Project description
Telomeric-based treatment to reduce immunosenescence
Immunosenescence refers to the decline in immune function due to shrinking lymphoid organs, reduced immune diversity, and chronic inflammation, all of which impair vaccine responses in older individuals. Telomere dysfunction plays a role in this process by generating non-coding RNAs that trigger DNA damage responses, leading to cellular senescence. Telomerase-deficient (Terc-/-) mouse models exhibit many characteristics of immunosenescence. Treatment with telomeric antisense oligonucleotides (tASOs) has shown promise in reducing immunosenescence and inflammation. The ERC-funded TELOVACCINE project aims to test the effectiveness of tASOs in rejuvenating the immune system of aged wild-type (WT) mice, a more natural model of ageing. The project will assess whether this treatment can improve immune responses, including vaccine efficacy, in older populations.
Objective
The immune system is remodeled with age, going through a series of changes known as “immunosenescence’, including the involution of primary lymphoid organs, the contraction of the immune repertoire, a progressive lineage skewing towards the myeloid lineage and a low-grade pro-inflammatory status. A consequence of immunosenescence impacting the morbidity and mortality of infectious diseases is a dramatically reduced vaccine response in the elderly. Thus, reducing the burden of immunosenescence has the potential to impact the effectiveness of vaccine response.
An established hallmark and driver of age-associated functional decline is telomere dysfunction. Dysfunctional telomeres are actively transcribed to generate telomeric non-coding RNAs (tncRNA) which are essential to recruit DNA Damage Response (DDR) factors at damaged telomeres, thus fueling DDR and causing cellular senescence initiation and maintenance. Sequence-specific telomeric antisense oligonucleotides (tASOs) target these tncRNAs and effectively inhibit DDR activation, ameliorating age-related phenotypes in mouse models.
The telomerase-deficient (Terc-/-) mouse model, causes telomere shortening and dysfunction, recapitulating features of immunosenescence: immune system reactivity reduction, decreased long term renewal of hematopoietic stem cells and lymphocytes numbers, increased neutrophil count. tASOs treatment has beneficial long-term effect in this model, by decreasing immunosenescence and counteracting inflammation. We now plan to test the efficacy of tASOs treatment on ‘rejuvenating’ the immune system of aged wild type mice, a ‘physiological’ setting for aging. The final goal will be to assess if tASOs impact on vaccine response in both models: young Terc-/- mice and aged WT mice. In summary, we plan to determine the efficacy of tASOs to improve immune responses, including vaccines, in the elderly.
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.
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.
- social sciences sociology demography mortality
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences genetics RNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-POC2
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20139 Milano
Italy
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