Telomeres are vital for chromosome end protection against activation of DNA damage response. Telomere attrition leads to cell cycle arrest, which underlies cellular senescence and can restrict tissue replenishment. Although stem cells express telomerase reverse tran- scriptase, which elongates telomeric DNA, its activity is not enough to fully compensate for chronic telomere shortening. Growing lines of evidence, including telomerase knockout mouse models and human genetic diseases, suggest that a decline in the cellular renewal capacity of stem cells is a consequence of such telomere shortening. These findings highlight the critical importance of telomere protection control for human aging process, and may lead to new strategies for healthy life extension.