Project description
Rejuvenating blood to slow ageing
Ageing leads to the gradual decline of many cell types and organs, with the haematopoietic system particularly affected. Haematopoietic stem cells (HSCs) increasingly shift toward the myeloid lineage, weakening their ability to regenerate blood tissue and contributing to the build-up of senescent cells. Epigenetic reprogramming strategies using Yamanaka factors and c-Myc show potential for enhancing tissue regeneration, but it remains unclear how reprogramming one organ affects others and overall health. Supported by the Marie Skłodowska-Curie Actions programme, the REJUVIMMUNE project will develop new tools, including mRNA therapeutics and partial reprogramming mimicking cocktails (PRMCs), to target HSCs and study their effects on blood, immune function, and systemic ageing.
Objective
Aging is a complex process, encompassing the decline numerous cell types and organs. In this regard, recent progress suggests that the hematopoietic system is particularly influential; as we age, hematopoietic stem cells (HSCs) preferentially differentiate toward the myeloid lineage, thus losing their ability to regenerate fully functional blood tissue. Furthermore, a decline in the effector capacity of immune cells accounts for insufficient immunosurveillance of senescent cells, leading to their accumulation throughout the body.
From a therapeutic perspective, the hematopoietic system is particularly malleable to rejuvenating interventions. In recent years, strategies of epigenetic reprogramming achieved through the transient expression of the Yamanaka factors Oct4-Sox2-Klf4 (OSK) and the facultative expression of c-Myc -referred to as partial reprogramming- has progressively garnered attention for its potential application in regenerative medicine. Their capacity to transiently push fate-committed cells back to their developmental program and to remove epigenetic marks of damage enhances the capacity of tissues to regenerate after injury in several preclinical models. However, it is poorly understood whether single-organ partial reprogramming affects other tissues and health span, without risks for secondary transformation, undermining the translational potential for humans.
Across the REJUVIMMUNE project, I leverage on these limitations to develop unique tools –mRNA therapeutics and partial reprogramming mimicking cocktails (PRMCs)– for targeting partial reprogramming on HSCs (Objective 1) and elucidate cell intrinsic and extrinsic effects of OSK-rejuvenation on blood cells -including immune cells- and systemic aging, respectively (Objective 2).
In summary, the strategies proposed in this action hold great potential to counteract hematopoietic senescence and mitigating age-associated decline in organismal function, enhancing health span and organismal resilience.
Fields of science (EuroSciVoc)
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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171 77 STOCKHOLM
Sweden
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