The Role of the Microenvironmental Niche in Declining Stem-Cell Functions Associated with Biological Aging

DeCarolis, Nathan A.; Kirby, Elizabeth D.; Wyss‐Coray, Tony; Palmer, Theo D.

doi:10.1101/cshperspect.a025874

Cited by 46 publications

(23 citation statements)

References 84 publications

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“…Many physiological and pathological events are able to control neurogenesis by modulating proliferation, differentiation, maturation and integration of newborn neurons into the existing circuitry (Zhao, Deng & Gage, 2008). This balance can be disrupted by chronic stress (Egeland, Zunszain & Pariante, 2015) depression (Mahar et al, 2014), aging (DeCarolis et al, 2015), and neurodegenerative diseases (Winner & Winkler, 2015). …”

Section: Introductionmentioning

confidence: 99%

Harmine stimulates proliferation of human neural progenitors

Dakic

Maciel

Drummond

et al. 2016

PeerJ

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Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

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Section: Introductionmentioning

confidence: 99%

Harmine stimulates proliferation of human neural progenitors

Dakic

Maciel

Drummond

et al. 2016

PeerJ

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“…However, this result might rely on the assumption that stem cell replication is constant over the life time but for the periods of treatment. While this assumption is a good approximation for skin tissue, in which stem cell replication is widely conserved at all ages [12], other organs exhibit a decrease of the stem cell replication rate with age [1]. For example, hematopoietic stem cells lose power in the course of ageing [13,14].…”

Section: Resultsmentioning

confidence: 99%

“…Without DNA damage, stem cell activity could be maintained on a level that guarantees better homeostasis of the organism. However, stem-cell function declines over time and is associated with ageing [1]. There is increasing evidence that the process of decline of stem-cell function can be reverted by transfer of blood from younger individuals in liver [2] and brain [3].…”

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confidence: 99%

Estimation of the cancer risk induced by rejuvenation therapy with young blood and treatment recommendations

Meyer‐Hermann

2018

Preprint

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In recent years the transfer of blood from young to old individuals was shown to bear the potential of rejuvenation of stem cell activity. While this process might increase life expectancy by prolonging functionality of organs, higher cell replication rates bear also the risk of cancer. The extent of this risk is not known.While it is difficult to evaluate this cancer risk in experiments, this is possible with a mathematical model for tissue homeostasis by stem cell replication and associated cancer risk. The model suggests that young blood treatments can induce a substantial delay of organ failure with only minor increase in cancer risk. The benefit of rejuvenation therapy as well as the impact on cancer risk depend on the biological age at the time of treatment and on the overall cell turnover rate of the organs. Different organs have to be considered separately in the planning of the systemic treatment. In particular, the model predicts that the treatment schedules successfully applied in mice are not directly transferable to humans and guidelines for successful protocols are proposed. The model presented here may be used as a guidance for the development of treatment protocols. Additional informationThere is NO competing interests.

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“…Many physiological and pathological events are able to control neurogenesis by modulating proliferation, differentiation, maturation and integration of newborn neurons into the existing circuitry 1 . This balance can be disrupted by chronic stress 2 , depression 3 , aging 4 , and neurodegenerative diseases 5 .…”

Section: Introductionmentioning

confidence: 99%