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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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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   
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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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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.
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