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immSC-AgingFate

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The Interplay of Aging, Immune Signaling and Stem Cell Function
Adult stem cells (SCs) sustain tissue renewal and repair throughout life. The SC niche is fundamental in the regulation of SC function and an important contributor to SC decline in aging. While alterations in the tissue’s immune e... Adult stem cells (SCs) sustain tissue renewal and repair throughout life. The SC niche is fundamental in the regulation of SC function and an important contributor to SC decline in aging. While alterations in the tissue’s immune environment are emerging as important contributors to impairments found in aged organs, their contribution to SC dysfunction in aging is unknown. The skeletal muscle (SkM) is a paradigmatic model to study age-related loss of repair capacity. Muscle stem cell (MuSC) function during regeneration requires plasticity in transit between states of quiescence, activation and differentiation. MuSC functional impairments in aging result from changes in the extrinsic cues that govern their behavior, but also cell intrinsic alterations, including senescence and defects in lineage commitment. However, we still have a limited understanding of how changes in the environment manifest as SC intrinsic defects. Our previous work indicates that changes in immune signaling are important drivers of MuSC dysfunction and regenerative decline in aging. Here, we propose to identify the contribution of specific immune populations and signals to changes in regenerative capacity and MuSC activity in aging (Aim 1). We hypothesize that the immune environment is an essential regulator of MuSC plasticity and lineage commitment under regenerative pressure, and immune alterations underlie defects in MuSC lineage fidelity in aging. We propose to map the trajectories of MuSCs diverging from the myogenic lineage and uncover the changes in epigenetic landscape that underlie the loss of lineage fidelity associated with immune aging, identifying transcriptional regulators of MuSC fate (Aim 2). The knowledge generated on the mechanisms linking immune aging and MuSC dysfunction will be tested for the conservation in human SkM and will be applied to improve the success of MuSC-based therapies in aging (Aim 3). ver más
28/02/2029
iMM
2M€
Perfil tecnológico estimado
Duración del proyecto: 60 meses Fecha Inicio: 2024-01-29
Fecha Fin: 2029-02-28

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-01-29
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2023-COG: ERC CONSOLIDATOR GRANTS
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANT... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5