Innovating Works

MitoDNASen

Financiado
Investigating the regulation of the senescence-associated secretory phenotype (S...
Investigating the regulation of the senescence-associated secretory phenotype (SASP) by mitochondrial DNA (mtDNA) metabolism for the development of novel senotherapies. In response to various stresses such as DNA damage, telomere erosion, or oncogene activation, human cells can enter senescence. This process is characterized by irreversible proliferative arrest, deep transcriptional reprogramming... In response to various stresses such as DNA damage, telomere erosion, or oncogene activation, human cells can enter senescence. This process is characterized by irreversible proliferative arrest, deep transcriptional reprogramming, and expression of a collection of inflammatory factors termed the SASP (senescence-associated secretory phenotype). As it limits the proliferation of cells potentially bearing neoplastic potential, the triggering of cellular senescence is an essential tumor suppressing mechanism. However, the persistence and accumulation of senescent cells in aging and pathological contexts can have deleterious effects, particularly due to the SASP. It is thus fundamental to understand the basic physiology of senescent cells to develop so-called senomorphic drugs that modulate SASP expression. Changes in mitochondrial physiology elicited during cellular senescence onset strongly suggest that the maintenance and integrity of their mitochondrial DNA (mtDNA) may be altered. For instance, cytosolic leakage of mtDNA has been shown to take place in senescent cells and participate in SASP expression via immune pathways activation, but the contribution of mtDNA metabolism and replication in SASP expression has not yet been explored. My preliminary results show that mtDNA copy number increases continuously during senescence progression, accompanied by recomposing of the mitochondrial replisome. I also showed that this increase in mtDNA copy number promotes SASP expression. In the present project, I will characterize in details the alterations in mtDNA maintenance and integrity during senescence; profile the evolution of mitochondrial replisome composition; and characterize how the previous regulate SASP expression. The perspective of this project is to identify new senomorphic targets for controlling SASP expression and hereby alleviate the adverse effects of senescent cells in pathological contexts. ver más
19/09/2026
UMEA UNIVERSITET
207K€
Perfil tecnológico estimado
Duración del proyecto: 29 meses Fecha Inicio: 2024-03-25
Fecha Fin: 2026-09-19

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-03-25
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 207K€
Líder del proyecto
UMEA UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5