Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline

Xiao, Yu; Yang, Mingzhi; Xiao, Ye; Guo, Qi; Huang, Yan; Li, Chang Jun; Cai, Dongsheng; Luo, Xiang

doi:10.1016/j.cmet.2020.01.002

Cited by 79 publications

(103 citation statements)

References 56 publications

(71 reference statements)

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“…As revealed previously, htNSC are Sox2 positive, mostly located in the hypothalamic third ventricle wall and the MBH parenchyma ( Li et al, 2012 , 2014 ; Zhang et al, 2017 ; Cai & Khor, 2019 ; Tang et al, 2020 ; Xiao et al, 2020 ). Consistently, the cerebroventricular system has been increasingly recognized for the role of neuropeptide in physiological regulation ( Noble et al, 2018 ).…”

Section: Resultssupporting

confidence: 72%

“…To answer this question, we generated a lentivirus expressing PTMS-HA driven by Sox2 promoter, using a lentiviral promoter system which is effective for inducing gene expression specifically in Sox2positive cells which belong to the populations of NSCs and early offspring before terminal differentiation. This method has been established in the literature and our previous studies (Li et al, 2012(Li et al, , 2014Zhang et al, 2017;Tang et al, 2020;Xiao et al, 2020), as we repeatedly confirmed that this Sox2 promoter-driven lentivirus delivered an ectopic protein such as GFP specifically into Sox2positive cells without targeting neurons. We delivered these lentiviruses into the mediobasal hypothalamus (MBH) of mice; at 1 wk after injection, hypothalamic sections were made for examining the expression of the delivered gene.…”

Section: Ptms Transfer From Htnsc To Neurons In the Hypothalamussupporting

confidence: 71%

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Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

Tang

Cai

2020

Life Sci. Alliance

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This study reports that parathymosin (PTMS) is secreted by hypothalamic stem/progenitor cells (htNSC) to inhibit senescence of recipient cells such as fibroblasts. Upon release, PTMS is rapidly transferred into the nuclei of various cell types, including neuronal GT1-7 cells and different peripheral cells, and it is effectively transferred into neuronal nuclei in various brain regions in vivo. Notably, brain neurons also produce and release PTMS, and because neuronal populations are large, they are important for maintaining PTMS in the cerebrospinal fluid which is further transferable into the blood. Compared with several other brain regions, the hypothalamus is stronger for long-distance PTMS transfer, supporting a key hypothalamic role in this function. In physiology, aging is associated with declines in PTMS production and transfer in the brain, and ptms knockdown in the hypothalamus versus hippocampus were studied showing different contributions to neurobehavioral physiology. In conclusion, the brain is an endocrine organ through secretion and nuclear transfer of PTMS, and the hypothalamus–brain orchestration of this function is protective in physiology and counteractive against aging-related disorders.

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Section: Resultssupporting

confidence: 72%

Section: Ptms Transfer From Htnsc To Neurons In the Hypothalamussupporting

confidence: 71%

Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

Tang

Cai

2020

Life Sci. Alliance

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“…Similarly, the diminished neuroendocrine function of the hypothalamus is associated with the cognitive decline with advancing age and a consequence of loss of hypothalamic NSC functions (Zhang et al, 2013). This loss of function is a result of the NSC senescence of hypothalamic NSCs (Xiao et al, 2020). Using primary neurospheres of murine hypothalamic NSCs, the long non-coding RNA Gm31629 was found to be reduced with aging and function as a biomarker of cellular senescence through a stabilized interaction with Y-box1 (YB-1) protein (Xiao et al, 2020).…”

Section: Novel Therapeutics For Brain Agingmentioning

confidence: 99%

“…This loss of function is a result of the NSC senescence of hypothalamic NSCs (Xiao et al, 2020). Using primary neurospheres of murine hypothalamic NSCs, the long non-coding RNA Gm31629 was found to be reduced with aging and function as a biomarker of cellular senescence through a stabilized interaction with Y-box1 (YB-1) protein (Xiao et al, 2020). Based on this, nuclear magnetic resonance (NMR) was applied to understand how Gm31629 conferred stability to YB-1 to then perform a molecular docking and virtual screen of a library of natural small molecule compounds that identified theaflavin 3-gallate (TF2A; Xiao et al, 2020).…”

Section: Novel Therapeutics For Brain Agingmentioning

confidence: 99%

Stem Cells of the Aging Brain

Nicaise

Willis

Crocker

et al. 2020

Front. Aging Neurosci.

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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 current in vivo and in vitro models 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 established in vivo animal and in vitro human 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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“…Quantitative PCR analysis was performed as described previously (Xiao et al, 2020). Briefly, we extracted RNA from cells using Trizol reagent (Takara).…”

Section: Real-time Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis

Peng

Wen

2020

Front. Cell Dev. Biol.

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Autosomal dominant osteopetrosis type II (ADO II), characterized by increased bone mass and density, is caused by mutations in the chloride channel 7 ( CLCN7 ) gene. In this study, a novel missense variant in CLCN7 (c.1678A > G; p.Met560Val) was identified in three symptomatic subjects and one carrier of a Chinese family with ADO II. Notably, bone formation markers, including osteocalcin and total procollagen type N-terminal propeptide, have increased or presented at the upper limit of the normal range in the three patients. Serum factors secreted by osteoclast lineage cells and affecting the CD31 hi EMCN hi vessel formation, such as tartrate-resistant acid phosphatase 5b, platelet-derived growth factor-BB, vascular endothelial growth factor, and SLIT3, had a higher expression in three ADO II subjects than in 15 healthy age-matched and sex-matched controls. Moreover, the conditioned medium was obtained from preosteoclast induced from the ADO II patients’ peripheral blood mononuclear cells. It was found to promote the CD31 hi EMCN hi vessel formation of human microvascular endothelial cells and osteogenic differentiation of bone marrow-derived stem cells. Taken together, our finding revealed a novel CLCN7 variant associated with ADO II and suggested that the sclerotic bone was potentially associated with the increase of the CD31 hi EMCN hi vessel formation and bone formation.

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Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline

Cited by 79 publications

References 56 publications

Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

Stem Cells of the Aging Brain

A Novel Variant in CLCN7 Regulates the Coupling of Angiogenesis and Osteogenesis

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