Hair follicle stem cells (HFSCs) are maintained in a quiescent state until 
activated to grow, but the mechanisms that reactivate the quiescent HFSC 
reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair 
follicle life-cycle transition from telogen to anagen phase, resulting in delay 
of hair growth. Conversely, Sirt7 overexpression during telogen phase 
facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, 
Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and 
HFSC-specific Sirt7 knockout mice (Sirt7f/f ;K15-Cre) exhibit a similar hair 
growth delay. At the molecular level, Sirt7 interacts with and deacetylates the 
transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal 
degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen 
entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear 
retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair 
growth in Sirt7-/- mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and 
exogenous Sirt7 overexpression promotes hair growth in aged animals. These data 
reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair 
follicle cycle initiation.