Table 1.

DNA damage accumulation upon aging in HSCs

Increased DNA damage and DNA mutations upon aging in HSCs and the hematopoietic system contribute to aging of HSCs
YES	NO
accumulation of γH2AX foci, indicative of persistent DNA DSBs (Rossi et al. 2005)	γH2AX foci can also indicate replication and ribosome biogenesis stress in aged HSCs (Flach et al. 2014b) in aged hair follicle stem cells, γH2AX foci are associated with persistent chromatin alterations but not DNA DSBs (Schuler and Rübe 2013)
comet assay experiments in aged HSCs showed a twofold increase in DNA damage level in steady state (Beerman et al. 2014; Moehrle et al. 2015)	DNA damage level decreased upon cell cycle entry of aged HSCs (Beerman et al. 2014)
mutation frequency in human and murine BM is increased twofold upon aging (Moehrle et al. 2015; Cancer Genome Atlas Research Network 2013; Genovese et al. 2014; Welch et al. 2012)	mutation frequency in aged BM decreases upon DNA damage (Moehrle et al. 2015)
incidence of leukemia increases dramatically upon aging (Armitage and Doll 1954; Nordling 1953; Rozhok, Salstrom, and DeGregori 2016)	in aging-associated leukemia only very few driver mutations could be identified (McKerrell et al. 2015; Papaemmanuil et al. 2013; Xie et al. 2014; Jaiswal et al. 2014)
mouse models with altered DNA damage response genes show BM failure and depletion of the HSCs pool (Barlow et al. 1996; Bender et al. 2002; Dumble et al. 2007; Ito et al. 2004; Ito et al. 2006; Kenyon and Gerson 2007; Nijnik et al. 2007; Rossi et al. 2007; Tothova et al. 2007)	in normal aging there is an increase in the number of HSCs (de Haan, Nijhof, and Van Zant 1997; Rossi et al. 2005)