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Aging and disease    2019, Vol. 10 Issue (4) : 871-882     DOI: 10.14336/AD.2018.1119
Review |
Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging
Min-jun Wang1, Jiajia Chen1, Fei Chen1, Qinggui Liu1, Yu Sun1, Chen Yan1, Tao Yang1, Yiwen Bao1,2, Yi-Ping Hu1,*
1Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, Shanghai 200433, China
2Department of Diagnostic radiology, University of Hong Kong, Hong Kong 999077, China
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Abstract  

Although aging is a physiological process, it has raised interest in the science of aging and rejuvenation because of the increasing burden on the rapidly aging global population. With advanced age, there is a decline in homeostatic maintenance and regenerative responsiveness to the injury of various tissues, thereby contributing to the incidence of age-related diseases. The primary cause of the functional declines that occur along with aging is considered to be the exhaustion of stem cell functions in their corresponding tissues. Age-related changes in the systemic environment, the niche, and stem cells contribute to this loss. Thus, the reversal of stem cell aging at the cellular level might lead to the rejuvenation of the animal at an organismic level and the prevention of aging, which would be critical for developing new therapies for age-related dysfunction and diseases. Here, we will explore the effects of aging on stem cells in different tissues. The focus of this discussion is on pro-youth interventions that target intrinsic stem cell properties, environmental niche component, systemic factors, and senescent cellular clearance, which are promising for developing strategies related to the reversal of aged stem cell function and optimizing tissue repair processes.

Keywords Rejuvenation      Stem cell aging      Tissue homeostasis      Regenerative impairment      Stem cell niche      Systemic environment     
Corresponding Authors: Hu Yi-Ping   
About author:

These authors contributed equally to this work.

Just Accepted Date: 26 November 2018   Issue Date: 01 August 2019
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Min-jun Wang
Jiajia Chen
Fei Chen
Qinggui Liu
Yu Sun
Chen Yan
Tao Yang
Yiwen Bao
Yi-Ping Hu
Cite this article:   
Min-jun Wang,Jiajia Chen,Fei Chen, et al. Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging[J]. Aging and disease, 2019, 10(4): 871-882.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.1119     OR     http://www.aginganddisease.org/EN/Y2019/V10/I4/871
Figure 1.  Summary of the underlying mechanisms contributing to the age-related changes in tissue-specific stem cells

During aging, stem cells are controlled by intrinsic effectors including DNA damage accumulation, epigenetic changes, abnormal genes expression, and dysregulated cell signaling pathways, as well controlled by extrinsic mechanisms that are consist of stem cell niche and systemic environment. With these intrinsic effectors and cell-extrinsic regulations, the aged stem cells display numbers changes, limited self-renewal, senescence, skewing differentiation, and impaired regeneration.

Intervening approachTarget cellMechanismRejuvenation on functionReferences
Fgfr1 inhibitor SU5402 or Spry1 overexpressionMuSCsreducing FGF signalingloss of quiescence, regenerative capacity[24]
Fibronection injectionMuSCsrescue FAK signalingproliferative and myogenic potential[78]
TS2/16MuSCsactivation of β1-integrin/FGFRregenerative capacity[17]
Tyr AG 490MuSCsinhibition of JAK/STATsatellite cell number; self-renewal; regenerative capacity[70]
5,15 diphenylporphrineMuSCsinhibition of JAK/STATsatellite cell number; self-renewal; regenerative capacity[70]
Sodium salicylateMuSCsinhibition of NF-κB signalingregenerative capacity[79]
SB-505124NSCsblockade of TGFβ signalingproliferation of stem cells; neurogenesis[82]
Lateral ventricle choroid plexus (LVCP) secretomeNSCsunknownproliferation, self-renewal, and differentiation[32]
Loss of Dkk1NSCsincrease of Wnt activityself-renewal; number of neuronal progenitors; neurogenesis[83]
Rantes knockoutHSCsdecreased mTOR activitymyeloid skewing; engraftment potential[80]
Inactivation of the gene encoding Fbxw7HSCsactivation of Notch signalingHSCs numbers[81]
Table 1  Rejuvenation of tissue-specific stem cells via therapeutic molecules on their niche.
Intervening approachTarget cellMechanismRejuvenation on functionReferences
Frizzled-related protein 3 (sFRP3) incubationMuSCssuppression of Wnt signalingproliferative potential; muscle regeneration[22]
Dickkopf-1 (Dkk1) injectionMuSCssuppression of Wnt signalingmuscle regeneration[22]
TGF-beta receptor kinase inhibitorMuSCsattenuating TGFβ signllingregenerative potential[21]
Recombinant GDF11 injectionMuSCsunknownregenerative potential[35]
OxytocinMuSCsactivation of MAPK/ERK signalingMuSC activation and proliferation; regenerative potential[91]
Recombinant GDF11 injectionNSCsactivation of TGFβ signalingself-renewal; differentiation potential; neurogenesis[36]
GnRH I injectionNSCsunknownneuronesis; cognitive function[87]
CCL11-specific neutralizing antibodyNSCsunknownneuronesis; cognitive function[37]
N-acetylcysteine incubationMSCsScavenging reactive oxygen species (ROS)aging phenotypes[85]
4-hydroxytamoxifen (4-OHT) injectionSkinblockade of NF-κBage-associated gene expression; proliferation[86]
Recombinant GDF11 injectionRenal Epithelial cellUpregulating ERK1/2 pathwayproliferative capacity; renal repair[93]
Table 2  Intervention in systemic environment to rejuvenate function of tissue-specific stem cells.
[1] Sánchez Alvarado A, Yamanaka S (2014). Rethinking differentiation: stem cells, regeneration, and plasticity. Cell, 157: 110-119
[2] Goodell MA, Rando TA (2015). Stem cells and healthy aging. Science, 350: 1199-1204
[3] Schultz MB, Sinclair DA (2016). When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development, 143: 3-14
[4] Oh J, Lee YD, Wagers AJ (2014). Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med, 20: 870-880
[5] Honoki K (2017). Preventing aging with stem cell rejuvenation: Feasible or infeasible? World J Stem Cells, 9: 1-8
[6] Neves J, Sousa-Victor P, Jasper H (2017). Rejuvenating Strategies for Stem Cell-Based Therapies in Aging. Cell Stem Cell, 20: 161-175
[7] Ho TT, Warr MR, Adelman ER, Lansinger OM, Flach J, Verovskaya EV, et al. (2017). Autophagy maintains the metabolism and function of young and old stem cells. Nature, 543: 205-210
[8] Barker N, Bartfeld S, Clevers H (2010). Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell, 7: 656-670
[9] Collins CA, Zammit PS, Ruiz AP, Morgan JE, Partridge TA (2007). A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells, 25: 885-894
[10] Maslov AY, Barone TA, Plunkett RJ, Pruitt SC (2004). Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci, 24: 1726-1733
[11] Nishimura EK (2011). Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res, 24: 401-410
[12] Paul C, Nagano M, Robaire B (2013). Aging results in molecular changes in an enriched population of undifferentiated rat spermatogonia. Biol Reprod, 89: 147
[13] Florian MC, Dörr K, Niebel A, Daria D, Schrezenmeier H, Rojewski M, et al. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell Stem Cell, 10: 520-530
[14] Florian MC, Nattamai KJ, Dörr K, Marka G, Uberle B, Vas V, et al. (2013). A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature, 503: 392-396
[15] Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G (2011). Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med, 208: 2691-2703
[16] Bernet JD, Doles JD, Hall JK, Kelly Tanaka K, Carter TA, Olwin BB (2014). p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice. Nat Med, 20: 265-271
[17] Rozo M, Li L, Fan CM (2016). Targeting β1-Integrin Signaling Enhances Regeneration in Aged and Dystrophic Muscle in Mice. Nat Med, 22: 889-896
[18] Nishimura EK, Granter SR, Fisher DE (2005). Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche. Science, 307: 720-724
[19] Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, Weissman IL (2005). Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A, 102: 9194-9199
[20] Lichtman MA, Rowe JM (2004). The relationship of patient age to the pathobiology of the clonal myeloid diseases. Semin Oncol, 31: 185-197
[21] Carlson ME, Conboy MJ, Hsu M, Barchas L, Jeong J, Agrawal A, et al. (2009). Relative roles of TGF-beta1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell, 8: 676-689
[22] Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, et al. (2007). Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science, 317: 807-810
[23] Encinas JM, Michurina TV, Peunova N, Park JH, Tordo J, Peterson DA, et al. (2011). Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell, 8: 566-579
[24] Chakkalakal JV, Jones KM, Basson MA, Brack AS (2012). The aged niche disrupts muscle stem cell quiescence. Nature, 490: 355-360
[25] Blau HM, Cosgrove BD, Ho AT (2015). The central role of muscle stem cells in regenerative failure with aging. Nat Med, 21: 854-862
[26] Choudhary B, Karande AA, Raghavan SC (2012). Telomere and telomerase in stem cells: relevance in ageing and disease. Front Biosci (Schol Ed), 4: 16-30
[27] Wang J, Sun Q, Morita Y, Jiang H, Gross A, Lechel A, et al. (2012). A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell, 148: 1001-1014
[28] Beerman I, Rossi DJ (2014). Epigenetic regulation of hematopoietic stem cell aging. Exp Cell Res, 329: 192-199
[29] Cosgrove BD, Gilbert PM, Porpiglia E, Mourkioti F, Lee SP, Corbel SY, et al. (2014). Rejuvenation of the muscle stem cell population restores strength to injured aged muscles. Nat Med, 20: 255-264
[30] Doles J, Storer M, Cozzuto L, Roma G, Keyes WM (2012). Age-associated inflammation inhibits epidermal stem cell function. Genes Dev, 26: 2144-2153
[31] Keyes BE, Segal JP, Heller E, Lien WH, Chang CY, Guo X, et al. (2013). Nfatc1 orchestrates aging in hair follicle stem cells. Proc Natl Acad Sci U S A, 110: E4950-4959
[32] Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F (2016). Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells. Cell Stem Cell, 19: 643-652
[33] Kang E, Wang X, Tippner-Hedges R, Ma H, Folmes CD, Gutierrez NM, et al. (2016). Age-Related Accumulation of Somatic Mitochondrial DNA Mutations in Adult-Derived Human iPSCs. Cell Stem Cell, 18: 625-636
[34] Cheung TH, Rando TA (2013). Molecular regulation of stem cell quiescence. Nat Rev Mol Cell Biol, 14: 329-340
[35] Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, et al. (2014). Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science, 344: 649-652
[36] Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, et al. (2014). Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science, 344: 630-634
[37] Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, et al. (2011). The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477: 90-94
[38] Henry CJ, Marusyk A, DeGregori J (2011). Aging-associated changes in hematopoiesis and leukemogenesis: what's the connection? Aging (Albany NY), 3: 643-656
[39] Sousa-Victor P, García-Prat L, Serrano AL, Perdiguero E, Muñoz-Cánoves P (2015). Muscle stem cell aging: regulation and rejuvenation. Trends Endocrinol Metab, 26: 287-296
[40] Bishop NA, Lu T, Yankner BA (2010). Neural mechanisms of ageing and cognitive decline. Nature, 464: 529-535
[41] McGinnis SL, Moore J (2006). The impact of the aging population on the health workforce in the United States--summary of key findings. Cah Sociol Demogr Med, 46: 193-220
[42] Merlos-Suárez A, Barriga FM, Jung P, Iglesias M, Céspedes MV, Rossell D, et al. (2011). The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell, 8: 511-524
[43] Inomata K, Aoto T, Binh NT, Okamoto N, Tanimura S, Wakayama T, et al. (2009). Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell, 137: 1088-1099
[44] Beerman I, Seita J, Inlay MA, Weissman IL, Rossi DJ (2014). Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell, 15: 37-50
[45] Rübe CE, Fricke A, Widmann TA, Fürst T, Madry H, Pfreundschuh M, et al. (2011). Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS ONE, 6: e17487
[46] Rossi DJ, Seita J, Czechowicz A, Bhattacharya D, Bryder D, Weissman IL (2007). Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging. Cell Cycle, 6: 2371-2376
[47] Matsumura H, Mohri Y, Binh NT, Morinaga H, Fukuda M, Ito M, et al. (2016). Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science, 351: aad4395
[48] Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, et al. (2006). Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med, 12: 446-451
[49] Freitas AA, de Magalhães JP (2011). A review and appraisal of the DNA damage theory of ageing. Mutat Res, 728: 12-22
[50] Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, et al. (2012). The sirtuin SIRT6 regulates lifespan in male mice. Nature, 483: 218-221
[51] Sousa-Victor P, Ayyaz A, Hayashi R, Qi Y, Madden DT, Lunyak VV, et al. (2017). Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells. Cell Rep, 20: 2527-2537
[52] Flores I, Canela A, Vera E, Tejera A, Cotsarelis G, Blasco MA (2008). The longest telomeres: a general signature of adult stem cell compartments. Genes Dev, 22: 654-667
[53] Hosokawa K, MacArthur BD, Ikushima YM, Toyama H, Masuhiro Y, Hanazawa S, et al. (2017). The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age. Nat Commun, 8: 804
[54] Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC, et al. (2011). Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, 469: 102-106
[55] Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, et al. (2006). Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature, 443: 421-426
[56] Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, et al. (2006). Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature, 443: 448-452
[57] Nishino J, Kim I, Chada K, Morrison SJ (2008). Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell, 135: 227-239
[58] Sousa-Victor P, Gutarra S, García-Prat L, Rodriguez-Ubreva J, Ortet L, Ruiz-Bonilla V, et al. (2014). Geriatric muscle stem cells switch reversible quiescence into senescence. Nature, 506: 316-321
[59] García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J, Rebollo E, et al. (2016). Autophagy maintains stemness by preventing senescence. Nature, 529: 37-42
[60] Beerman I, Rossi DJ (2015). Epigenetic Control of Stem Cell Potential during Homeostasis, Aging, and Disease. Cell Stem Cell, 16: 613-625
[61] Beerman I, Bock C, Garrison BS, Smith ZD, Gu H, Meissner A, et al. (2013). Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging. Cell Stem Cell, 12: 413-425
[62] Liu L, Cheung TH, Charville GW, Hurgo BM, Leavitt T, Shih J, et al. (2013). Chromatin modifications as determinants of muscle stem cell quiescence and chronological aging. Cell Rep, 4: 189-204
[63] Schwörer S, Becker F, Feller C, Baig AH, Köber U, Henze H, et al. (2016). Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals. Nature, 540: 428-432
[64] Sun D, Luo M, Jeong M, Rodriguez B, Xia Z, Hannah R, et al. (2014). Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell, 14: 673-688
[65] Wahlestedt M, Norddahl GL, Sten G, Ugale A, Frisk MA, Mattsson R, et al. (2013). An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state. Blood, 121: 4257-4264
[66] Satoh Y, Yokota T, Sudo T, Kondo M, Lai A, Kincade PW, et al. (2013). The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. Immunity, 38: 1105-1115
[67] Gontier G, Iyer M, Shea JM, Bieri G, Wheatley EG, Ramalho-Santos M, et al. (2018). Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain. Cell Rep, 22: 1974-1981
[68] Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, et al. (2013). SIRT3 reverses aging-associated degeneration. Cell Rep, 3: 319-327
[69] Mohrin M, Shin J, Liu Y, Brown K, Luo H, Xi Y, et al. (2015). Stem cell aging. A mitochondrial UPR-mediated metabolic checkpoint regulates hematopoietic stem cell aging. Science, 347: 1374-1377
[70] Price FD, von Maltzahn J, Bentzinger CF, Dumont NA, Yin H, Chang NC, et al. (2014). Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat Med, 20: 1174-1181
[71] Tierney MT, Aydogdu T, Sala D, Malecova B, Gatto S, Puri PL, et al. (2014). STAT3 signaling controls satellite cell expansion and skeletal muscle repair. Nat Med, 20: 1182-1186
[72] 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
[73] Carlson ME, Suetta C, Conboy MJ, Aagaard P, Mackey A, Kjaer M, et al. (2009). Molecular aging and rejuvenation of human muscle stem cells. EMBO Mol Med, 1: 381-391
[74] Chen C, Liu Y, Liu Y, Zheng P (2009). mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal, 2:ra75
[75] Haller S, Kapuria S, Riley RR, O'Leary MN, Schreiber KH, Andersen JK, et al. (2017). mTORC1 Activation during Repeated Regeneration Impairs Somatic Stem Cell Maintenance. Cell Stem Cell, 21: 806-818
[76] Bjornsson CS, Apostolopoulou M, Tian Y, Temple S (2015). It takes a village: constructing the neurogenic niche. Dev Cell, 32: 435-446
[77] Scadden DT (2014). Nice neighborhood: emerging concepts of the stem cell niche. Cell, 157: 41-50
[78] Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E, Rozo M, et al. (2016). Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nat Med, 22: 897-905
[79] Oh J, Sinha I, Tan KY, Rosner B, Dreyfuss JM, Gjata O, et al. (2016). Age-associated NF-κS signaling in myofibers alters the satellite cell niche and restrains muscle stem cell function. Aging (Albany NY), 8: 2871-2896
[80] Ergen AV, Boles NC, Goodell MA (2012). Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood, 119: 2500-2509
[81] Kusumbe AP, Ramasamy SK, Itkin T, Mäe MA, Langen UH, Betsholtz C, et al. (2016). Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature, 532: 380-384
[82] Pineda JR, Daynac M, Chicheportiche A, Cebrian-Silla A, SiiFelice K, Garcia-Verdugo JM, et al. (2013). Vascular-derived TGF-β increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain. EMBO Mol Med, 5: 548-562
[83] Seib DR, Corsini NS, Ellwanger K, Plaas C, Mateos A, Pitzer C, et al. (2013). Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline. Cell Stem Cell, 12: 204-214
[84] 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
[85] Zhang DY, Pan Y, Zhang C, Yan BX, Yu SS, Wu DL, et al. (2013a). Wnt/β-catenin signaling induces the aging of mesenchymal stem cells through promoting the ROS production. Mol Cell Biochem, 374: 13-20
[86] Adler AS, Sinha S, Kawahara TL, Zhang JY, Segal E, Chang HY (2007). Motif module map reveals enforcement of aging by continual NF-kappaB activity. Genes Dev, 21: 3244-3257
[87] Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, et al. (2013b). Hypothalamic programming of systemic ageing involving IKK-β, NF-κD and GnRH. Nature, 497: 211-216
[88] Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, et al. (2014). Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med, 20: 659-663
[89] Rebo J, Mehdipour M, Gathwala R, Causey K, Liu Y, Conboy MJ, et al. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nat Commun, 22: 13363
[90] Liu A, Guo E, Yang J, Yang Y, Liu S, Jiang X, et al. (2018). Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy. Aging Cell, 17
[91] Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, et al. (2014). Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nat Commun, 5: 4082
[92] Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, et al. (2013). Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell, 153: 828-839
[93] Zhang Y, Li Q, Liu D, Huang Q, Cai G, Cui S, et al. (2016). GDF11 improves tubular regeneration after acute kidney injury in elderly mice. Sci Rep, 6: 34624
[94] Egerman MA, Cadena SM, Gilbert JA, Meyer A, Nelson HN, Swalley SE, et al. (2015). GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration. Cell Metab, 22: 164-174
[95] Hinken AC, Powers JM, Luo G1, Holt JA, Billin AN, Russell AJ (2016). Lack of evidence for GDF11 as a rejuvenator of aged skeletal muscle satellite cells. Aging Cell, 15: 582-584
[96] Poggioli T, Vujic A, Yang P, Macias-Trevino C, Uygur A, Loffredo FS, et al. (2016). Circulating Growth Differentiation Factor 11/8 Levels Decline with Age. Circ Res, 118: 29-37
[97] Schafer MJ, Atkinson EJ, Vanderboom PM, Kotajarvi B, White TA, Moore MM, et al. (2016). Quantification of GDF11 and Myostatin in Human Aging and Cardiovascular Disease. Cell Metab, 23: 1207-1215
[98] Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006). Cellular senescence in aging primates. Science, 311: 1257
[99] Jeyapalan JC, Ferreira M, Sedivy JM, Herbig U (2007). Accumulation of senescent cells in mitotic tissue of aging primates. Mech Ageing Dev, 128: 36-44
[100] Van Deursen JM (2014). The role of senescent cells in ageing. Nature, 509: 439-446
[101] Wang C, Jurk D, Maddick M, Nelson G, Martin-Ruiz C, von Zglinicki T (2009). DNA damage response and cellular senescence in tissues of aging mice. Aging Cell, 8: 311-323
[102] Neves J, Demaria M, Campisi J, Jasper H (2015). Of flies, mice, and men: evolutionarily conserved tissue damage responses and aging. Dev Cell, 32: 9-18
[103] Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479: 232-236
[104] Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. (2016). Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature, 530: 184-189
[105] Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354: 472-477
[106] Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, et al. (2016). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med, 22: 78-83
[107] Ogrodnik M, Miwa S, Tchkonia T, Tiniakos D, Wilson CL, Lahat A, et al. (2017). Cellular senescence drives age-dependent hepatic steatosis. Nat Commun, 8: 15691
[108] Roos CM, Zhang B, Palmer AK, Ogrodnik MB, Pirtskhalava T, Thalji NM, et al. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 15: 973-977
[109] Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, et al. (2015). JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci U S A, 112: E6301-6310
[110] Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, et al. (2015). MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol, 17: 1049-1061
[111] Jeon OH, Kim C, Laberge RM, Demaria M, Rathod S, Vasserot AP, et al. (2017). Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nat Med, 23: 775-781
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