H2020Индивидуална стипендия2020–2022

EpiMetAgeing · Epitranscriptomics at the crossroads of metabolism and cellular ageing

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период
2020-09-15 → 2022-09-14
Финансиране от ЕС
160 932 €
Участници
1
Схема
MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Молекулярните механизми на стареенето при затлъстяване се изследват чрез анализа на регулатора TET2 и промените в РНК. Това помага да се разбере как метаболитните нарушения влияят върху функциите на клетките и как те могат да бъдат възстановени до младежко състояние.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Epitranscriptomics at the crossroads of metabolism and cellular ageing

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.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Ageing is an unavoidable consequence of living and constitutes the highest risk factor for most human diseases in modern “western” societies. Despise the frequently observed correlation between metabolic alterations and cellular ageing, the molecular mechanisms linking these two complex processes are far from being understood. Here the EpiMetAgeing project proposes to take a novel approach to investigate cell decline linked to obesity and ageing through the lenses of RNA modifications, specifically TET2-mediated 5-hydroxymethylation of cytosines (5hmC). For that purpose, we will characterize the impact of obesity throughout ageing in: (1) the distribution and dynamics of 5hmC epitranscriptomic modification and (2) the key RNA-binding proteins that mediate TET2 function. Given that RNA modifications are reversible, the ultimate goal of this project is to develop novel strategies for cellular rejuvenation. To this end the ER will use cutting-edge technologies, including next-generation sequencing techniques, proteomics, CRISPR activation and repression systems, metabolic phenotyping and iPSC technology. EpiMetAgeing will provide a deeper understanding of the implication of a specific RNA chemical modification in orchestrating metabolism and ageing. Our research has the potential to facilitate the identification of potential druggable targets for therapeutic intervention in age-associated metabolic diseases.EpiMetAgeing has been carefully designed by combining the ER and host expertise in a highly interdisciplinary research environment to boost her career opportunities, and enhance her possibilities to achieve a position of greater professional maturity and independence that will allow her transition to become a principal investigator in the European R&D system.

Оригинален текст от CORDIS (на английски).

Участници

  • UNIVERSIDAD DE SANTIAGO DE COMPOSTELA · Santiago De CompostelaКоординаторИспания

Връзки

Данни: CORDIS, © Европейски съюз