Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis. Mimicking an aged condition in young adults by abrogating Tet2 expression within the hippocampal neurogenic niche, or adult neural stem cells, decreased neurogenesis and impaired learning and memory. In a heterochronic parabiosis rejuvenation model, hippocampal Tet2 expression was restored. Overexpressing Tet2 in the hippocampal neurogenic niche of mature adults increased 5hmC associated with neurogenic processes, offset the precipitous age-related decline in neurogenesis, and enhanced learning and memory. Our data identify Tet2 as a key molecular mediator of neurogenic rejuvenation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870899 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.02.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.
Invest Ophthalmol Vis Sci
January 2025
Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Purpose: In the aging retina, persistent activation of microglia is known to play a key role in retinal degenerative diseases like age-related macular degeneration (AMD). Furthermore, dysregulation of the alternative complement pathway is generally accepted as the main driver for AMD disease progression and microglia are important producers of local complement and are equipped with complement receptors themselves. Here, we investigate the involvement of anaphylatoxin signaling, predominantly on Iba1+ cell activity, in light-induced retinal degeneration as a model for dry AMD, using anaphylatoxin receptor knockout (KO) mice.
View Article and Find Full Text PDFCALB1 and RPL23 Are Essential for Maintaining Oocyte Quality and Function During Aging.
Aging Cell
January 2025
State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
With advancing age, significant changes occur in the female reproductive system, the most notable of which is the decline in oocyte quality, a key factor affecting female fertility. However, the mechanisms underlying oocyte aging remain poorly understood. In this study, we obtained oocytes from aged and young female mice and performed single-cell transcriptome sequencing, comparing our findings with existing proteomic analyses.
View Article and Find Full Text PDFAn autocrine synergistic desmin-SPARC network promotes cardiomyogenesis in cardiac stem cells.
Cells Dev
December 2024
Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria; Medical University of Vienna, Center for Medical Biochemistry, Department of Molecular Biology, Vienna, Austria. Electronic address:
The mammalian heart contains cardiac stem cells throughout life, but it has not been possible to harness or stimulate these cells to repair damaged myocardium in vivo. Assuming physiological relevance of these cells, which have evolved and have been maintained throughout mammalian evolution, we hypothesize that cardiac stem cells may contribute to cardiomyogenesis in an unorthodox manner. Since the intermediate filament protein desmin and the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) promote cardiomyogenic differentiation during embryogenesis in a cell-autonomous and paracrine manner, respectively, we focus on their genes and employ mouse embryonic and cardiac stem cell lines as in vitro models to ask whether desmin and SPARC cooperatively influence cardiomyogenesis in cardiac stem and progenitor cells.
View Article and Find Full Text PDFSupplementation of essential amino acids suppresses age-associated sleep loss and sleep fragmentation but not loss of rhythm strength under yeast-restricted malnutrition in Drosophila.
J Biochem
December 2024
Department of Neurogenetics, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Sleep quality and quantity decrease with age, and sleep disturbance increases the risk of many age-associated diseases. There is a significant relationship between nutritional status and sleep outcomes, with malnutrition inducing poor sleep quality in older adults. However, it remains elusive whether, and if so how, nutritional supplementation prevents age-associated sleep problems.
View Article and Find Full Text PDFRejuvenating aged osteoprogenitors for bone repair.
Elife
December 2024
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!