Evidence Against Adult Human Neurogenesis

The results here will cause some upheaval in the research community if verified, and will do doubt lead to considerable debate regardless of the outcome. For decades it is has been considered that neurogenesis, the production and integration of new neurons in the brain, continues past childhood, albeit at a lower rate. This is based largely on studies in mice, but also on a range of human evidence. The researchers here suggest that this is wrong, and in fact humans are not like mice in this regard: we do not generate new neurons at any detectable level as adults. This question of adult neurogenesis has great influence on the strategies adopted in the development of therapies that might enhance maintenance of the brain. This is a topic of considerable importance to the future of human rejuvenation: we are our brains, and damage and loss must be repaired in situ. If there are no naturally occurring mechanisms to achieve that goal in some or all of the brain, this suggests that the task will be that much harder to safely achieve.

One of the liveliest debates in neuroscience over the past half century surrounds whether the human brain renews itself by producing new neurons throughout life, and whether it may be possible to rejuvenate the brain by boosting its innate regenerative capacity. Now scientists have shown that in the human hippocampus - a region essential for learning and memory and one of the key places where researchers have been seeking evidence that new neurons continue to be born throughout the lifespan - neurogenesis declines throughout childhood and is undetectable in adults.

The findings present a challenge to a large body of research which has proposed that boosting the birth of new neurons could help to treat brain diseases such as Alzheimer's disease and depression. But the authors said it also opens the door to exciting new questions about how the human brain learns and adapts without a supply of new neurons, as in seen in mice and other animals. It was once neuroscientific dogma that the brain stops producing new neurons before birth. In the 1960s, experiments in rodents first suggested that new neurons could be born in the adult mammalian brain, but these results remained highly controversial until the 1980s, it was shown that new neurons are born and put to use throughout life in several parts of the songbird brain.

These findings launched a whole field of research. Much work has focused on a region of the hippocampus called the dentate gyrus (DG), where rodents produce newborn neurons throughout life that are thought to help them form distinct new memories, among other cognitive functions. Rodent studies have shown that DG neurogenesis declines with age, but is otherwise quite malleable - increasing with exercise, but decreasing with stress, for example - leading to popular claims that we can boost brain regeneration by living a healthy lifestyle. Beginning in the late '90s, a handful of studies reported evidence of adult neurogenesis in the human brain, either by estimating the birth dates of cells present in postmortem brain specimens or by labeling telltale molecular markers of newborn neurons or dividing neural stem cells. However, these findings, some of which were based on small numbers of brain samples, have remained controversial.

In the new study, researchers collected and analyzed samples of the human hippocampus. They analyzed changes in the number of newborn neurons and neural stem cells present in these samples, from before birth to adulthood, using a variety of antibodies to identify cells of different types and states of maturity, including neural stem cells and progenitors, newborn and mature neurons, and non-neuronal glial cells. The researchers also examined the cells they labeled based on their shape and structure - including imaging with high-resolution electron microscopy for a subset of tissue samples - in order to confirm their identity as neurons, neuronal stem cells, or glial cells.

The researchers found plentiful evidence of neurogenesis in the dentate gyrus during prenatal brain development and in newborns, observing an average of 1,618 young neurons per square millimeter of brain tissue at the time of birth. But the number of newborn cells sharply declined in samples obtained during early infancy: dentate gyrus samples from year-old infants contained fivefold fewer new neurons than was seen in samples from newborn infants. The decline continued into childhood, with the number of new neurons declining by 23-fold between one and seven years of age, followed by a further fivefold decrease by 13 years, at which point neurons also appeared more mature than those seen in samples from younger brains. The authors observed only about 2.4 new cells per square millimeter of DG tissue in early adolescence, and found no evidence of newborn neurons in any of the 17 adult post-mortem DG samples or in surgically extracted tissue samples from 12 adult patients with epilepsy.

Link: https://www.ucsf.edu/news/2018/03/409986/birth-new-neurons-human-hippocampus-ends-childhood


Well, fuck.

Posted by: TJ at March 8th, 2018 7:05 AM

My thoughts exactly. Makes me wonder if NSI-189 actually does stimulate neurogenesis in the hippocampus now..

Posted by: bmack500 at March 8th, 2018 9:47 AM

This does raise some questions.
For instance - is it viable to test Alzheimer's treatments in mice?

All the false positives we've had with treatments so far might have been caused by mice regenerating their hippocampus.
The way they create murine models of AD is they inject amyloid beta in their brains - and indeed, the peptides kill neurons in their brains just like they do in human brains.
Once the treatments are tested large quantities of the amyloids are removed. And mice can regenerate their hippocampus freely at that point as it seems and regain memory function.

It also points to the conclusion we might need to clear accumulated toxic material and hipppocampal neurons the brain to get a positive clinical outcome in a human - if that is the case I doubt an effective Alzheimer's therapy will be available to the public in the next 20 to 30 years - not with the current moods towards stem cell therapies.

Posted by: Anonymoose at March 8th, 2018 9:55 AM

edit : clear accumulated toxic material and regenerate hipppocampal neurons in the brain

Posted by: Anonymoose at March 8th, 2018 9:59 AM

Disappointing news, to say the least. Brain aging is truly daunting; I can imagine a sort of inverted(?) Tithonus scenario where one has a young, healthy body but 'screaming at the walls' Alzheimer's.

On a more positive note, I did come across something interesting - probably not news to most of the readers here, but news to me...
"This was a question that bugged me for a long time, is how is it that the mitochondria in neurons remain functional over so many decades where in virtually every other cell there's a turnover and the stem cells have got essentially a pristine population of mitochondria in them. It seems that in the case of neurons there is even mitochondrial transfer from the glial cells, which are essentially stem cells surrounding them, into the neurons..."

Posted by: CD at March 8th, 2018 11:38 AM

It mentions in the article that the can't spot any significant neural stem cells in the adult and possibly that's why there isn't any neurogenesis. It doesn't say anything about it not being possible for new cells to integrate by new interventions.

Posted by: Orion at March 8th, 2018 1:09 PM

I cannot understand the problem. Natural neurogenesis in human brain if one ever occurs is marginal.Rejuvenation biotechnology never relay on natural regeneration process, especially in postmitotic tissues. We will need to grow new neurons and implant them into the brain, or induce their regenerative ability in vivo via gene therapy.

Posted by: Ariel at March 8th, 2018 3:09 PM

I just looked up (googled) for other studies on adult hippocampal neurogenesis and found a recent study that contradicts the findings of the article under discussion here. Jan., 2018, American Journal of Pathology: Function and disfunction of adult hippocampal neurogenesis in regeneration and disease. So, I am not sure this issue is settled entirely yet.

Posted by: Biotechy at March 8th, 2018 4:07 PM


I'm worried about all the potentially viable therapies for AD we've passed over the decades because of the wrong assumptions made about the closeness of our brain to that of other mammals - I've had that worry for a while but it keeps getting reinforced every year as studies keep coming in and the failure to produce even a marginal therapy keep piling up. I have said once or twice the problem might be the model animals, not like it's my own original idea either - most dementia researchers have considered the possibility from what I've read.

That being said, any therapy based on introducing new cells into the brain will have added complexity if the human brain has completely null regenerative potential - we'd have to delve into utterly silenced signalling pathways, and who knows what could happen in an adult brain if we reactivate those. Especially a damaged one. The increased complexity doesn't make it impossible it just makes me think about the overoptimistic timescales some people put their faith in.

Posted by: Anonymoose at March 8th, 2018 5:39 PM

@Anonymoose, yeah, mice do not suffer from AD or PD so they are basically wrong models. Hovewer, times changes and now thanks to AI and other computer's approach which uses our extremely groving knowledge on one hand and various human-on-chip labs on the other hand, ten years of research and trials shrinks to months. New therapies are initially made to work a priory, animals may be used only for safety reasons, and then directly to human. I hope, Leucadia is a nice example.

"That being said, any therapy based on introducing new cells into the brain will have added complexity if the human brain has completely null regenerative potential" -- can you explain how lack of ability to produce new neurons will cause the problems with implanting new ones?

I remind you that classic SENS model is based on the worst case scenario: it doesn't use any natural regenerative ability of an organism. If we can induce them -- well! Hovewer, if not -- we will grow any number of cells manually. It is not a scientific problem, it's an engineering problem. Any engineering problem has a solution.

Posted by: Ariel at March 8th, 2018 6:42 PM

It would be nice to hear from other brainiacs (I am looking at you Audrey), to see what we can do moving forward given this more recent news. Without preserving brain cells or rejuv them within in the brain, it becomes very discerning.

I do have hope that AI and nanotechnology can overcome and rectify this issue soon

Posted by: Robert at March 8th, 2018 8:43 PM

Well, we know we can de-differentiate cells to a progenitor form - I'd expect we wouldn't want to do that in vivo in the brain as its structure is already well established and vital to function (unless it is a heavily damaged region). The question then becomes can we introduce neural stem cells in a way that will integrate successfuly to the surrounding (undamaged) structure. I expect we can. But I dont expect Alzheimer's will be solved this way, this would be more of a therapy to regenerate regions too far gone once some other therapy has stopped the disease from progressing any fuether.

Posted by: Mark at March 9th, 2018 5:50 AM

@Mark, see Undoing Aging speaker Dr. Jean Hébert -- https://www.undoing-aging.org/news/november-28th-2017

'Since then, the interest of the Hébert lab has since shifted from studying neocortex development to using the current understanding of this process to establish paradigms for neocortex repair and rejuvenation. ​

"A no-brainer? Often overlooked by many in the aging field is the possibility of using organ, tissue, and cell replacements to reverse age-related damage - even for the brain, for which a body of evidence supports the feasibility of rejuvenation through progressive cell replacement without losing one's self-identity.", says Dr. Hébert.'

Posted by: Ariel at March 11th, 2018 6:57 PM

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