Age-related cognitive decline: Can neural stem cells help us?

Aging

Volumn 4, Issue 3, 2012, Pages 176-186

  Artegiani, Benedetta ^a   Calegari, Federico ^a  

^a MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

Author keywords

Adult neurogenesis; Aging; Neural stem cells; Regenerative therapies

Indexed keywords

EID: 84863328156     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.100446     Document Type: Article

References (152)

1. Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000; 100:157-168.
2. Rossi DJ, Jamieson CH and Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008; 132:681-696.
3. Rando TA. Stem cells, ageing and the quest for immortality. Nature. 2006; 441:1080-1086.
4. Fuchs E. The tortoise and the hair: slow-cycling cells in the stem cell race. Cell. 2009; 137:811-819.
5. Morrison SJ and Kimble J. Asymmetric and symmetric stemcell divisions in development and cancer. Nature. 2006; 441:1068-1074.
6. Liu L and Rando TA. Manifestations and mechanisms of stem cell aging. J Cell Biol. 2011; 193:257-266.
7. Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009; 361:1475-1485.
8. Haigis MC and Yankner BA. The aging stress response. Mol Cell. 2010; 40:333-344.
9. Kirkwood TB. Understanding the odd science of aging. Cell. 2005; 120:437-447.
10. Balaban RS, Nemoto S and Finkel T. Mitochondria, oxidants, and aging. Cell. 2005; 120:483-495.
11. Sharpless NE and DePinho RA. How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol. 2007; 8:703-713.
12. Sahin E and Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010; 464:520-528.
13. Ruzankina Y, Pinzon-Guzman C, Asare A, Ong T, Pontano L, Cotsarelis G, Zediak VP, Velez M, Bhandoola A and Brown EJ. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell. 2007; 1:113-126.
14. Yassa MA and Stark CE. Pattern separation in the hippocampus. Trends Neurosci. 2011; 34:515-525.
15. Deng W, Aimone JB and Gage FH. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci. 2010; 11:339-350.
16. Kempermann G. The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci. 2008; 31:163-169.
17. Ming GL and Song H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 2011; 70:687-702.
18. Marin-Burgin A and Schinder AF. Requirement of adult-born neurons for hippocampus-dependent learning. Behav Brain Res. 2012; 227:391-399.
19. Altman J and Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol. 1965; 124:319-335.
20. Kuhn HG, Dickinson-Anson H and Gage FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci. 1996; 16:2027-2033.
21. Seki T and Arai Y. Age-related production of new granule cells in the adult dentate gyrus. Neuroreport. 1995; 6:2479-2482.
22. Gage FH, Kelly PA and Bjorklund A. Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats. J Neurosci. 1984; 4:2856-2865.
23. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW and van Praag H. When neurogenesis encounters aging and disease. Trends Neurosci. 2010; 33:569-579.
24. Bishop NA, Lu T and Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature. 2010; 464:529-535.
25. Gazzaley A, Cooney JW, Rissman J and D'Esposito M. Topdown suppression deficit underlies working memory impairment in normal aging. Nat Neurosci. 2005; 8:1298-1300.
26. Prakash RS, Erickson KI, Colcombe SJ, Kim JS, Voss MW and Kramer AF. Age-related differences in the involvement of the prefrontal cortex in attentional control. Brain Cogn. 2009; 71:328-335.
27. Wang M, Gamo NJ, Yang Y, Jin LE, Wang XJ, Laubach M, Mazer JA, Lee D and Arnsten AF. Neuronal basis of age-related working memory decline. Nature. 2011; 476:210-213.
28. Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza PV and Abrous DN. Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis. Proc Natl Acad Sci U S A. 2003; 100:14385-14390.
29. Montaron MF, Drapeau E, Dupret D, Kitchener P, Aurousseau C, Le Moal M, Piazza PV and Abrous DN. Lifelong corticosterone level determines age-related decline in neurogenesis and memory. Neurobiol Aging. 2006; 27:645-654.
30. Driscoll I, Howard SR, Stone JC, Monfils MH, Tomanek B, Brooks WM and Sutherland RJ. The aging hippocampus: a multilevel analysis in the rat. Neuroscience. 2006; 139:1173-1185.
31. Wimmer ME, Hernandez PJ, Blackwell J and Abel T. Aging impairs hippocampus-dependent long-term memory for object location in mice. Neurobiol Aging. 2011; http://dx.doi.org/10.1016/j.neurobiolaging.2011.07.007.
32. Aizawa K, Ageyama N, Yokoyama C and Hisatsune T. Agedependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys. Exp Anim. 2009; 58:403-407.
33. Bizon JL and Gallagher M. Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline. Eur J Neurosci. 2003; 18:215-219.
34. Merrill DA, Karim R, Darraq M, Chiba AA and Tuszynski MH. Hippocampal cell genesis does not correlate with spatial learning ability in aged rats. J Comp Neurol. 2003; 459:201-207.
35. Bizon JL, Lee HJ and Gallagher M. Neurogenesis in a rat model of age-related cognitive decline. Aging Cell. 2004; 3:227-234.
36. Kempermann G, Kuhn HG and Gage FH. Experience-induced neurogenesis in the senescent dentate gyrus. J Neurosci. 1998; 18:3206-3212.
37. Kempermann G, Gast D and Gage FH. Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long-term environmental enrichment. Ann Neurol. 2002; 52:135-143.
38. van Praag H, Shubert T, Zhao C and Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005; 25:8680-8685.
39. Leuner B, Kozorovitskiy Y, Gross CG and Gould E. Diminished adult neurogenesis in the marmoset brain precedes old age. Proc Natl Acad Sci U S A. 2007; 104:17169-17173.
40. Walter J, Keiner S, Witte OW and Redecker C. Age-related effects on hippocampal precursor cell subpopulations and neurogenesis. Neurobiol Aging. 2011; 32:1906-1914.
41. Jinno S. Decline in adult neurogenesis during aging follows a topographic pattern in the mouse hippocampus. J Comp Neurol. 2011; 519:451-466.
42. Alonso G. Proliferation of progenitor cells in the adult rat brain correlates with the presence of vimentin-expressing astrocytes. Glia. 2001; 34:253-266.
43. Hattiangady B and Shetty AK. Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging. 2008; 29:129-147.
44. Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Gotz M, Haas CA, Kempermann G, Taylor V and Giachino C. Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell. 2010; 6:445-456.
45. Aizawa K, Ageyama N, Terao K and Hisatsune T. Primatespecific alterations in neural stem/progenitor cells in the aged hippocampus. Neurobiol Aging. 2011; 32:140-150.
46. Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA, Fishell G, Koulakov A and Enikolopov G. Divisioncoupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell. 2011; 8:566-579.
47. Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL and Song H. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell. 2011; 145:1142-1155.
48. Blagosklonny MV. Cell cycle arrest is not senescence. Aging. 2011; 3:94-101.
49. Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D and Kempermann G. Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging. 2006; 27:1505-1513.
50. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011; 108:3017-3022.
51. Kim YP, Kim H, Shin MS, Chang HK, Jang MH, Shin MC, Lee SJ, Lee HH, Yoon JH, Jeong IG and Kim CJ. Age-dependence of the effect of treadmill exercise on cell proliferation in the dentate gyrus of rats. Neurosci Lett. 2004; 355:152-154.
52. Rao MS, Hattiangady B and Shetty AK. Status epilepticus during old age is not associated with enhanced hippocampal neurogenesis. Hippocampus. 2008; 18:931-944.
53. Darsalia V, Heldmann U, Lindvall O and Kokaia Z. Strokeinduced neurogenesis in aged brain. Stroke. 2005; 36:1790-1795.
54. Yagita Y, Kitagawa K, Ohtsuki T, Takasawa K, Miyata T, Okano H, Hori M and Matsumoto M. Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke. 2001; 32:1890-1896.
55. Walter J, Keiner S, Witte OW and Redecker C. Differential stroke-induced proliferative response of distinct precursor cell subpopulations in the young and aged dentate gyrus. Neuroscience. 2010; 169:1279-1286.
56. Rao MS, Hattiangady B, Abdel-Rahman A, Stanley DP and Shetty AK. Newly born cells in the ageing dentate gyrus display normal migration, survival and neuronal fate choice but endure retarded early maturation. Eur J Neurosci. 2005; 21:464-476.
57. Rao MS, Hattiangady B and Shetty AK. The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus. Aging cell. 2006; 5:545-558.
58. McDonald HY and Wojtowicz JM. Dynamics of neurogenesis in the dentate gyrus of adult rats. Neurosci Lett. 2005; 385:70-75.
59. Palmer TD, Willhoite AR and Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol. 2000; 425:479-494.
60. Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM and Doetsch F. A specialized vascular niche for adult neural stem cells. Cell Stem Cell. 2008; 3:279-288.
61. Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM and Alvarez-Buylla A. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell. 2008; 3:265-278.
62. Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, Roysam B and Temple S. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell. 2008; 3:289-300.
63. Riddle DR, Sonntag WE and Lichtenwalner RJ. Microvascular plasticity in aging. Ageing Res Rev. 2003; 2:149-168.
64. Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S and et al. Cerebral blood flow, blood volume and oxygen utilization. Normal values and effect of age. Brain. 1990; 113:27-47.
65. Ajmani RS, Metter EJ, Jaykumar R, Ingram DK, Spangler EL, Abugo OO and Rifkind JM. Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function. Neurobiol Aging. 2000; 21:257-269.
66. Bentourkia M, Bol A, Ivanoiu A, Labar D, Sibomana M, Coppens A, Michel C, Cosnard G and De Volder AG. Comparison of regional cerebral blood flow and glucose metabolism in the normal brain: effect of aging. J Neurol Sci. 2000; 181:19-28.
67. Heo S, Prakash RS, Voss MW, Erickson KI, Ouyang C, Sutton BP and Kramer AF. Resting hippocampal blood flow, spatial memory and aging. Brain Res. 2010; 1315:119-127.
68. Studer L, Csete M, Lee SH, Kabbani N, Walikonis J, Wold B and McKay R. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci. 2000; 20:7377-7383.
69. Morrison SJ, Csete M, Groves AK, Melega W, Wold B and Anderson DJ. Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. J Neurosci. 2000; 20:7370-7376.
70. Storch A, Lester HA, Boehm BO and Schwarz J. Functional characterization of dopaminergic neurons derived from rodent mesencephalic progenitor cells. J Chem Neuroanat. 2003; 26:133-142.
71. Storch A, Paul G, Csete M, Boehm BO, Carvey PM, Kupsch A and Schwarz J. Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol. 2001; 170:317-325.
72. Pistollato F, Chen HL, Rood BR, Zhang HZ, D'Avella D, Denaro L, Gardiman M, te Kronnie G, Schwartz PH, Favaro E, Indraccolo S, Basso G and Panchision DM. Hypoxia and HIF1alpha repress the differentiative effects of BMPs in high-grade glioma. Stem Cells. 2009; 27:7-17.
73. Zheng X, Linke S, Dias JM, Zheng X, Gradin K, Wallis TP, Hamilton BR, Gustafsson M, Ruas JL, Wilkins S, Bilton RL, Brismar K, Whitelaw ML, et al. Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways. Proc Natl Acad Sci U S A. 2008; 105:3368-3373.
74. Zhang K, Zhu L and Fan M. Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases. Front Mol Neurosci. 2011; 4:5.
75. Mazumdar J, O'Brien WT, Johnson RS, LaManna JC, Chavez JC, Klein PS and Simon MC. O2 regulates stem cells through Wnt/beta-catenin signalling. Nat Cell Biol. 2010; 12:1007-1013.
76. Rabie T, Kunze R and Marti HH. Impaired hypoxic response in senescent mouse brain. Int J Dev Neurosci. 2011; 29:655-661.
77. Benderro GF and Lamanna JC. Hypoxia-induced angiogenesis is delayed in aging mouse brain. Brain Res. 2011; 1389:50-60.
78. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A, Lucin KM, Czirr E, Park JS, et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011; 477:90-94.
79. Herbert J, Goodyer IM, Grossman AB, Hastings MH, de Kloet ER, Lightman SL, Lupien SJ, Roozendaal B and Seckl JR. Do corticosteroids damage the brain? J Neuroendocrinol. 2006; 18:393-411.
80. Reul JM and de Kloet ER. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology. 1985; 117:2505-2511.
81. Han F, Ozawa H, Matsuda K, Nishi M and Kawata M. Colocalization of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus and hypothalamus. Neurosci Res. 2005; 51:371-381.
82. Garcia A, Steiner B, Kronenberg G, Bick-Sander A and Kempermann G. Age-dependent expression of glucocorticoidand mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Aging Cell. 2004; 3:363-371.
83. Gould E, Cameron HA, Daniels DC, Woolley CS and McEwen BS. Adrenal hormones suppress cell division in the adult rat dentate gyrus. J Neurosci. 1992; 12:3642-3650.
84. Cameron HA and Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience. 1994; 61:203-209.
85. Cameron HA and McKay RD. Restoring production of hippocampal neurons in old age. Nat Neurosci. 1999; 2:894-897.
86. Montaron MF, Petry KG, Rodriguez JJ, Marinelli M, Aurousseau C, Rougon G, Le Moal M and Abrous DN. Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus. Eur J Neurosci. 1999; 11:1479-1485.
87. Garrido P, de Blas M, Del Arco A, Segovia G and Mora F. Aging increases basal but not stress-induced levels of corticosterone in the brain of the awake rat. Neurobiol Aging. 2012; 33:375-382.
88. Lai M, Hibberd CJ, Gluckman PD and Seckl JR. Reduced expression of insulin-like growth factor 1 messenger RNA in the hippocampus of aged rats. Neurosci Lett. 2000; 288:66-70.
89. Shetty AK, Hattiangady B and Shetty GA. Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes. Glia. 2005; 51:173-186.
90. Bernal GM and Peterson DA. Phenotypic and gene expression modification with normal brain aging in GFAPpositive astrocytes and neural stem cells. Aging Cell. 2011; 10:466-482.
91. Chadashvili T and Peterson DA. Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain. J Comp Neurol. 2006; 498:1-15.
92. Sun LY, Al-Regaiey K, Masternak MM, Wang J and Bartke A. Local expression of GH and IGF-1 in the hippocampus of GHdeficient long-lived mice. Neurobiol Aging. 2005; 26:929-937.
93. Trejo JL, Llorens-Martin MV and Torres-Aleman I. The effects of exercise on spatial learning and anxiety-like behavior are mediated by an IGF-I-dependent mechanism related to hippocampal neurogenesis. Mol Cell Neurosci. 2008; 37:402-411.
94. Aberg MA, Aberg ND, Hedbacker H, Oscarsson J and Eriksson PS. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci. 2000; 20:2896-2903.
95. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE and Riddle DR. Intracerebroventricular infusion of insulinlike growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience. 2001; 107:603-613.
96. Zhao M, Li D, Shimazu K, Zhou YX, Lu B and Deng CX. Fibroblast growth factor receptor-1 is required for long-term potentiation, memory consolidation, and neurogenesis. Biol Psychiatry. 2007; 62:381-390.
97. Kuhn HG, Winkler J, Kempermann G, Thal LJ and Gage FH. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci. 1997; 17:5820-5829.
98. Wagner JP, Black IB and DiCicco-Bloom E. Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J Neurosci. 1999; 19:6006-6016.
99. Jin K, Sun Y, Xie L, Batteur S, Mao XO, Smelick C, Logvinova A and Greenberg DA. Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell. 2003; 2:175-183.
100. Rai KS, Hattiangady B and Shetty AK. Enhanced production and dendritic growth of new dentate granule cells in the middleaged hippocampus following intracerebroventricular FGF-2 infusions. European J Neurosci. 2007; 26:1765-1779.
101. Schanzer A, Wachs FP, Wilhelm D, Acker T, Cooper-Kuhn C, Beck H, Winkler J, Aigner L, Plate KH and Kuhn HG. Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. Brain Pathol. 2004; 14:237-248.
102. Sun Y, Jin K, Childs JT, Xie L, Mao XO and Greenberg DA. Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: evidence from knockout mice and growth factor administration. Dev Biol. 2006; 289:329-335.
103. Jin K, Zhu Y, Sun Y, Mao XO, Xie L and Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A. 2002; 99:11946-11950.
104. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D and During MJ. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet. 2004; 36(8):827-835.
105. Sonntag WE, Ramsey M and Carter CS. Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging. Ageing Res Rev. 2005; 4:195-212.
106. Mudo G, Bonomo A, Di Liberto V, Frinchi M, Fuxe K and Belluardo N. The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain. J Neural Transm. 2009; 116:995-1005.
107. van Praag H, Kempermann G and Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 1999; 2:266-270.
108. van Praag H. Exercise and the brain: something to chew on. Trends Neurosci. 2009; 32:283-290.
109. Trejo JL, Carro E and Torres-Aleman I. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci. 2001; 21:1628-1634.
110. Glasper ER, Llorens-Martin MV, Leuner B, Gould E and Trejo JL. Blockade of insulin-like growth factor-I has complex effects on structural plasticity in the hippocampus. Hippocampus. 2010; 20:706-712.
111. Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, Kuo CJ and Palmer TD. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci. 2003; 18:2803-2812.
112. Bishop NA and Guarente L. Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat Rev Genet. 2007; 8:835-844.
113. Blagosklonny MV. Calorie restriction: decelerating mTORdriven aging from cells to organisms (including humans). Cell Cycle. 2010; 9:683-688.
114. Blagosklonny MV. Aging, stem cells, and mammalian target of rapamycin: a prospect of pharmacologic rejuvenation of aging stem cells. Rejuvenation Res. 2008; 11:801-808.
115. Castilho RM, Squarize CH, Chodosh LA, Williams BO and Gutkind JS. mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell. 2009; 5:279-289.
116. Lee J, Seroogy KB and Mattson MP. Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice. J Neurochem. 2002; 80:539-547.
117. Bondolfi L, Ermini F, Long JM, Ingram DK and Jucker M. Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice. Neurobiol Aging. 2004; 25:333-340.
118. Levenson CW and Rich NJ. Eat less, live longer? New insights into the role of caloric restriction in the brain. Nutrition Rev. 2007; 65:412-415.
119. Kim JY, Duan X, Liu CY, Jang MH, Guo JU, Pow-anpongkul N, Kang E, Song H and Ming GL. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron. 2009; 63:761-773.
120. Prolla TA and Mattson MP. Molecular mechanisms of brain aging and neurodegenerative disorders: lessons from dietary restriction. Trends Neurosci. 2001; 24(11 Suppl):S21-31.
121. Fabel K and Kempermann G. Physical activity and the regulation of neurogenesis in the adult and aging brain. Neuromolecular Med. 2008; 10:59-66.
122. Cotman CW, Berchtold NC and Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007; 30:464-472.
123. Suh H, Deng W and Gage FH. Signaling in adult neurogenesis. Annu Rev Cell Dev Biol. 2009; 25:253-275.
124. Doetsch F. A niche for adult neural stem cells. Curr Opin Genet Dev. 2003; 13:543-550.
125. Ninkovic J and Gotz M. Signaling in adult neurogenesis: from stem cell niche to neuronal networks. Curr Opin Neurobiol. 2007; 17:338-344.
126. Ohnuma S and Harris WA. Neurogenesis and the cell cycle. Neuron. 2003; 40:199-208.
127. Dehay C and Kennedy H. Cell-cycle control and cortical development. Nat Rev Neurosci. 2007; 8:438-450.
128. Salomoni P and Calegari F. Cell cycle control of mammalian neural stem cells: putting a speed limit on G1. Trends Cell Biol. 2010; 5:332-342.
129. Beukelaers P, Vandenbosch R, Caron N, Nguyen L, Moonen G and Malgrange B. Cycling or not cycling: cell cycle regulatory molecules and adult neurogenesis. Cell Mol Life Sci. 2011: DOI 10.1007/s00018-011-0880-6.
130. Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L and Sharpless NE. Ink4a/Arf expression is a biomarker of aging. J Clin Invest. 2004; 114:1299-1307.
131. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE and Morrison SJ. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature. 2006; 443:448-452.
132. Molofsky AV, He S, Bydon M, Morrison SJ and Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005; 19:1432-1437.
133. Kohman RA, Rodriguez-Zas SL, Southey BR, Kelley KW, Dantzer R and Rhodes JS. Voluntary wheel running reverses ageinduced changes in hippocampal gene expression. PloS One. 2011; 6:e22654.
134. Olariu A, Cleaver KM and Cameron HA. Decreased neurogenesis in aged rats results from loss of granule cell precursors without lengthening of the cell cycle. J Comp Neurol. 2007; 501:659-667.
135. Stoll EA, Habibi BA, Mikheev AM, Lasiene J, Massey SC, Swanson KR, Rostomily RC and Horner PJ. Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone. Stem Cells. 2011; 29:2005-2017.
136. Lange C, Huttner WB and Calegari F. Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors. Cell Stem Cell. 2009; 5:320-331.
137. Artegiani B, Lindemann D and Calegari F. Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain. J Exp Med. 2011; 208:937-948.
138. Beukelaers P, Vandenbosch R, Caron N, Nguyen L, Belachew S, Moonen G, Kiyokawa H, Barbacid M, Santamaria D and Malgrange B. Cdk6-dependent regulation of G(1) length controls adult neurogenesis. Stem Cells. 2011; 29:713-724.
139. Kowalczyk A, Filipkowski RK, Rylski M, Wilczynski GM, Konopacki FA, Jaworski J, Ciemerych MA, Sicinski P and Kaczmarek L. The critical role of cyclin D2 in adult neurogenesis. J Cell Biol. 2004; 167:209-213.
140. Calegari F and Huttner WB. An inhibition of cyclindependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis. J Cell Sci. 2003; 116:4947-4955.
141. Lange C and Calegari F. Cdks and cyclins link G(1) length and differentiation of embryonic, neural and hematopoietic stem cells. Cell Cycle. 2010; 9:1893-1900.
142. Kempermann G, Gast D, Kronenberg G, Yamaguchi M and Gage FH. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development. 2003; 130:391-399.
143. Morgenstern NA, Lombardi G and Schinder AF. Newborn granule cells in the ageing dentate gyrus. J Physiol. 2008; 586:3751-3757.
144. Kempermann G, Kuhn HG and Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature. 1997; 386:493-495.
145. Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS, Fenton AA, Dranovsky A and Hen R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature. 2011; 472:466-470.
146. Bernal GM and Peterson DA. Neural stem cells as therapeutic agents for age-related brain repair. Aging cell. 2004; 3:345-351.
147. Lindvall O and Kokaia Z. Stem cells for the treatment of neurological disorders. Nature. 2006; 441:1094-1096.
148. Lie DC, Song H, Colamarino SA, Ming GL and Gage FH. Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol. 2004; 44:399-421.
149. Minger SL, Ekonomou A, Carta EM, Chinoy A, Perry RH and Ballard CG. Endogenous neurogenesis in the human brain following cerebral infarction. Regen Med. 2007; 2:69-74.
150. Jin K, Wang X, Xie L, Mao XO, Zhu W, Wang Y, Shen J, Mao Y, Banwait S and Greenberg DA. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A. 2006; 103:13198-13202.
151. Macas J, Nern C, Plate KH and Momma S. Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain. J Neurosci. 2006; 26:13114-13119.
152. Dunnett SB and Rosser AE. Clinical translation of cell transplantation in the brain. Curr Opin Organ Transplant. 2011; 16:632-639.