic (i.e. acting on DNA) and epitranscriptomic (i.e. acting on RNA) regulator TET2, to cellular loss of fitness during ageing due to obesity. The EpiMetAgeing project aimed at scrutinizing the status quo and the dynamics of 5hmC in RNA in ageing and cellular rejuvenation, and dissecting TET2 interacting network which mediates this epitranscriptomic modification during ageing and rejuvenation in an obesity context. The appointment of the ER as a principal investigator in the Spanish R&D system has led to the early termination of the EpiMetAgeing proposal, but the exciting preliminary results obtained will be further explored in her new position as an independent researcher. For this reason, in the long run, the EpiMetAgeing project will contribute to expand the understanding of the molecular underpinnings of ageing, which is ultimately necessary to finally develop better strategies for alleviating or stopping age-related diseases in an obesity context.
