Journal Article

Exploring the uncharted role of cell senescence in rare diseases

Taci, Esi, Selvaggio, Piera, Barassi, Alessandra, Lesma, Elena, Massa, Valentina, Gervasini, Cristina, Di Fede, Elisabetta, Bernardelli, Clara

2025

Overview

Background Cellular senescence is a biological process in which the cell cycle is arrested in response to DNA damage caused by different endogenous and exogenous stimuli. In senescent cells, activation of intracellular cascade induces epigenetic, morphological and metabolic changes. Among them, senescent status is characterized by an alteration of the epigenome and the establishment of a peculiar senescence-associated secretory phenotype (SASP), which contributes to the extracellular matrix remodeling and senescence spreading. Growing interest is directed towards senescence relevance both in physiological processes and in pathological ones, including rare progeroid syndromes. However, little is known about senescence contribution to the onset and development of rare diseases in which aging traits are not manifested. Main body Here, we review the current knowledge about senescence involvement in four rare mendelian disorders of the epigenetic machinery (i.e. chromatinopathies) and four rare lung diseases, that can be considered a paradigm for understanding how epigenome alteration and aberrant microenvironment modification in senescence process might drive disease onset and progression. First, we report the main characteristics of chromatinopathies and the relation between the chromatin-related epigenetic defects and the senescence features in Sotos syndrome, Cornelia de Lange syndrome, Rett syndrome, and Kleefstra syndromes. Thereafter, we describe the pathological alteration and senescence involvement in cystic fibrosis, idiopathic pulmonary fibrosis, pulmonary arterial hypertension and lymphangioleiomyomatosis, considering them as models of rare lung diseases in which accumulation of senescent cells and their proinflammatory SASP have a central role. Conclusion Exploring the role of senescence in different and less common diseases might promote the understanding of the senescent process as a novel player in rare disorders, for a more comprehensive vision of their complexity and the suggestion of novel possible therapeutical targets.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Aging / Cells / Cellular Senescence - genetics / Cellular Senescence - physiology / Chromatin / Chromatinopaties / Cystic fibrosis / Development and progression / Diseases / DNA damage / Epigenesis, Genetic / Epigenetic inheritance / Epigenetics / Human Genetics / Humans / Lung diseases / Lung microenvironment / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Pharmacology/Toxicology / Physiological aspects / Pulmonary hypertension / Rare diseases / Rare Diseases - genetics / Rare Diseases - metabolism / Rare Diseases - pathology / Review / Senescence / Senescence-associated secretory phenotype