Astrocyte senescence may drive alterations in GFAPα, CDKN2A p14^ARF, and TAU3 transcript expression and contribute to cognitive decline.

ABSTRACT: The accumulation of senescent cells in tissues is causally linked to the development of several age-related diseases; the removal of senescent glial cells in animal models prevents Tau accumulation and cognitive decline. Senescent cells can arise through several distinct mechanisms; one such mechanism is dysregulation of alternative splicing. In this study, we characterised the senescent cell phenotype in primary human astrocytes in terms of SA-β-Gal staining and SASP secretion, and then assessed splicing factor expression and candidate gene splicing patterns. Finally, we assessed associations between expression of dysregulated isoforms and premature cognitive decline in 197 samples from the InCHIANTI study of ageing, where expression was present in both blood and brain. We demonstrate her

SUBMITTER: Lye JJ 

PROVIDER: S-EPMC6885035 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature