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Human astrocytes exhibit an increased expression of the cellular senescence biomarker p16INK4a in aged human brain and Alzheimer's Disease
Author(s) -
Bhat Rekha,
Moh Michelle,
Bitto Allessandro,
Sell Christian,
Katsetos Christos,
Garcia Fernando U,
Trojanowski John Q,
Torres Claudio
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.615.3
Subject(s) - biomarker , senescence , cellular senescence , human brain , disease , neuroscience , alzheimer's disease , biology , brain aging , astrocyte , medicine , microbiology and biotechnology , pathology , genetics , central nervous system , gene , phenotype
Astrocytes are neuroglia that provide grey matter architecture, metabolic support and control extracellular concentrations of ions and neurotransmitters. It is not known if astrocytes activate a senescence program and undergo terminal arrest in aging and age‐related diseases. Objective To demonstrate that senescent astrocytes accumulate during human brain aging and in Alzheimer‘s Disease (AD), and exhibit increased p16 accumulation. Methods Archived FFPE de‐identified human frontal cortex slides were obtained from autopsy specimens. Samples were obtained from normal subjects (36 weeks to 88 yrs, N=21), and AD subjects (53 to 90 yrs, N=11). Immunoflourescence staining for GFAP/p16 was performed in triplicates using standardized methods. Results/Conclusions There is a significant age‐dependent increase in p16‐positive astrocytes (6‐fold in aged brains vs. fetal brains, P<0.001, Fig. 1). AD brains show greater p16 accumulation compared to age‐matched controls, with the difference being more striking in the 60–79 years age group, compared to the > 80 years age group (Fig. 2), which raises the possibility that the chain of events leading to cellular senescence may already have occurred in the older brains. Astrocyte senescence during aging and AD may be due to effects of oxidative stress and/or β‐amyloid, which will be clarified by further studies.