Nature Communications, Published online: 06 June 2026; doi:10.1038/s41467-026-74021-z The study shows that disruption of calcium homeostasis triggers the aberrant accumulation of S100A6 in the cytoplasm, thereby promoting Hutchinson-Gilford Progeria Syndrome (HGPS) and natural aging. Mianserin was found to effectively retard the aging process and significantly extend the lifespan of both progeroid and naturally aged mice by restoring calcium homeostasis.