Cognitive Decline With Aging

Experiments with mice suggest that the aging brain accumulates astrocyte cells with an inflammatory phenotype that lose their normal function and release factors toxic to neurons.  This may also contribute to mental decline in aging humans.  These findings can eventually lead to approaches to reverse these processes.  Abstract:

The decline of cognitive function occurs with aging, but the mechanisms responsible are unknown. Astrocytes instruct the formation, maturation, and elimination of synapses, and impairment of these functions has been implicated in many diseases. These findings raise the question of whether astrocyte dysfunction could contribute to cognitive decline in aging. We used the Bac-Trap method to perform RNA sequencing of astrocytes from different brain regions across the lifespan of the mouse. We found that astrocytes have region-specific transcriptional identities that change with age in a region-dependent manner. We validated our findings using fluorescence in situ hybridization and quantitative PCR. Detailed analysis of the differentially expressed genes in aging revealed that aged astrocytes take on a reactive phenotype of neuroinflammatory A1-like reactive astrocytes. Hippocampal and striatal astrocytes up-regulated a greater number of reactive astrocyte genes compared with cortical astrocytes. Moreover, aged brains formed many more A1 reactive astrocytes in response to the neuroinflammation inducer lipopolysaccharide. We found that the aging-induced up-regulation of reactive astrocyte genes was significantly reduced in mice lacking the microglial-secreted cytokines (IL-1α, TNF, and C1q) known to induce A1 reactive astrocyte formation, indicating that microglia promote astrocyte activation in aging. Since A1 reactive astrocytes lose the ability to carry out their normal functions, produce complement components, and release a toxic factor which kills neurons and oligodendrocytes, the aging-induced up-regulation of reactive genes by astrocytes could contribute to the cognitive decline in vulnerable brain regions in normal aging and contribute to the greater vulnerability of the aged brain to injury.

No Evidence For Exercise Benefit For Depression And Cognition?

Contrary to popular conceptions, a study here and another one here did not find any positive effect of exercise (at least aerobic exercise) on depression or cognition. However, this is not the last word, and more studies are necessary.  Even if these two studies are correct, exercise has enormous health benefits for physical fitness and overall physical and psychological well-being.

Cosmic Rays And Cognitive Decline (And A Hypothesis)

By NASA/JPL-Caltech/SwRI - http://photojournal.jpl.nasa.gov/jpeg/PIA16938.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=26429266

Galactic cosmic radiation may prove  a problem for deep-space travel, and a study demonstrates that similar high-intensity radiation in mice caused cognitive decline and changes in gene expression in the hippocampus (a part of the brain whose importance is discussed in the abstract reproduced below).  One wonders if long exposure to the less intense, lower energy cosmic radiation that we are exposed to on the Earth's surface contributes to cognitive decline with age.  Therefore, the hypothesis is that long-term exposure to weaker cosmic radiation may have similar effects to short-term exposure to more intense cosmic radiation.  On the other hand, it may be possible there is a threshold effect and only high energy does the damage.  We may be adapted to deal with lower level radiation on the Earth's surface; however, cognitive decline with old age may not be strongly selected against if it is far enough removed from the reproductive age. In summary it is a hypothesis worth looking into.  Abstract:

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1H + 16O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1H + 16O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1H (0.5 Gy, 150 MeV/n) and 1 h later with 16O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1H + 16O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1H + 16O at three months postirradiation.