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Macrophage aging and rejuvenation

Objective

Tissue resident macrophages are essentially present in every organ of the body and perform critical functions in immunity,
tissue homeostasis and regeneration. Recent evidence shows that resident macrophages can originate from embryonic
progenitors and be maintained in tissues long term by local proliferation independently of monocytes. This self-renewal
ability, however, appears to decline with age, with potentially major consequences for the response to infection, the
resolution of inflammation and the ability for tissue regeneration. Understanding the decline of self-renewal in the aging
macrophage may thus hold key elements for maintaining healthy tissue integrity. Drawing from analogies to stem cell self-renewal we want to decipher the molecular and cellular parameters of macrophage self-renewal and its decline with age.
We want to understand the age-associated changes in gene expression and epigenetic identity of tissue macrophage
populations with the ultimate goal to reverse age dependent decline in self-renewal and function. Results from my
laboratory have identified transcription factors that control the access to a network of self-renewal genes that are also used in stem cells. Using several complementary genetic mouse models tapping into this network we want to investigate whether its activation in resident macrophage population in vivo can rejuvenate their self-renewal capacity and revert aging related changes. These approaches will be complemented by unbiased genome wide screens in vivo using latest generation CRISPR/Cas9 genome editing technology to identify new signaling pathways guiding macrophage self-renewal and aging. Using innovate combinations of genetics and adoptive transfer protocols we will test whether this knowledge can be employed to reverse macrophage dependent loss of immune competence and failed tissue regeneration with age. Our results will lead to new general insight and potential novel cellular therapies for degenerative diseases.

Fields of science (EuroSciVoc)

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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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.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

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

(opens in new window) ERC-2015-AdG

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Host institution

TECHNISCHE UNIVERSITAET DRESDEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 352 846,78
Address
HELMHOLTZSTRASSE 10
01069 Dresden
Germany

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Region
Sachsen Dresden Dresden, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 352 846,78

Beneficiaries (2)

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