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A Review of Neurogenesis in the Aging Brain


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Posted 09 August 2018 - 10:23 AM


Neurogenesis is the process by which new neurons are created and then integrated into existing neural circuits. Does neurogenesis take place in the adult human brain? That is once again a subject for debate after two decades of consensus, with the arrival of solid evidence for the absence of neurogenesis in adult humans, even as other researchers continue to produce data showing that it does take place. This newfound uncertainty contrasts with the well-established presence of neurogenesis in adult mice, the species that is the focus of the vast majority of research on this topic.

This an important topic. Along with synaptic plasticity, it determines the ability of the brain to repair itself, to recover from the variety of losses that occur with aging or injury. If neurogenesis does occur in adult humans, then there may be comparatively straightforward approaches that can boost the operation of this process in order to slow the impact of aging. If it does not occur in adult humans, then the prospect of repairing the aging brain becomes harder and more distant.

The main reason behind the continuing interest in understanding the process of mammalian adult neurogenesis is the notion that similar processes might be involved in the human brain. Whether neurogenesis in humans exists has been investigated using several and distinct approaches that brought compelling evidence about the presence of adult hippocampal neurogenesis in human brains. Interestingly, two very recent - but opposing - publications brought back the debate concerning the existence of human adult neurogenesis. The first, using postmortem and fresh tissue, reported that there was no evidence of neurogenesis in humans after adolescence whatsoever, while the second demonstrated the exact opposite by showing that adult neurogenesis persists during life in humans, albeit with a small decrease with aging. Further exploration of this complex question is necessary in order to conclude on the processes underlying the timeline and the mechanisms of neurogenesis in humans.

Recently, in addition to the study of the overall process of neurogenesis, much effort has focused on deciphering the intrinsic regulation of stem cells in the brain, both in the hippocampus as well as the subventricular zone (SVZ) niche. Aging negatively affects neurogenesis by inducing a sharp and continuous decrease in cell production in both the SVZ and hippocampal neurogenic niches of the brain. With aging, activated neural stem cells (NSCs) lose their proliferative potential and become quiescent, but, remarkably, they can be reactivated to a certain extent upon stimulation, such as exercise or even seizure, indicating that NSC plasticity is preserved to a certain extent in the aged organism.

Because of the enormous consequences of aging on NSCs, a lot of effort has focused on identifying mechanisms that could potentially reset the aging clock. Systemic manipulations such as exercise, calorie restriction, and heterochronic blood transfer have demonstrated that it is possible to reactivate the intrinsic program in order to rejuvenate NSCs and, consequently, the brain. The delicate balance between NSC quiescence and activation is easily shifted depending on the different stimuli and could be used to better manipulate NSC fate in vitro and in vivo. Moreover, recent findings point to the conclusion that aging is not necessarily a permanent state, but could be malleable, and that finding ways to interfere in the cell intrinsic machinery in order to slow down or even reverse this process will be the challenge for years to come.

Link: https://doi.org/10.1...onb.2018.07.006


View the full article at FightAging




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