A Dual Approach to Glioblastoma Treatment with Epigenetic Reprogramming and Neurogenetic Modulation.

Glioblastoma is a highly aggressive primary brain tumour marked by extensive genomic and epigenomic alterations, cellular heterogeneity, and therapeutic resistance. Despite maximal surgical resection followed by chemoradiotherapy, median survival remains approximately 15 months, reflecting the …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

CRISPR/Cas9 system-mediated p21 knockout impairs the MITF signaling pathway.

The CRISPR/Cas9 method facilitates targeted disruption of gene sequences, providing a reliable means to analyze gene-dependent regulatory pathways. This study aims to investigate melanogenesis in p21-knockout B16F1 cells generated by the CRISPR/Cas9 system. The mutation …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

NPC1 deficiency engages a lysosome - genome - immune program linked to neurodegeneration and cellular aging signatures

Lysosomal dysfunction is a prominent feature of neurodegeneration and aging, yet how primary defects in lysosomal trafficking are converted into progressive cellular decline remains poorly understood. Niemann Pick disease type C (NPC), caused by impaired …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

Mendelian Randomization Revealed Potential of mTOR Inhibitors for Treatment of Osteoporosis: Evidence From GWAS and Transcriptome Data.

AIMS: Numerous preclinical studies suggested that targeted inhibition of mammalian target of rapamycin (mTOR) may be beneficial for the treatment of osteoporosis. However, the relevance of these findings to human populations remains unclear. We hypothesized …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Ahcy Acts as an Effector of Hnf4a-Driven Super-Enhancer Activation to Alleviate MASLD During Intermittent Fasting.

Intermittent fasting (IF) ameliorates metabolic dysfunction-associated steatotic liver disease (MASLD), but the underlying mechanism remains unclear. Combined CUT&Run and transcriptomic analysis shows that hepatic Ahcy is controlled by the super‑enhancer (SE) and acts as a …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Genetic associations with longevity in a Calabrian cohort: an exploratory genome-wide study.

Human longevity is a complex trait shaped by genetic background and population-specific factors. Calabria, a region in Southern Italy with a high prevalence of centenarians and relative genetic isolation, is a valuable model for investigating …

44 Early
Design 5
Sample 7
Peer Review 16
Replication 6
Transparency 10

Two novel indigenous Levilactobacillus brevis probiotic strains MKMB04 and MKMB05 enhance longevity and protect intestinal barrier function through antioxidant and anti-inflammatory mechanisms.

Aging is characterized by progressive oxidative stress, mitochondrial dysfunction, chronic inflammation and intestinal barrier impairment, contributing to increased susceptibility to age-associated disorders. Targeting redox imbalance and epithelial dysfunction represents a promising therapeutic strategy to promote …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Conditional deletion of human STN1 leads to telomere dysfunction, genome instability and proliferation defects.

CTC1-STN1-TEN1 (CST) is a heterotrimeric, RPA-like complex that binds single-stranded DNA, stimulates DNA polymerase α-primase, and functions in several genome maintenance pathways, including telomere maintenance and DNA replication and repair. During telomere replication, CST prevents …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Multimodal Deep Learning Reveals the Modular Genetic Architecture of Cardiovascular Aging

Age is the dominant risk factor for cardiovascular disease, yet individuals of the same chronological age can differ markedly in the organs and biological pathways through which cardiovascular vulnerability emerges. We used deep learning to …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

Parallel adaptive responses to postponed reproduction increase lifespan and immune defense

Experimental evolution studies with Drosophila melanogaster have long played a role in the effort to dissect the genetic basis of aging and longevity. While selection for postponed reproduction reliably extends lifespan, additional phenotypic consequences and …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Is APOE ε2 always a protective allele? Deviations in Hardy-Weinberg equilibrium in admixed Brazilian elderly individuals

The APOE gene is a critical determinant of human healthspan and longevity, with the rare{varepsilon} 2 allele traditionally viewed as a universal protective factor against Alzheimer s disease (AD) and a driver of exceptional lifespan. …

34 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 12

Sequence-directed R-loop formation coupled with DNA methylation reprogramming during polyploidization of Brachypodium.

R-loops are three-stranded structures consisting of a DNA:RNA hybrid and a single-stranded DNA, which play essential biological roles in eukaryotes. However, their functions during hybridization and the long-term evolutionary trajectory of polyploidization remain unclear. Here, …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Intervening in aging and related diseases with gene therapy techniques.

Aging is the primary risk factor for most chronic diseases, and the global rise in aging populations presents an escalating challenge due to functional decline and multimorbidity. Gene therapy provides a versatile framework for modulating …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Centromeric footprints preserve telomere integrity in ALT cancers.

Alternative lengthening of telomeres (ALT) is a specialized telomere extension mechanism associated with 5-10% of all cancers1. Although ALT has been linked to epigenetic dysregulation and genome instability, specific genomic and epigenetic rearrangements generated after …

47 Early
Design 5
Sample 7
Peer Review 19
Replication 6
Transparency 10

Chronic psychological stress potentiates IgE class switch recombination via glucocorticoid receptor-mediated epigenetic reprogramming of B cells.

BACKGROUND: Chronic psychological stress is a well-recognized factor in the exacerbation of allergic diseases, with IgE playing a central role in their pathophysiology. However, the exact molecular mechanisms by which stress hormones directly influence IgE …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Dynamics of gut bacteriophage in diversity outbred mice studied over lifespan and during extreme caloric restriction.

BACKGROUND: The majority of bacteria in the vertebrate gut harbor integrated bacterial viruses ("bacteriophages" or "phages"; integrated phage are termed "prophages"). To probe phage replication strategies in the mammalian gut microbiome, we investigated phage activity …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10

Multi-Omics Integrative Analysis of the Aspirin-Gut-Brain-Glioma Axis: Transcriptomic, Proteomic, Epigenetic, Mendelian Randomization, and Single-Cell Transcriptomic Evidence Converges on NEO1/Hepcidin Iron Reprogramming and Ferroptosis Vulnerability

Background: Despite epidemiological interest in aspirin's chemopreventive potential against glioma, the underlying multilayered molecular mechanisms spanning gut microbial ecology, COX-2/PGE2 signaling, inter-organ iron homeostasis via the NEO1/hepcidin regulatory axis, epigenetic reprogramming, and ferroptosis have not …

39 Early
Design 5
Sample 7
Peer Review 4
Replication 6
Transparency 17

Electrical stimulation promotes longevity and regeneration in a colonial chordate.

Endogenous bioelectric currents regulate development and regeneration, but their influence on organismal longevity and stem cell-mediated repair is not well understood. We demonstrate that a brief, clinically safe pulse of electrical current (PEC) produces lasting …

46 Early
Design 5
Sample 7
Peer Review 18
Replication 6
Transparency 10

Genetic secrets of extreme old age discovered in Taiwan

Genes linked to reaching 95 were found, but your heart health and blood pressure matter far more for long life.

Researchers identified six genetic variants linked to living past 85, 90, and 95 years in a Taiwanese population. When combined with health information, these genetic clues modestly improved predictions of extreme longevity, especially for those …

53 Promising
Design 8
Sample 10
Peer Review 15
Replication 11
Transparency 9

Caloric restriction reprograms skeletal muscle molecular pathways in non-human primates: potential relevance to human aging biology.

BACKGROUND: Caloric restriction (CR), achieved by reducing energy intake without malnutrition, has been shown to preserve muscle function and delay age-related declines in strength and mobility by modulating key metabolic and molecular pathways involved in …

38 Early
Design 5
Sample 7
Peer Review 10
Replication 6
Transparency 10