When sperm age, their RNA code hits a cliff

Advanced paternal age is associated with reduced fertility and increased health risks in offspring, but the molecular events that convert “chronological age” into “biological risk” remain incompletely defined. Recent work by Shi et al (2026) uncovers a conserved sharp transition, i.e., an “aging cliff”, in mouse and human sperm small non-coding RNA profiles, suggesting roles of age-dependent remodeling of the sperm epigenetic playload in early embryogenesis and transgenerational outcomes. Recent modification-aware RNA sequencing reveals unexpected shifts in sperm small non-coding RNA profiles during lifespan with functional relevance for gene expression.