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Abstract
Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence markers and genetically modified animal models have boosted our knowledge on the role of cellular senescence in ageing and age-related disease. The aim now is to fully elucidate its role in neurodegeneration in order to efficiently and safely exploit cellular senescence as a therapeutic target. Here, we review evidence of cellular senescence in neurons and glial cells and we discuss its putative role in Alzheimer’s disease, Parkinson’s disease and multiple sclerosis and we provide, for the first time, evidence of senescence in neurons and glia in multiple sclerosis, using the novel GL13 lipofuscin stain as a marker of cellular senescence.
Highlights
Ageing is a major risk factor for developing many neurodegenerative diseases
This dystrophic microglial phenotype is associated with functional changes, it is more abundant in neurodegenerative conditions such as Alzheimer’s disease (AD) and may even precede the onset of neurodegeneration, indicating that there may be a causal relationship between microglial senescence and neurodegeneration [100,156,157]
Senescent cells accumulate with ageing and progeroid models have provided in vivo experimental data of accelerated ageing-related degenerative pathologies
Summary
Ageing is a universal process characterized by the accumulation of biological changes that lead to the organism’s functional decline over time. Human ageing is accompanied by a gradual build-up of cognitive and physical impairment and an increased risk of developing numerous diseases including cancer, diabetes, cardiovascular, musculoskeletal and neurodegenerative conditions. Ageing is the most important risk factor for the development of neurodegenerative disease and typically, most neurodegenerative disorders manifest in the elderly [1]. Despite the differences in pathology among the two conditions, they are both typical neurodegenerative diseases characterized by chronic progressive loss of neurons and their synaptic connections manifesting with gradual functional decline [4]. Age is a recognized risk factor even for inflammatory demyelinating conditions such as multiple sclerosis (MS), which has a strong neurodegenerative component [10]. Cellular senescence is a process triggered by irreparable DNA damage that underlies normal ageing. We review the data that support a role for cellular senescence in neurodegeneration, with special focus on AD, PD and MS
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