Projects

show Content ProExcellence Initiative

Aging-induced  impairments in organ regeneration and homeostasis (Acronym: RegenerAging) 

RegenerAging_NatureCellBiol_Fig3

Image: Consequences of DNA damage on clonal selection in tissue stem cells during ageing.
Nat Cell Biol. 2014 Mar;16(3):201-7. doi: 10.1038/ncb2928.

 

Facilitated by the association the research project "RegenerAging" was developed by the members of the Aging Research Center Jena (ARC). It is a close cooperation between the Leibniz Institute for Age Research – Fritz Lipmann Institute e.V. (FLI), the University Hospital Jena (UKJ) and Faculties of Medicine, Biology/Pharmacy and Mathematic/Computer Sciences of the Friedrich Schiller University Jena as well as the microscope developers of ZEISS Jena. The project is funded within the "ProExzellenz Initiative 2" of the State of Thuringia from 2015-19 with 3.9 million euros.

Clinical data and experimental studies show that aging leads to impairments in regeneration and tissue homeostasis. Molecular mechanisms that cause aging induced impairments in the functionality of stem cells and differentiated organ cells in regeneration and homeostasis remain currently not well understood. There is increasing evidence that alterations in signals controlling the regenerative capacity of differentiated cells but also the self-renewal and functionality of stem cells (e.g. Notch, Wnt, and CEBP-alpha signaling) contribute to aging associated defects in regeneration and tissue homeostasis. Aging associated accumulation of molecular damages represents another mechanism contributing to impairments of stem cells and differentiated cells in regeneration and tissue homeostasis. A variety of surveillance systems and checkpoints have evolved to counteract the accumulation of molecular damages (such as senescence, apoptosis, and autophagy), but it remains largely unknown, why these systems fail during aging. In addition to these cell intrinsic defects, there is experimental evidence that aging provokes alterations in the cell environment. That leads to impairments in cellular functions during regeneration and organ homeostasis including impairments of immune functions, the aberrant regulation of pro-inflammatory signals, the induction of epigenetic alterations, and the clonal selection of stem cells.
Together, imbalances in signaling pathways that control the functionality of stem cells and differentiated cells in regeneration, and tissue homeostasis vs. the activation of checkpoints and surveillance pathways that negate the accumulation of moleculardamages, influence the rate of tissue aging by impairing regeneration and organ homeostasis. The functional analysis of the underlying molecular mechanisms of these aging associated impairments is the main focus within the “ProExzellenz Initiative” which is funded by the State of Thuringia.

The research focuses on the following areas:

- Epigenetics of Aging
- Stem Cell Aging
- Immunology of Aging


RegenerAging will be instrumental to strengthen the research focus in key areas and key technologies to complement the existing expertise on aging research at the university campus in Jena. Specifically, we will focus on 3 funding lines:

- Recruitments of 3 “Tenure track groups”,
- Financing of 6 Ph.D. projects, and
- Development of a high-resolution microscopy