Stem Cells of the Aging Brain

被引：58
作者：
Nicaise, Alexandra M. [1 ,2 ]
Willis, Cory M. [1 ,2 ]
Crocker, Stephen J. [3 ]
Pluchino, Stefano [1 ,2 ]
机构：
[1] Univ Cambridge, Dept Clin Neuroscien, Cambridge, England
[2] Univ Cambridge, NIHR Biomed Res Ctr, Cambridge, England
[3] Univ Connecticut, Sch Med, Dept Neurosci, Farmington, CT USA
来源：
FRONTIERS IN AGING NEUROSCIENCE | 2020年 / 12卷
基金：
英国医学研究理事会; 欧洲研究理事会; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;
关键词：
neural stem cells; aging; senescence; cell metabolism; mitochondria; disease modeling; senotherapeutics; MITOCHONDRIAL-DNA MUTATIONS; REPROGRAMMED HUMAN NEURONS; NEURAL PROGENITOR CELLS; COGNITIVE FUNCTION; SENESCENT CELLS; NEURODEGENERATIVE DISEASES; EXTRACELLULAR-MATRIX; SUBVENTRICULAR ZONE; SECRETORY PHENOTYPE; MULTIPLE-SCLEROSIS;
D O I：
10.3389/fnagi.2020.00247
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
The adult central nervous system (CNS) contains resident stem cells within specific niches that maintain a self-renewal and proliferative capacity to generate new neurons, astrocytes, and oligodendrocytes throughout adulthood. Physiological aging is associated with a progressive loss of function and a decline in the self-renewal and regenerative capacities of CNS stem cells. Also, the biggest risk factor for neurodegenerative diseases is age, and currentin vivoandin vitromodels of neurodegenerative diseases rarely consider this. Therefore, combining both aging research and appropriate interrogation of animal disease models towards the understanding of the disease and age-related stem cell failure is imperative to the discovery of new therapies. This review article will highlight the main intrinsic and extrinsic regulators of neural stem cell (NSC) aging and discuss how these factors impact normal homeostatic functions within the adult brain. We will consider establishedin vivoanimal andin vitrohuman disease model systems, and then discuss the current and future trajectories of novel senotherapeutics that target aging NSCs to ameliorate brain disease.
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页数：23
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