神经元寿命不受原有宿主寿命限制

神经元寿命不受原有宿主寿命限制

最近，意大利帕维亚大学和都灵大学的科学家通过实验证明，神经元的寿命不受生物最大寿命极限的限制，但它必须被移植到一个寿命更长的宿主身上，此时它的寿命能超过原来生物的寿命持续下去。相关论文发表在美国《国家科学院学报》上。

帕维亚大学的洛伦佐·马格雷希和同事利用一种脑细胞移植技术，在胸腺发育完成之前就把小鼠胚胎的小脑前体移植到另一种寿命更长的大鼠脑中，大鼠脑部正处于发育期。结果发现，移植到大鼠脑中的小鼠神经元能存活3年之久，这是小鼠平均寿命的两倍。

小脑神经元的树突、树突棘和突触会随正常老化而大量损失。马格雷希说：“我们移植了小鼠的浦肯野细胞（Purkinje Cell），以确定树突棘密度降低的速率究竟是跟小鼠还是大鼠自身的浦肯野细胞一样。”浦肯野细胞是从小脑皮质发出的唯一能传出冲动的神经元，有许多扩展分支。“结果表明，移植细胞的老化性树突棘损失速度变得更慢，和寿命更长的大鼠一样，相比于小鼠的老化而言，这达到了一种不受限制的水平。”

研究人员指出，这表明神经元的存活和老化是同时发生的，但却是各自独立的过程，延长机体寿命未必会导致大脑的最终耗竭。这为通过饮食、运动和药物干预等措施来延长生物寿命带来了更多希望。

马格雷希说，即使考虑了明显的种间差异，实验结果也能推广到人类和其他寿命更长的物种身上。通过延长平均生物寿命的方法来延长生命，不一定会出现生物在其寿命还很长时，脑中神经元就已所剩无几的情况。

研究小组还打算从蛋白质组水平实施宿主和移植细胞的显微切割，以研究是什么原因导致了树突棘损失变慢。马格雷希指出：“如果能发现某个或某些因素导致了这些变化，就有希望开发出更有效的药物，治疗所有病理性神经组织退化。这种退化开始于突触连接减少，在生物寿命结束前神经元就已经死了。”他们还在用不同种系的转基因小鼠实验异种移植，这些小鼠的老化路径已经被改变。

Separate lives: Neuronal and organismal lifespans decoupled

Replicati ve aging (also known as replicative senescence) causes mammalian cells to undergo a process of growth arrest dependent on telomeres (the shortening of repeated sequences at the ends of chromosomes). Neurons, on the other hand, are exempt from aging,and so the questi on of their actual lifespan has remained unanswered.Recently, however, scientists at the University of Pavia and the University of Turin demonstrated that neuronal lifespan is not limited by the organism's maximum lifespan but, remarkably, conti nues when transplanted in a longer-living host. The researchers accomplished this by transplanting embryonic mouse cerebellar precursors into the developing brain of longer-living rats, in which the grafted mouse neurons survived for up to three years – twice the average lifespan of the donor mice.

Dr. Lorenzo Magrassi discussed the challenges he and his colleagues, Dr. Ketty Leto and Dr. Ferdinando Rossi,encountered in their research."Cell transplantation into the developing rat brain is a technique that was originally developed by us and other research groups in the early nineties of the last century,"Magrassi tells Medical Xpress. "In recent years, we improved the protocol that, now standardized,allows reliable implantation rates with good survival rates." While not all implanted embryos develop into adult animals carrying a viable transplant, Magrassi adds,the percentage of those that do is sufficient to plan a long-term survival experiment involving roughly 100 such successfully-born animals.

In addressing these challenges, Magrassi says that together with the intrinsic bonus of studying cells inside the nervous system, which is immunoprivileged,they transplanted cells before development of the thymus (a specialized organ of the immune system) was complete. The latter can help induce immunological tolerance in the host to the engraft ed cells.

One remaining question is if their research can potentially be extended to determine whether or not a maximum lifespan exists for any postmitotic mammalian cells – Including neurons. "Similar techniques can, in principle,be extended to other organs containing perennial cells,"Magrassi notes, "but we don't have direct experience with injecting cells into organs outside of the central nervous system." Since the central nervous system is privileged compared to other organs that are more prone to immunological surveillance and attack, a major problem when transferring their experimental paradigm to other organs, he explains, could be an increase in immunological problems.

The scientists say their results suggest that neuronal survival and aging are coincidental but separable processes, thus increasing the hope that extending organismal lifespan by dietary,behavioral, and pharmacologic interventions will not necessarily result in a neuronally depleted brain. "Even after taking into account the obvious species differences, our results in rodents can be extrapolated by analogy to humans and other longerliving species where this sort of experiment is impossible," Magrassi explains. "Our fi ndings suggest that extending life by extending average organismal lifespan – a hallmark of all technologically advanced societi es – will not necessarily result in neuron-impoverished brains well before the longer-living individual dies." This bodes well for those studying life extension: Their eff orts are not intrinsically futi le, Magrassi notes, because in the absence of pathology, prolonging life span does not necessarily mean dementia due to widespread loss of neurons,as many people sti ll think.