Abstract
Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed. Numerous recent studies have demonstrated that senescent cells, which are characterized by sustained cell cycle arrest and production of a distinct senescence-associated secretory phenotype, accumulate with age and at sites of age-related diseases throughout the body, where they actively promote tissue deterioration. Cells with features of senescence have been detected in the context of brain aging and neurodegenerative disease, suggesting that they may also promote dysfunction. Here, we discuss the evidence implicating senescent cells in neurodegenerative diseases, the mechanistic contribution of these cells that may actively drive neurodegeneration, and how these cells or their effects may be targeted therapeutically.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1208-1216 |
| Number of pages | 9 |
| Journal | Journal of Clinical Investigation |
| Volume | 128 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2 2018 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
Cellular senescence in brain aging and neurodegenerative diseases : Evidence and perspectives. / Baker, Darren J; Petersen, Ronald Carl.
In: Journal of Clinical Investigation, Vol. 128, No. 4, 02.04.2018, p. 1208-1216.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Cellular senescence in brain aging and neurodegenerative diseases
T2 - Evidence and perspectives
AU - Baker, Darren J
AU - Petersen, Ronald Carl
PY - 2018/4/2
Y1 - 2018/4/2
N2 - Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed. Numerous recent studies have demonstrated that senescent cells, which are characterized by sustained cell cycle arrest and production of a distinct senescence-associated secretory phenotype, accumulate with age and at sites of age-related diseases throughout the body, where they actively promote tissue deterioration. Cells with features of senescence have been detected in the context of brain aging and neurodegenerative disease, suggesting that they may also promote dysfunction. Here, we discuss the evidence implicating senescent cells in neurodegenerative diseases, the mechanistic contribution of these cells that may actively drive neurodegeneration, and how these cells or their effects may be targeted therapeutically.
AB - Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed. Numerous recent studies have demonstrated that senescent cells, which are characterized by sustained cell cycle arrest and production of a distinct senescence-associated secretory phenotype, accumulate with age and at sites of age-related diseases throughout the body, where they actively promote tissue deterioration. Cells with features of senescence have been detected in the context of brain aging and neurodegenerative disease, suggesting that they may also promote dysfunction. Here, we discuss the evidence implicating senescent cells in neurodegenerative diseases, the mechanistic contribution of these cells that may actively drive neurodegeneration, and how these cells or their effects may be targeted therapeutically.
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UR - http://www.scopus.com/inward/citedby.url?scp=85045038961&partnerID=8YFLogxK
U2 - 10.1172/JCI95145
DO - 10.1172/JCI95145
M3 - Review article
VL - 128
SP - 1208
EP - 1216
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -