In mammals, profound changes in the population and functions of adult stem cells occur with age and these changes are thought to underlie functional decline and pathophysiology at the tissue and organismal levels associated with aging. SIRT1, a member of the conserved sirtuin family, functions as an anti-aging regulator for adult stem cells. Mediated through its regulatory roles in AMPK and mTORC1 pathways as well as gene expression, SIRT1 modulate the activities of genes maintaining stem cell functions and delays cellular senescence. Further investigation of the cross-talk between SIRT1 and other longevity target genes under different physiological conditions of stem cells may help us better design intervention strategies to antagonize stem cells aging.