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Astrocytes in the aging brain express characteristics of senescence‐associated secretory phenotype
Author(s) -
Salminen Antero,
Ojala Johanna,
Kaarniranta Kai,
Haapasalo Annakaisa,
Hiltunen Mikko,
Soininen Hilkka
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2011.07738.x
Subject(s) - senescence , aging brain , phenotype , biology , microbiology and biotechnology , proinflammatory cytokine , neuroinflammation , glial fibrillary acidic protein , neuroscience , astrocyte , brain aging , oxidative stress , inflammation , immunology , genetics , central nervous system , endocrinology , gene , cognition , immunohistochemistry
Cellular stress increases progressively with aging in mammalian tissues. Chronic stress triggers several signaling cascades that can induce a condition called cellular senescence. Recent studies have demonstrated that senescent cells express a senescence‐associated secretory phenotype (SASP). Emerging evidence indicates that the number of cells expressing biomarkers of cellular senescence increases in tissues with aging, which implies that cellular senescence is an important player in organismal aging. In the brain, the aging process is associated with degenerative changes, e.g. synaptic loss and white matter atrophy, which lead to progressive cognitive impairment. There is substantial evidence for the presence of oxidative, proteotoxic and metabolic stresses in aging brain. A low‐level, chronic inflammatory process is also present in brain during aging. Astrocytes demonstrate age‐related changes that resemble those of the SASP: (i) increased level of intermediate glial fibrillary acidic protein and vimentin filaments, (ii) increased expression of several cytokines and (iii) increased accumulation of proteotoxic aggregates. In addition, in vitro stress evokes a typical senescent phenotype in cultured astrocytes and, moreover, isolated astrocytes from aged brain display the proinflammatory phenotype. All of these observations indicate that astrocytes are capable of triggering the SASP and the astrocytes in aging brain display typical characteristics of cellular senescence. Bearing in mind the many functions of astrocytes, it is evident that the age‐related senescence of astrocytes enhances the decline in functional capacity of the brain. We will review the astroglial changes occurring during aging and emphasize that senescent astrocytes can have an important role in age‐related neuroinflammation and neuronal degeneration.