GeroScience · Nov 7, 2026
Near-null gene-level association between the hypothalamic neural stem cell microRNA targetome and hypothalamic aging transcriptomes
By Sanker V, Constantinou S, Desai A et al.
Adult hypothalamic neural stem and progenitor cells (htNSCs) influence aging partly through exosome-associated microRNA (miRNA) cargo, yet how their miRNA targetome relates to hypothalamic aging remains unclear. We mapped htNSC-biased miRNAs onto miRTarBase to define a 1777-gene target union and tested whether gene-level target burden aligns with public hypothalamic aging transcriptomes. The primary Spearman correlation between miRTarBase-weighted burden and GSE188646 aging log fold-change is near zero (ρ = 0.0069, P = 0.784; n = 1579 genes). Equivalence was tested at |ρ| = 0.10. That margin was fixed before the test was computed, but only after the near-zero correlation had been observed, and it was not specified before the study began. The bootstrap 95% CI is [ − 0.042, 0.056] (TOST P = 1.0 × 10⁻⁴; Fig. R1). Because the interval treats genes as independent, it likely overstates precision. Statistical equivalence inside this bound is not biological equivalence, and it does not exclude cell-type-specific regulation. The near-zero correlation is stable across a miRNA-selection grid (Fig. R2). Descriptive Hallmark over-representation recovers broad stress and inflammatory terms. In five covariate-matched nulls, Apoptosis has an unadjusted empirical P of 0.009 (Bonferroni-adjusted P = 0.045; Fig. R3). Those five terms were taken from a larger Hallmark screen, and Apoptosis does not survive a screen-wide correction, so it is not reported as pathway specificity. Unadjusted |logFC| attenuation and third-ventricle niche localization remain exploratory. Piezo1/LIFU is a future hypothesis only. These analyses describe a near-zero gene-level rank association in the datasets studied. They do not show biological independence or independent hypothalamic replication.