![]() Downregulated transcripts in our model showed a significant overlap with genes regulating cognitive function ( P ≤ 1 × 10 −5), and risk for schizophrenia ( P ≤ 1 × 10 −10) and bipolar disorder ( P ≤ 0.005). ![]() RNA-sequencing and gene-set enrichment analyses revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Serially passaged progenitors demonstrated shorter telomeres ( P ≤ 0.05), and reduced rates of cell proliferation ( P ≤ 0.001), with no changes in the ability of cells to differentiate into neurons or glia. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. ![]() ![]() Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. ![]()
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December 2022
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