Fight Aging!

Does the adult human brain normally produce a significant number of new neurons, integrating them into new networks? This process is called neurogenesis, and until the 1990s, the answer was thought to be no. Then studies in rodents found that animals of those species do produce new neurons at an appreciable pace, and that this was important to memory, learning, degree of recovery from damage such as stroke, as well as aging and neurodegeneration, as the pace of neurogenesis declines with age. Studies in humans followed to provide supporting evidence that looked convincing enough to believe that rodents were a good model for other mammalian species, including our own. Then, just recently, a well-conducted study in humans found no evidence of any significant level of neurogenesis in adult human brains. Given the degree to which the scientific community is enthusiastically in search of ways to enhance regeneration in the central nervous system, this has produced the expected level of debate.

For today, and as a further illustration of what a field in flux looks like, I'll point out another new study in which the researchers feel fairly confident in claiming that adult neurogenesis both occurs and proceeds at similar levels in both old and young humans. Science is never a matter of absolute confidence in any piece of knowledge; as a layperson, one has to weigh the studies and the discussions of experts, for and against. Here, however, the situation is disordered and uncertain: not enough time has passed for the research community to properly process the new discoveries. Expect that to require some years to reach a new consensus; it takes a year at minimum to complete a suitably weighty investigation, and another year to pass the peer review gauntlet and be published.

The overwhelming weight of evidence remains in favor of adult neurogenesis in rodents, while in humans the results and methodologies are in a sudden state of uncertainty. Yet a great deal of work has proceeded in recent years based on the assumed existence of adult neurogenesis, and various neurological phenomena shared by humans and rodents have been linked by theories that prominently feature adult neurogenesis. So it isn't just a matter of a battle of a few cell-level studies of the brain, but rather of the validity of a broad segment of scientific endeavor over the past few decades. That is not to mention the hopes of an easier road in the future towards ways to induce functional regeneration in the aging brain.

Older adults grow just as many new brain cells as young people

Researchers show for the first time that healthy older men and women can generate just as many new brain cells as younger people. There has been controversy over whether adult humans grow new neurons, and some research has previously suggested that the adult brain was hard-wired and that adults did not grow new neurons. This studycounters that notion, and the findings may suggest that many senior citizens remain more cognitively and emotionally intact than commonly believed.

"We found that older people have similar ability to make thousands of hippocampal new neurons from progenitor cells as younger people do. We also found equivalent volumes of the hippocampus (a brain structure used for emotion and cognition) across ages. Nevertheless, older individuals had less vascularization and maybe less ability of new neurons to make connections. It is possible that ongoing hippocampal neurogenesis sustains human-specific cognitive function throughout life and that declines may be linked to compromised cognitive-emotional resilience.

Human Hippocampal Neurogenesis Persists throughout Aging

Healthy aging is crucial in a growing older population. The ability to separate similar memory patterns and recover from stress may depend on adult hippocampal neurogenesis (AHN), which is reported to decline with aging in nonhuman primates and mice. New neurons are generated in the dentate gyrus (DG) of the adult human hippocampus, even after middle age, but the extent to which neurogenesis occurs in humans is highly debated and quantitative studies are scarce.

Phylogenetic differences between humans and rodents mandate assessment of the different stages of neuronal maturation in the human DG. For example, striatal neurogenesis is found only in humans, while olfactory bulb neurogenesis is absent in humans but present in other mammals. Previous analyses of human AHN did not address the effects of aging, although studies have examined AHN in older populations. Using histological techniques that could not distinguish mature and immature neurons, several groups estimated that DG neurons did not decline in aging humans.

AHN and angiogenesis are co-regulated. Exercise enhances cerebral blood volume, which results in more AHN in mice and better cognitive performance in humans, but it may have a reduced impact in older people. Thus, we quantified AHN, angiogenesis, and DG volume and their relationship in people of different ages, hypothesizing that they would concurrently decrease with aging and correlate with each other. Given the different functions of the rostral and caudal DG, we assessed the anterior, mid, and posterior hippocampus postmortem from 28 women and men 14 to 79 years of age. In each region, we characterized and quantified angiogenesis, volume, and cells at different maturational stages in the DG neurogenic niche, using unbiased stereological methods. To avoid confounders, subjects studied had no neuropsychiatric disease or treatment.

In medication-free subjects with no brain disease and no reported cognitive impairment, good global functioning as per Global Assessment Scale, and low recent (last 3 months) life event-related stress, quantified by St. Paul-Ramsey Life Experience Scale, we found persistent AHN into the eighth decade of life, and stable DG volume over a 65-year age span. In contrast, we found declining neuroplasticity and angiogenesis with older age, and a possibly diminished multipotent quiescent radial-glia-like type I neural progenitor cells (QNPs) pool selectively in anterior-mid DG, while the QNP pool remained unchanged in posterior DG, possibly reflecting less cognitive and emotional resilience with aging.

Older nonhuman primates and rodents have more granule neurons (GNs) and less AHN than younger ones, contrary to our findings in humans. Since new GNs may assist in pattern separation and old GNs in pattern completion, steady AHN and concurrent elimination of older GNs likely supports human complex learning and memory and emotion-guided behavior throughout a long lifespan. Persistent AHN is vital for preserving cognitive flexibility and allowing memory-guided decision-making without the interference of irrelevant outdated information. Our findings of thousands of new intermediate neural progenitors (INPs) and immature neurons at the time of death, in anterior, mid, and posterior human subgranular zone, suggest that the number of newly generated neurons could be sufficient for them to have a relevant impact on the DG circuit.