Cellular senescence in ageing and neurodegenerative disorders: Molecular mechanisms, biomarkers, and therapeutic strategies.

Abstract

Cellular senescence has been increasingly associated with neurodegenerative disorders, potentially linking ageing-related cellular impairment with mitochondrial dysfunction, chronic inflammation, and disrupted intercellular signalling. The present study aims to explore the increasing relevance of cellular senescence among key cell types, including neurons, astrocytes, neural progenitor cells, microglia and oligodendrocyte-lineage cells across neurodegenerative ailments such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. This review discusses the findings of pre-clinical and clinical studies which suggest that senescence-associated features may contribute to neurodegeneration. Further, it provides an overview of the biomarkers used in the identification of senescence in the CNS. Also, the review examines senotherapeutic treatment approaches, highlighting their actions on different CNS cell types and the growing clinical evidence. It also points out the challenges in translating these approaches to clinical application, such as targeting specific cell types and the lack of suitable biomarkers. Collectively, present findings suggest that senescence-associated alterations may contribute to neurodegeneration, although their effects appear to vary across cell types and diseases.