Longevity and aging associated genes that control self-renewal and function of adult stem cells during aging

Objective

Adult stem cells are essential for the lifelong maintenance and regeneration of various organs and tissues. Experimental and clinical data indicate that the functional capacity of adult stem cells in organ regeneration declines during aging. Molecular mechanisms that cause impairments in stem cell function during aging remain to be delineated. Genetic analyses identified a growing number of genes and genetic loci that are associated with longevity and aging in model organisms and humans. For most of these associations the molecular mechanisms and its functional relevance for mammalian aging remain unknown. In many cases of genetic loci associations, the responsible genes have not even been identified. A bottleneck in our understanding of aging remains to identify functionally relevant genes and molecular mechanisms from this growing list of genetic association with aging. Emerging experimental data indicate that aging/longevity-associated genes influence the functional reserve of adult stem cells. Here, I propose to develop and lead a research program analyzing longevity and aging associated genes and gene loci by reverse genetic approaches. In vivo and ex vivo RNAi will identify genes and molecular mechanisms that affect the function of stem cells in aging mice or genetically engineered mice modeling accelerated accumulation of molecular damages and stem cell dysfunction. Analysis of primary human stem cells from young vs. old donors will delineate whether the identified genes and mechanisms are conserved in humans. Reverse genetic approaches of aging/longevity-associated genes have not been conducted in adult mammalian stem cells. Our group gained significant expertise in analyzing molecular mechanisms of stem cell maintenance and function as well as in conducting RNAi screens in different murine stem cell compartments. Our studies will delineate novel mechanisms of stem cell aging and its implication for defects in organ homeostasis and regeneration during aging.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• medical and health sciences medical biotechnology cells technologies stem cells
• medical and health sciences basic medicine physiology homeostasis

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2012-ADG_20120314
See other projects for this call

Funding Scheme

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ERC-AG - ERC Advanced Grant

Host institution

Beneficiaries (1)