TY - JOUR
T1 - Lessons from inducible pluripotent stem cell models on neuronal senescence in aging and neurodegeneration
AU - de Luzy, Isabelle R.
AU - Lee, Michael K.
AU - Mobley, William C.
AU - Studer, Lorenz
N1 - Publisher Copyright:
© Springer Nature America, Inc. 2024.
PY - 2024/3
Y1 - 2024/3
N2 - Age remains the central risk factor for many neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Although the mechanisms of aging are complex, the age-related accumulation of senescent cells in neurodegeneration is well documented and their clearance can alleviate disease-related features in preclinical models. Senescence-like characteristics are observed in both neuronal and glial lineages, but their relative contribution to aging and neurodegeneration remains unclear. Human pluripotent stem cell-derived neurons provide an experimental model system to induce neuronal senescence. However, the extensive heterogeneity in the profile of senescent neurons and the methods to assess senescence remain major challenges. Here, we review the evidence of cellular senescence in neuronal aging and disease, discuss human pluripotent stem cell-based model systems used to investigate neuronal senescence and propose a panel of cellular and molecular hallmarks to characterize senescent neurons. Understanding the role of neuronal senescence may yield novel therapeutic opportunities in neurodegenerative disease.
AB - Age remains the central risk factor for many neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis. Although the mechanisms of aging are complex, the age-related accumulation of senescent cells in neurodegeneration is well documented and their clearance can alleviate disease-related features in preclinical models. Senescence-like characteristics are observed in both neuronal and glial lineages, but their relative contribution to aging and neurodegeneration remains unclear. Human pluripotent stem cell-derived neurons provide an experimental model system to induce neuronal senescence. However, the extensive heterogeneity in the profile of senescent neurons and the methods to assess senescence remain major challenges. Here, we review the evidence of cellular senescence in neuronal aging and disease, discuss human pluripotent stem cell-based model systems used to investigate neuronal senescence and propose a panel of cellular and molecular hallmarks to characterize senescent neurons. Understanding the role of neuronal senescence may yield novel therapeutic opportunities in neurodegenerative disease.
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U2 - 10.1038/s43587-024-00586-3
DO - 10.1038/s43587-024-00586-3
M3 - Review article
C2 - 38429379
AN - SCOPUS:85186462942
SN - 2662-8465
VL - 4
SP - 309
EP - 318
JO - Nature Aging
JF - Nature Aging
IS - 3
ER -