Accelerated Cellular Senescence in Progressive Multiple Sclerosis: A Histopathological Study

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• The neurodegenerative mechanisms underlying progressive multiple sclerosis (P-MS) disability remain incompletely understood.
• Emerging evidence implicates cellular senescence (CS) in neurodegenerative conditions.
• This study investigates the presence and pattern of CS in P-MS.

Purpose of the Study:

• To investigate for evidence of cellular senescence (CS) in progressive multiple sclerosis (P-MS).
• To determine the distribution and cellular origins of CS in P-MS lesions.
• To correlate CS markers with disease progression and clinical outcomes.

Main Methods:

• Utilized autopsy material from P-MS patients and healthy controls.
• Assessed cellular senescence (CS) using markers 53BP1, p16, and lipofuscin in white matter lesions (WMLs), normal-appearing white matter (NAWM), and gray matter (NAGM).
• Quantified senescence-associated secretory phenotype (SASP) factors in cerebrospinal fluid (CSF) and correlated with senescent cell markers.

Main Results:

• Significantly increased p16+ and lipofuscin+ cells were found in P-MS white matter lesions (WMLs) and gray matter lesions (GMLs) compared to controls.
• Cellular senescence (CS) was identified in neurons, astrocytes, oligodendrocytes, microglia, and macrophages within lesions.
• Higher senescent cell counts in P-MS correlated with faster progression to wheelchair use and increased mortality.

Conclusions:

• Cellular senescence (CS) is a prominent feature in actively demyelinating lesions in progressive multiple sclerosis (P-MS).
• The burden of senescent cells in P-MS is linked to accelerated disease progression and poorer clinical outcomes.
• These findings highlight CS as a potential therapeutic target for P-MS.