The stem cell niche is a specialized microenvironment for stem cells in an adult tissue. The niche provides cues for the maintenance and regulation of stem cell activities and thus presents a target for potential rejuvenating strategies. García‐Prat et al . found that in the heterogeneous population of quiescent stem cells of skeletal muscles, a fraction of cells responsible for regeneration and having genuine ‘stemness’ properties deteriorates only in extremely old age. An essential tool used in this analysis of stem cell–niche interactions is the computational tool, NicheHotSpotter, which proved to be instrumental for identifying niche and cell signalling factors that contribute to the maintenance of the pool of genuine quiescent stem cells. NicheHotSpotter predicts candidate factors by analysing signalling interactome and gene regulatory network data in combination with expression profiles. The effect of the niche environment on stem cells is modelled as a mean field of niche cues that induce sustained activation or inhibition of signalling pathways. In this way, NicheHotSpotter has been successful in delineating novel strategies to enhance stemness, which may rejuvenate skeletal muscle cells at the extreme old age.