Table 1.

Characteristics of aging NPCs compared with an expanded list of the hallmarks of cancer

Expanded list of the hallmarks of cancer	Actual characteristics of aged NPCs and their niche	Potential mechanisms underlying age-related changes
Increased cell cycle progression	Large quiescent population; increased cell cycle re-entry in the remaining cycling population (Stoll et al., 2011a)	Decreased p53 expression (Mikheev et al., 2009); increased p16 expression (Molofsky et al., 2006)
Self-sufficiency in growth factor signaling	Retained sensitivity to growth factors FGF and EGF; fewer growth factors in aged neurogenic niche (Jin et al., 2003)	Aged astrocytes produce fewer growth factors (Jin et al., 2003)
Insensitivity to antigrowth signals	Retained responses to anti-growth signal TGFβ; more anti-growth factors in aged neurogenic niche (Buckwalter et al., 2006)	Aged astrocytes produce more TGFb (Buckwalter et al., 2006)
Genetic instability	Increased chromosomal loss of heterozygosity (Bailey et al., 2004)	Accumulation of mutations over time; loss of telomeres (Ferron et al., 2009)
Escape from apoptosis	Increased apoptosis (Ahlenius et al., 2009)	Not known
Angiogenesis and neovascularization	Decreased vascularity and cerebral blood flow (Aanerud et al., 2012)	Loss of pro-angiogenic VEGF and other factors (Shetty et al., 2005)
Invasion into surrounding tissue	No change in migratory potential of actively cycling cells (Stoll et al., 2011a)
Escape from immune destruction	Increased microglia and cytokine production (Kuzumaki et al., 2010)	Not known
Decreased aerobic respiration and increased glycolysis	Decreased aerobic respiration but no compensatory glycolytic switch (Stoll et al., 2011b)	Lower mitochondrial content (Stoll et al., 2011b)

NPC, neural progenitor cells; VEGF, vascular endothelial growth factor. Listed is an updated list of the hallmarks of cancer, originally escribed by Hanahan and Weinberg, with the addition of several features that have recently been recognized as key events during oncogenesis. The observed cellular activities of aging NPCs are listed; these characteristics largely describe a senescent phenotype both within the aging cell and throughout the aging brain. Compensatory mechanisms must balance the forces of senescence and oncogenesis in NPCs. For example, multiple pathways may be particularly important in the case of metabolism, Aged NPCs consume less oxygen, but do not secrete more lactate than young adult NPCs, suggesting that these cells have deficits in aerobic metabolism but have not acquired a greater dependence upon glycolytic metabolism.