Author Correction: Age-related decline in nuclear envelope LINC complex drives neuronal aging via axon initial segment dysfunction.
[Figure: see text]
Published Erratum↗
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Results for “neuronal aging”
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Lipofuscin in neuronal aging and diseases.
The increasing intraneuronal accumulation of lipofuscin has been linked to the aging process by a striking linear correlation between the degree of accumulation and chronological age. It has been established that age pigments are soluble in polar and nonpolar solvents; the pigment is autofluorescent and stains with PAS, Sudan black B, Nile blue osmic acid and ferric ferricyanide techniques. Whether all pigments exhibiting these properties are identical, or at least closely related, regardless of the surrounding tissue, animal species and age of the individual, is debatable. Pigment formation has been demonstrated in young and aged animals as well as in individual subjected to experimental stress and to dietetic and environmental interference. Electron microscopic studies in animals have shown a considerable variability in the fine structure of individual lipofuscin granules but the presence of "lucent vacuoles" surrounded by a unit membrane is one of the characteristic features of neuronal lipofuscin in the aged. Recently, electron microscopy, utilizing the freeze-etching technique, has provided convincing evidence which disproves the earlier view that lucent vacuoles are the remnant of lipid material dissolved and removed during the preparation of the tissues for microscopic examination. These vacuoles have also been demonstrated in freshly frozen material not previously fixed or immersed. Vacuolated pigment granules occur earlier in the area postrema than in other regions of the rat brain (Hasan and Heyder 1974). Regional differences in the time sequence of pigment deposition are present.
Aging↗
Effects of dihydroergotoxine mesylate on aging neurons in vitro.
C1300 mouse neuroblastoma cells gradually accumulate lipofuscin-like pigment when they are maintained in culture. Pigment was demonstrated by positive straining for acid phosphatase and with periodic acid-Schiff stain. Pigment was formation in cells was reduced by exposure of the cells to lower doses of dihydroergotoxine mesylate which also induced neurite formation and increased protein synthesis. Since lipofuscin appears to originate as a result of wear and tear within the cells, the drug probably exerts its beneficial effects by reducing the rate of intracellular wear and tear associated with aging.
Animals↗
Correlation of extracellular vesicle Alu RNA with brain aging and neuronal injury: a potential biomarker for brain aging.
BACKGROUND: Extracellular vesicles (EVs) are promising biomarkers for neurodegeneration. Alu elements are retrotransposons increasingly expressed with age and may be involved in aging-related diseases. OBJECTIVE: To determine the potential of Alu RNA in plasma-derived EVs as a biomarker for brain aging and neuronal injury. METHODS: EVs were isolated from plasma samples across different age groups. EV Alu RNA levels were measured and their associations with biomarkers of brain aging, including plasma neurofilament light chain (NfL), plasma amyloid-beta (Aβ42 and Aβ40), and plasma phosphorylated tau (p-Tau181), were analyzed. RESULTS: EV Alu RNA levels were increased significantly with age and were strongly correlated with plasma NfL, suggesting a strong association between EV Alu RNA and neuronal injury. Significant correlations were also found between EV Alu RNA and plasma amyloid-beta levels, while no significant association was observed with tau pathology. CONCLUSIONS: EV Alu RNA levels are elevated with age and associated with neuronal injury, highlighting their potential as a novel, non-invasive biomarker for brain aging and neurodegeneration.
Humans↗
Mapping cell-type- and age-dependent neuronal vulnerability through genome-wide in vivo CRISPRi screens in the mouse brain.
Current brain atlases are largely descriptive, cataloging correlative molecular snapshots such as gene expression signatures yet offering limited functional insight. Here, we develop a scalable, cell-type-resolved in vivo CRISPR interference (CRISPRi) platform enabling systematic gene function profiling in the mouse brain. Through genome-wide screens across four neuronal populations at three time points spanning youth to aging, we identify neuronal essential genes missed in vitro and define a consensus set of 269 neuronal core essential genes. The data reveal cell-type-specific genetic vulnerabilities, including divergent dependencies validated for exosome component 9 (Exosc9) and osteopetrosis-associated transmembrane protein 1 (Ostm1) between excitatory and inhibitory neurons. We uncover aging-specific dependencies enriched in mitochondrial and translational pathways, aligning with transcriptional changes in the aging human brain. Finally, we establish the CRISPRinvivo data portal as a community resource for in vivo screening. Altogether, this work provides a broadly applicable platform for in vivo functional genomics and a framework for building comprehensive gene-function brain atlases.
brain aging↗
Fluorescence histochemical evidence for decreased noradrenaline synthesis in sympathetic neurones of aged rats.
Measurements of formaldehyde-induced fluorescence of noradrenaline (NA) in sympathetic neuronal perikarya of aged (24-month) and younger (4-month) control rats revealed little or no NA fluorescence in many sympathetic neurones of aged rats: neuronal fluorescence in younger rats was substantially greater. Monoamine oxidase inhibition increased NA fluorescence in all rats, but the increase was greater in the 4-month controls. Reserpine administration caused an almost complete disappearance of NA fluorescence after 12 h. However, normal NA levels were restored in the 4-month controls after 48 h but not for 7 days in the aged rats.
Age Factors↗
Dispersion of cisternae of rough endoplasmic reticulum in aging CNS neurons: a strictly linear trend.
Dispersion of cisternae of rough endoplasmic reticulum (RER) in aging rats has been determined quantitatively for mitral cells of the olfactory bulb and Purkinje cells of the cerebellum using a recently published morphometric technique (Cruz Orive, '76). In both cell types dispersion of cisternae occurred throughout the period studied and in a linear fashion. The observed RER dispersion cannot be attributed to a decrease in the total amount of RER, since the total amount of RER was constant in Purkinje cells and increased in mitral cells during the age studied.
Aging↗
An in vivo and in vitro study of an aging-related neuron cytoplasmic-binding antibody in male Fischer rats.
Fischer 344 male rats showed a low average level (less than ++) of in vivo as well as in vitro neuron binding antibody at 3, 15, and 26 months. However, a significant increase with age in average intensity of binding was observed with both the in vivo and the in vitro conditions. If a criterion of ++ is used as an antibody binding level likely to have biological consequences, the percent of in vivo cases showing foci of ++ or greater intensity also rises with age from 20 to 80%; a criterion of +++ gives an in vivo rise with age of only from 10 to 20%. The in vitro incidence with the ++ criterion is already 80% at three months and rises to 90%; with the +++ criterion the incidence with age rises from 20 to 80%. No evidence was obtained to support the concept that there is a weakening of the blood-brain-barrier in 26 month rats either by the systemic injection of trypan blue or by a comparison of intensity of antibody binding between extra- and intra-barrier neurones.
Aging↗
Skin-innervating glutamatergic neurons modulate aging.
Peripheral nerves regulate skin homeostasis by secreting neurotransmitters, but their role during skin aging remains incompletely understood. Here, we report that cutaneous denervation accelerates skin aging, as evidenced by collagen reduction. Neurofilament heavy chain (Nefh) is decreased in aged skin and is predominantly expressed in vesicular glutamate transporter 2-positive (Vglut2+) skin-innervating glutamatergic neurons. Notably, dermal fibroblasts, the primary producers of collagen, frequently contact Nefh+ nerve fibers. Moreover, Nefh deletion in Vglut2+ glutamatergic neurons drives skin fibroblast senescence and collagen loss, whereas additional glutamate improves skin aging phenotypes. Mechanistically, cyclin-dependent kinase 5 (Cdk5) interacts with both Nefh and Vglut2 and maintains glutamate release and collagen homeostasis. Additionally, in skin fibroblasts, solute carrier family 1 member 3 (Slc1a3) governs the collagen-promoting and anti-senescence functions of glutamate. Together, these findings reveal Nefh-mediated glutamatergic neuromodulation of skin aging and provide therapeutic targets for aging-related skin disorders.
Animals↗
[Changes in DNA content in human brain neurons depending on age and topography].
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Age Factors↗
Structural alterations in neurons of aged canine neocortex: a Golgi study.
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Aging↗
Neuronal plasticity in primate telencephalon: anomalous projections induced by prenatal removal of frontal cortex.
When the dorsolateral prefrontal cortex in one hemisphere of a rhesus monkey is resected 6 weeks before birth and the fetus survives to postnatal ages, neurons of the corresponding cortex in the intact hemisphere issue a greatly expanded projection to the contralateral caudate nucleus in addition to a normal projection to the ipsilateral caudate. The enhancement of the crossed prefronto-caudate pathway after prenatal neurosurgery provides direct evidence for lesion-induced neuronal rearrangement in the primate telencephalon.
Animals↗
Post-mortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature.
The post-mortem brain concentrations of dopamine (DA) and homovanillic acid (HVA) were determined in 16 parts of the brain from patients with no history of neurologic or psychiatric illness. Fifteen men and nine women, with a mean age of 61.0 +/- 18.7 years (range 23--92 years) were included. They had died from either ischaemic heart disease or cancer. In the post-mortem investigation several factors were controlled: age, time between death and autopsy, time between autopsy and chemical analysis and storage time (-20 degrees C). The DA concentrations in the different brain areas were found to be positively intercorrelated, especially those in the basal ganglia, hippocampus and the mesencephalon. The HVA concentrations measured in various cortical structures were also positively intercorrelated. In several regions of the brain there was a significant inverse correlation between the DA and HVA concentrations. The DA and HVA concentrations did not differ according to sex, but age had a marked influence on the DA concentration. Significant decrease with age was observed in the nucleus caudatus, globus pallidus, mesencephalon, hippocampus and in the cortex gyrus hippocampus. These findings are discussed in relation to the effect of aging neurons. A review of human post-mortem investigations on DA and HVA concentrations is also presented.
Adult↗
Growth and myelination of goldfish optic nerve fibers after retina regeneration and nerve crush.
Axonal regeneration in the optic nerve and tectum of the goldfish was studied both after retina regeneration and nerve crush. The retina regeneration was evoked by ouabain-induced damage of at least the ganglion cells and cells of the inner nuclear layer. The necrotic retinal neurons are substituted by mitotic processes in the outer nuclear layer and the marginal growth zone at the ora serrata. The axons of these newly developed retina ganglion cells grow through the degenerating, but mechanically undamaged, optic nerve into the tectum, establishing there synaptic contacts already 16 days after the intraocular ouabain-injection. The fibers were myelinated at first in the tectum, later on in the optic nerve. Thus, the myelination process proceeds in retrograde direction. About 60--80 days after injection the myelination has become nearly normalized. On the contra-lateral side of the same animal, the optic nerve was crushed near the eye-bulb. The axons of the original retina ganglion cells grow out into the degenerating optic nerve and tectum. They also find synaptic contacts and are myelinated in retrograde direction, but to a much lesser extent than the axons of the regenerated retina ganglion cells. An axonal factor is discussed, which would influence the oligodendroglial myelination activity. The effectiveness of this factor is probably dependent on the neuronal age and suggested to be triggered by the establishment of synaptic contacts.
Animals↗
Neuronal involution during ageing. Ultrastructural study in the rat cerebellum.
Involutive phenomena have been investigated by electron microscopy in the Purkinje Pk neuron of the cerebellar cortex of the aging rat. The still limited number of specimens available to date, however, suggest an age-related progression of morphological and functional deteriorations involving particularly the intraneuronal "nucleus-ribosome system" (NRS). The impairments are characterized by changes in the nucleolar texture. These alterations are accompanied by modifications in the repartition and relative proportion of RNP components of the nucleolus. In addition, other nuclear elements such as interchromatin and perichromatin granules may vary in importance with age. Recognizable changes in the ribosomal constituents of the NRS are evidenced by modifications in the density and distribution of free ribosomes. An altered structure and organization of GER cisternae are also evident. Furthermore, "light" cytoplasmic areas, an increased evidence of neurotubules and the gradual congestion of the pericaryon by age pigments are other valuable ultrastructural features that may be regarded as part of the sequence of morphologic events occurring during neuonal ageing. The above ultrastructural data will subsequently form the basis of a model of ageing in the nerve cell, which will complete the previously proposed model of neuronal maturation. Therefore, this long-term study essentially purports the investigation of subcellular events taking place in the Pk neuron all along the normal life span in rats. This model will also be used to evaluate the changes in the sequence and the reinforcement of the processes of evolution versus involution as affected by certain xenobiotics, such as abused drugs(alcohol and narcotics). The intraneuronal modifications found in the nuclear and cytoplasmic structures of the NRS could possibly reflect the molecular dysfunction related to the production of various types of RNA and neuronal proteins. This hypothesis is supported by biochemical data obtained from analysis of the brain of aged animals. Ultrastructural and biochemical data appear to be in good agreement with the neurophysiologic interpretation of a slow-down and reduced efficiency of the CNS during the progressive development of senescence in human and animal subjects.
Age Factors↗
Compensatory synapse growth in aged animals after neuronal death.
The capacity of neurons to grow new synapses following partial denervation has been studied in the brain of aged rats and compared to that of younger animals. Lesion induced synapse formation is reduced in aged rats in the hippocampus and septum, two brain areas which show particularly robust growth responses in younger animals. The rate of growth as well as the final magnitude of the response is diminished in aged animals. A possible mechanism for the decreased growth response in aged animals is discussed in light of current models of reactive synaptogenesis. The loss of a compensatory growth response in the aged animal may be one of the factors which contribute to decreased brain plasticity and the slower and poorer recovery from brain damage following injury.
Aging↗
Accelerated ageing or selective neuronal loss as an important cause of dementia?
Extensive biochemical analysis of whole temporal lobe from cases of dementia and controls suggests that Alzheimer's disease is a primary degenerative nerve-cell disorder and not the result of accelerated ageing. There is selective loss of neocortical cholinergic neurones. Transmitter systems apart from the cholinergic system appears to be affected, but to a lesser extent, and there are no significant changes in the caudate nucleus. The change in cholinergic neurones has been confirmed in biopsy samples.
Aged↗
Microtubules observed within the cistern of RER in neurons of the aged dog.
Twenty-seven randomly selected dogs ranging from 1 month to 16 years of age were examined light- and electron microscopically. An intraneuronal inclusion body was found im 13 of 27 cases. In particular, 12 of 13 positive cases were elderly dogs of over 8 years of age. The inclusions showed amphophilic violet color with H.-E. stain and measured 3--42 micrometer in diameter. Histochemically, they were thought to be a glycoprotein complex. The inclusions were characterized by the electron microscopy and composed of aggregated cistern of RER closely packed with tubular structures. The individual tubules measured about 24 nm in diameter and had 11--13 subunits forming their walls. These constituents were very similar to those of microtubules. The occurrence of the inclusion bodies showed an apparent age-dependency.
Aging↗