Abstract
Stem cell dysfunction is associated with age-related degenerative and proliferative diseases. Recent work in a range of model organisms has focused on characterizing the causes and consequences of stem cell aging. The insight obtained from these studies is likely to impact our ability to promote healthy aging and to develop new therapies against age-related diseases. This book provides an overview of such studies, aiming to present a comprehensive assessment of the current status of the field.
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Abou-Khalil R, Brack AS (2010) Muscle stem cells and reversible quiescence: the role of sprouty. Cell Cycle 9:2575–2580
Aguilaniu H, Gustafsson L, Rigoulet M, Nystrom T (2003) Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299:1751–1753
Amcheslavsky A, Jiang J, Ip YT (2009) Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4:49–61
Amcheslavsky A, Ito N, Jiang J, Ip YT (2011) Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells. J Cell Biol 193:695–710
Apidianakis Y, Pitsouli C, Perrimon N, Rahme L (2009) Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc Natl Acad Sci U S A 106:20883–20888
Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295:502–505
Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457:608–611
Barnes AI, Boone JM, Jacobson J, Partridge L, Chapman T (2006) No extension of lifespan by ablation of germ line in Drosophila. Proc Biol Sci 273:939–947
Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3:442–455
Biteau B, Karpac J, Supoyo S, DeGennaro M, Lehmann R, Jasper H (2010) Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS Genet 6:e1001159
Biteau B, Hochmuth CE, Jasper H (2011) Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 9:402–411
Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, Rando TA (2007) Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317:807–810
Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA (2008) A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis. Cell Stem Cell 2:50–59
Buchon N, Broderick NA, Chakrabarti S, Lemaitre B (2009) Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev 23:2333–2344
Bufalino MR, DeVeale B, van der Kooy D (2013) The asymmetric segregation of damaged proteins is stem cell-type dependent. J Cell Biol 201:523–530
Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705
Cargill SL, Carey JR, Muller HG, Anderson G (2003) Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell 2:185–190
Casali A, Batlle E (2009) Intestinal stem cells in mammals and Drosophila. Cell Stem Cell 4:124–127
Choi NH, Kim JG, Yang DJ, Kim YS, Yoo MA (2008) Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor. Aging Cell 7:318–334
Conboy IM, Rando TA (2005) Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle 4:407–410
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764
Crawford D, Libina N, Kenyon C (2007) Caenorhabditis elegans integrates food and reproductive signals in lifespan determination. Aging Cell 6:715–721
Decotto E, Spradling AC (2005) The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. Dev Cell 9:501–510
Dhawan J, Rando TA (2005) Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment. Trends Cell Biol 15:666–673
Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D, Lam JS, Ailles LE, Wong M et al (2009) Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:780–783
Drummond-Barbosa D, Spradling AC (2001) Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol 231:265–278
Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C et al (2008) The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 3:e2020
Flatt T, Min KJ, D’Alterio C, Villa-Cuesta E, Cumbers J, Lehmann R, Jones DL, Tatar M (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proc Natl Acad Sci U S A 105:6368–6373
Fox DT, Spradling AC (2009) The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage. Cell Stem Cell 5:290–297
Fuchs E (2009) The tortoise and the hair: slow-cycling cells in the stem cell race. Cell 137:811–819
Fuentealba LC, Eivers E, Geissert D, Taelman V, De Robertis EM (2008) Asymmetric mitosis: unequal segregation of proteins destined for degradation. Proc Natl Acad Sci U S A 105:7732–7737
Gonczy P, DiNardo S (1996) The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis. Development 122:2437–2447
Guarente L, Picard F (2005) Calorie restriction–the SIR2 connection. Cell 120:473–482
Gunes C, Rudolph KL (2013) The role of telomeres in stem cells and cancer. Cell 152:390–393
Ha EM, Oh CT, Bae YS, Lee WJ (2005) A direct role for dual oxidase in Drosophila gut immunity. Science 310:847–850
Hochmuth CE, Biteau B, Bohmann D, Jasper H (2011) Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell 8:1–12
Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–366
Hsu HJ, Drummond-Barbosa D (2009) Insulin levels control female germline stem cell maintenance via the niche in Drosophila. Proc Natl Acad Sci U S A 106:1117–1121
Hsu HJ, LaFever L, Drummond-Barbosa D (2008) Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila. Dev Biol 313:700–712
Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:693–706
Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, Nomiyama K, Hosokawa K, Sakurada K, Nakagata N et al (2004) Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431:997–1002
Jasper H, Jones DL (2010) Metabolic regulation of stem cell behavior and implications for aging. Cell Metab 12:561–565
Jiang H, Patel PH, Kohlmaier A, Grenley MO, McEwen DG, Edgar BA (2009) Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137:1343–1355
Jones DL, Rando TA (2011) Emerging models and paradigms for stem cell ageing. Nat Cell Biol 13:506–512
Kalaany NY, Sabatini DM (2009) Tumours with PI3K activation are resistant to dietary restriction. Nature 458:725–731
Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11:453–465
Kapuria S, Karpac J, Biteau B, Hwangbo D, Jasper H (2012) Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage. PLoS Genet 8(11):e1003045
Katewa SD, Kapahi P (2010) Dietary restriction and aging, 2009. Aging Cell 9:105–112
LaFever L, Drummond-Barbosa D (2005) Direct control of germline stem cell division and cyst growth by neural insulin in Drosophila. Science 309:1071–1073
LaFever L, Feoktistov A, Hsu HJ, Drummond-Barbosa D (2010) Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary. Development 137:2117–2126
Lamba DA, Gust J, Reh TA (2009) Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4:73–79
Lapouge G, Youssef KK, Vokaer B, Achouri Y, Michaux C, Sotiropoulou PA, Blanpain C (2011) Identifying the cellular origin of squamous skin tumors. Proc Natl Acad Sci U S A 108:7431–7436
Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, Wu H, Kornblum HI (2011) Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell 8:59–71
Li L, Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327:542–545
Lindvall O, Barker RA, Brustle O, Isacson O, Svendsen CN (2012) Clinical translation of stem cells in neurodegenerative disorders. Cell Stem Cell 10:151–155
Liu J, Cao L, Chen J, Song S, Lee IH, Quijano C, Liu H, Keyvanfar K, Chen H, Cao LY et al (2009) Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459:387–392
Mair W, McLeod CJ, Wang L, Jones DL (2010) Dietary restriction enhances germline stem cell maintenance. Aging Cell 9(5):916–918
Margolis J, Spradling A (1995) Identification and behavior of epithelial stem cells in the Drosophila ovary. Development 121:3797–3807
Mason JB, Cargill SL, Anderson GB, Carey JR (2009) Transplantation of young ovaries to old mice increased life span in transplant recipients. J Gerontol A Biol Sci Med Sci 64:1207–1211
McLeod CJ, Wang L, Wong C, Jones DL (2010) Stem cell dynamics in response to nutrient availability. Curr Biol 20:2100–2105
Melton C, Judson RL, Blelloch R (2010) Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463:621–626
Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, Sevillano M, Hernando-Momblona X, da Silva-Diz V, Munoz P et al (2011) The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell 8:511–524
Micchelli CA, Perrimon N (2006) Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439:475–479
Miyamoto K, Araki KY, Naka K, Arai F, Takubo K, Yamazaki S, Matsuoka S, Miyamoto T, Ito K, Ohmura M et al (2007) Foxo3a is essential for maintenance of the hematopoietic stem cell pool. Cell Stem Cell 1:101–112
Ohlstein B, Spradling A (2006) The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439:470–474
Owusu-Ansah E, Banerjee U (2009) Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature 461(7263):537–541
Pan L, Chen S, Weng C, Call G, Zhu D, Tang H, Zhang N, Xie T (2007) Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. Cell Stem Cell 1:458–469
Pinkston JM, Garigan D, Hansen M, Kenyon C (2006) Mutations that increase the life span of C. elegans inhibit tumor growth. Science 313:971–975
Radtke F, Clevers H (2005) Self-renewal and cancer of the gut: two sides of a coin. Science 307:1904–1909
Rando TA (2006) Stem cells, ageing and the quest for immortality. Nature 441:1080–1086
Renault VM, Rafalski VA, Morgan AA, Salih DA, Brett JO, Webb AE, Villeda SA, Thekkat PU, Guillerey C, Denko NC et al (2009) FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5:527–539
Rera M, Bahadorani S, Cho J, Koehler CL, Ulgherait M, Hur JH, Ansari WS, Lo T Jr, Jones DL, Walker DW (2011) Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab 14:623–634
Rera M, Clark RI, Walker DW (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A 109:21528–21533
Robinton DA, Daley GQ (2012) The promise of induced pluripotent stem cells in research and therapy. Nature 481:295–305
Rock JR, Gao X, Xue Y, Randell SH, Kong YY, Hogan BL (2011) Notch-dependent differentiation of adult airway basal stem cells. Cell Stem Cell 8:639–648
Rossi DJ, Jamieson CH, Weissman IL (2008) Stems cells and the pathways to aging and cancer. Cell 132:681–696
Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN, Wagers AJ, Franklin RJ (2012) Rejuvenation of regeneration in the aging central nervous system. Cell Stem Cell 10:96–103
Rudolph KL, Hartmann D, Opitz OG (2009) Telomere dysfunction and DNA damage checkpoints in diseases and cancer of the gastrointestinal tract. Gastroenterology 137:754–762
Sancho R, Nateri AS, de Vinuesa AG, Aguilera C, Nye E, Spencer-Dene B, Behrens A (2009) JNK signalling modulates intestinal homeostasis and tumourigenesis in mice. EMBO J 28:1843–1854
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469:415–418
Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8:703–713
Shcheprova Z, Baldi S, Frei SB, Gonnet G, Barral Y (2008) A mechanism for asymmetric segregation of age during yeast budding. Nature 454:728–734
Shea KL, Xiang W, LaPorta VS, Licht JD, Keller C, Basson MA, Brack AS (2010) Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration. Cell Stem Cell 6:117–129
Simons BD, Clevers H (2011) Strategies for homeostatic stem cell self-renewal in adult tissues. Cell 145:851–862
Singh SR, Liu W, Hou SX (2007) The adult Drosophila malpighian tubules are maintained by multipotent stem cells. Cell Stem Cell 1:191–203
Smith J, Ladi E, Mayer-Proschel M, Noble M (2000) Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cell. Proc Natl Acad Sci U S A 97:10032–10037
Sun P, Quan Z, Zhang B, Wu T, Xi R (2010) TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation. Development 137:2461–2469
Takashima S, Mkrtchyan M, Younossi-Hartenstein A, Merriam JR, Hartenstein V (2008) The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling. Nature 454:651–655
Toledano H, D’Alterio C, Czech B, Levine E, Jones DL (2012) The let-7-Imp axis regulates aging of the Drosophila testis stem cell niche. Nature 485(7400):605–610
Tothova Z, Gilliland DG (2007) FoxO transcription factors and stem cell homeostasis: insights from the hematopoietic system. Cell Stem Cell 1:140–152
Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C et al (2007) FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128:325–339
Tsatmali M, Walcott EC, Crossin KL (2005) Newborn neurons acquire high levels of reactive oxygen species and increased mitochondrial proteins upon differentiation from progenitors. Brain Res 1040:137–150
Ueishi S, Shimizu H, H Inoue Y (2009) Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila. Cell Struct Funct 34:61–69
van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71:241–260
Voog J, Jones DL (2010) Stem cells and the niche: a dynamic duo. Cell Stem Cell 6:103–115
Wagers AJ, Conboy IM (2005) Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122:659–667
Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, Imakado S, Kotsuji T, Otsuka F, Roop DR et al (2003) Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet 35:238–245
Wang MC, O’Rourke EJ, Ruvkun G (2008) Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:957–960
White AC, Tran K, Khuu J, Dang C, Cui Y, Binder SW, Lowry WE (2011) Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A 108:7425–7430
Yang J, Kalhan SC, Hanson RW (2009) What is the metabolic role of phosphoenolpyruvate carboxykinase? J Biol Chem 284:27025–27029
Yilmaz ÖH, Katajisto P, Lamming DW, Gültekin Y, Bauer-Rowe KE, Sengupta S, Birsoy K, Dursun A, Yilmaz VO, Selig M et al (2012) mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature 486(7404):490–495
Youssef KK, Van Keymeulen A, Lapouge G, Beck B, Michaux C, Achouri Y, Sotiropoulou PA, Blanpain C (2010) Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol 12:299–305
Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K et al (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med 18(4):618–623
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The author is supported by the National Institute on Aging (NIH RO1 AG028127) and the National Institute of General Medical Sciences (NIH RO1 GM100196).
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Jasper, H. (2015). Stem Cell Aging: An Overview. In: Geiger, H., Jasper, H., Florian, M. (eds) Stem Cell Aging: Mechanisms, Consequences, Rejuvenation. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1232-8_1
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