Arguing for Hypothalamic Neural Stem Cell Signaling to Support Function in Other Tissues
Researchers propose that neural stem cells in the hypothalamus play a crucial role in maintaining a youthful environment in various tissues by secreting factors carried into circulation in exosomes. This signaling process, when disrupted with age, contributes to the aging process and age-related dysfunction. While it’s difficult to determine the exact significance of this mechanism among others, it is clear that different components in the body rely on each other for proper function. Age-related changes in organisms can potentially be reversed by factors in young blood. The secretion of exosomal microRNAs by hypothalamic neural stem cells may regulate the aging rate by improving physiological fitness in young animals. Further research is needed to determine the specific molecular mechanisms behind this process.
Using miRNA-target gene interactions and single-cell transcriptomic data, researchers have identified pathways controlled by these miRNAs and how age-related decline of hypothalamic neural stem cells affects specific miRNA levels in the cerebrospinal fluid (CSF). These miRNAs appear to modulate pathways associated with senescence and cellular stress response by targeting genes such as Cdkn2a, Rps27, and Txnip. The impact of age-related loss of exosomal miRNAs is most prominent in the oligodendrocyte lineage, leading to derepression of target genes. Heterochronic parabiosis has shown to reverse age-related upregulation of specific miRNA-targeted genes, particularly in brain endothelial cells, suggesting an anti-senescence mechanism triggered by the secretion of hypothalamic stem cell-derived exosomal miRNAs.
