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NSF’s grant cuts fall heaviest on scientists from underrepresented groups
Projects to broaden participation were cut disproportionately—and were often led by Black scientists, women, and those with disabilities
This mass of amber traps evidence of an ancient tsunami
Deep-sea rocks suggest giant waves pounded modern-day Japan 115 million years ago
Microglial TMEM119 binds to amyloid-beta to promote its clearance in an Abeta-depositing mouse model of Alzheimer's disease
The progression of Alzheimer's disease (AD) involves temporal dynamics of microglial activation. Restoring or maintaining microglial homeostasis has emerged as a promising therapeutic strategy to combat AD. Transmembrane protein 119 (TMEM119) is a homeostatic marker of microglia but has not been fully studied under AD pathological conditions. Here, we observed that amyloid-beta (Aβ) induced a decrease in TMEM119 expression in microglia, and TMEM119 deficiency increased AD progression in the...
The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...
Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline
Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up...
Stem cells against Parkinson's
No abstract
Stem cells show promise in Parkinson disease
No abstract
Causal relationship between molecular markers of biological aging and orthopedic diseases: A two-sample bidirectional Mendelian randomization study
CONCLUSIONS: This study suggests a potential causal associations between molecular markers of biological aging and orthopedic diseases, suggesting avenues for future research into the underlying mechanisms.
Immersive virtual reality for older adults: Challenges and solutions in basic research and clinical applications
Immersive virtual reality (IVR) offers significant potential for aging research, providing a controlled yet ecologically valid platform for studying cognitive, emotional, and motor processes, as well as supporting interventions and diagnostic assessments in older adults. However, its usability can be hindered by age-related sensory, motor, and cognitive changes, which may contribute to anxiety, disorientation, and reduced task engagement. In this narrative review, we examine the challenges older...
The genetic risk factors, molecular pathways, microRNAs, and the gut microbiome in Alzheimer's disease
Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...
Single-Cell RNA-Seq Reveals Aging-Related Impairment of Microglial Efferocytosis Contributing to Apoptotic Cells Accumulation After Retinal Injury
Aging is associated with increased retinal cell apoptosis, which contributes to decreases in retinal function. Apoptotic retinal cell clearance relies on microglial efferocytosis, but the impact of aging on this process has not been fully elucidated. In this study, we aimed to shed light on this by using single-cell RNA sequencing (sc-RNA-seq) to compare young and aged mouse retinal transcriptional profiles, in which 74,412 retinal cells from young and aged mice were classified into 10...
USP14/S100A11 axis promote colorectal cancer progression by inhibiting cell senescence
The aberrant expression of S100A11 has been identified in various malignancies but its functional roles and underlying mechanisms in colorectal cancer (CRC) have not been fully elucidated. Therefore, this study was designed to investigate the expression of S100A11 and its functional significance in CRC, indicating that S100A11 is significantly upregulated and correlates with poor survival outcomes in CRC. Functionally, S100A11 knockdown in CRC cell lines inhibited cell proliferation, invasion,...
Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline
Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up...
Regulating obesity-induced osteoarthritis by targeting p53-FOXO3, osteoclast ferroptosis, and mesenchymal stem cell adipogenesis
Obesity-related osteoarthritis (OA) and the molecular mechanisms governing multiple joint structural changes that occur with obesity are not well understood. This study investigated the progression of obesity in mice and validated the results using human joint samples post-arthroplasty. The results show that obesity is associated with the degeneration of the cartilage layer and abnormal remodeling of the subchondral bone layer, and this occurs alongside aging and DNA damage in chondrocytes,...
Mammography screening and risk factor prevalence by sexual identity: A comparison of two national surveys
CONCLUSIONS: LGBQ women were more likely than straight women to be exposed to breast cancer risk factors, which were compounded by lower screening and facing health care access barriers. It is crucial to identify interventions for screening and risk reduction that are accessible and effective for LGBQ women, particularly bisexual/queer women and those aging into screen-eligibility.
hTERT Increases TRF2 to Induce Telomere Compaction and Extend Cell Replicative Lifespan
Replicative senescence occurs in response to shortened telomeres and is triggered by ATM and TP53-mediated DNA damage signaling that blocks replication. hTERT lengthens telomeres, which is thought to block damage signaling and the onset of senescence. We find that normal diploid fibroblasts expressing hTERT mutants unable to maintain telomere length do not initiate DNA damage signaling and continue to replicate, despite having telomeres shorter than senescent cells. The TRF1 and TRF2 DNA binding...
Ythdf2 Ablation Protects Aged Retina From RGC Dendrite Shrinking and Visual Decline
Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m⁶A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects....
Microglia Single-Cell RNA-Seq Enables Robust and Applicable Markers of Biological Aging
"Biological aging clocks"-composite molecular markers thought to capture an individual's biological age-have been traditionally developed through bulk-level analyses of mixed cells and tissues. However, recent evidence highlights the importance of gaining single-cell-level insights into the aging process. Microglia are key immune cells in the brain shown to adapt functionally in aging and disease. Recent studies have generated single-cell RNA-sequencing (scRNA-seq) datasets that...
UTX (KDM6A) promotes differentiation noncatalytically in somatic self-renewing epithelia
The X-linked histone demethylase, UTX (KDM6A), is a master regulator of gene enhancers, though its role in self-renewing epithelia like the skin is not well understood. Here, we find that UTX is a key regulator of skin differentiation via the regulation of retinoic acid (RA) signaling, an essential metabolic pathway in both skin homeostasis, as well as in the treatment of an array of skin conditions ranging from cancer and acne to aging. Through deletion of Utx in the skin, we demonstrate direct...
Amyloid-beta peptide toxicity in the aged brain is a one-way journey into Alzheimer's disease
Aging is the primary risk factor for Alzheimer's disease (AD), and the aging brain shares many characteristics with the early stages of AD. This study investigates the interplay between aging and amyloid-beta (Aβ) induced pathology. We developed an AD-like in vivo model, using the stereotactic injection of Aβ(1-42) oligomers into the hippocampi of aged mice. Cognitive impairments were assessed using a Y maze. Immunohistochemical and protein analyses were conducted to evaluate neuronal survival,...