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One faulty gene copy can make the heart’s DNA fold the wrong way

2 weeks 1 day ago
Researchers have discovered that a gene linked to congenital heart disease acts like an architect for the heart cell’s DNA. Losing just one copy of TBX5 can cause the genome’s carefully folded 3D structure to unravel, disrupting the genes needed to build a healthy heart. The effects can vary from cell to cell, which may help explain why people with the same mutation develop different heart defects. The same hidden mechanism could also play a role in other birth defects.

Drinking orange juice every day may change thousands of genes

2 weeks 1 day ago
Orange juice may have a much bigger effect on the body than scientists once realized. Drinking it regularly appears to influence genes tied to inflammation, blood pressure, metabolism, and blood sugar control, while studies have also found improvements in cholesterol and blood vessel health. Researchers suspect natural citrus compounds such as hesperidin may be partly responsible. Even the gut microbiome may benefit.

How to build an AI-driven digital organism

2 weeks 1 day ago
Biology lies at the core of medicine, pharmacy, public health and longevity. However, in the physical world, biology is often too complex to manipulate and too expensive and risky to tamper with. In this Perspective, we put forward a vision of using AI to model and simulate biology and life. We present our vision on how to address this challenge through the construction of an AI-driven digital organism (AIDO)-a system of integrated multiscale foundation models-in a modular, connectable and...
Le Song

Peroxynitrite: A potential therapeutic target for Alzheimer's disease

2 weeks 1 day ago
The pathogenesis of Alzheimer's disease (AD) involves multiple pathological processes, including β-amyloid (Aβ) deposition, aberrant tau modification, oxidative stress, and neuroinflammation. The molecular interaction mechanism among them remains to be further clarified. Peroxynitrite (ONOO⁻) is a potent oxidizing and nitrating reactive nitrogen species formed from the rapid reaction between nitric oxide and superoxide. It mediates protein nitration, lipid peroxidation, and mitochondrial damage,...
Wei-Zhen Liu

The role of cognitive function in age-related changes in spatiotemporal gait: Findings from a community-based cross-sectional study

2 weeks 1 day ago
CONCLUSION: Temporal gait components were associated with age primarily through cognition-related pathways and may serve as candidate digital markers of cognitive impairment, although longitudinal validation is required. Interpretation is limited by the cross-sectional design and the restricted representation of individuals with moderate-to-severe dementia.
Ran An

Mitochondrial dysfunction as a key mediator of endplate chondrocyte senescence: emerging insights and targeted interventions

2 weeks 1 day ago
Intervertebral disc degeneration (IVDD) is a leading global cause of chronic pain and functional impairment. The senescence of endplate chondrocytes (EPCs) associated with the IVDD cascade, with mitochondrial homeostatic imbalance serving as the central pathological key mediator. EPCs inhabit a physiological niche defined by hypoxia, limited nutrients, and high mechanical loads, requiring precise metabolic regulation and mitochondrial quality control. This review integrates recent advances in...
Ruohui Tang

Thymus regeneration in countering immunosenescence: Mechanisms, strategies and future perspectives

2 weeks 1 day ago
Immunosenescence refers to the progressive decline in immune system functionality associated with aging, with thymic involution identified as a primary driver of this process. The thymus, the central organ for T cell development, begins to atrophy from puberty onward, resulting in a marked reduction in naive T cell output and a significant decrease in the diversity of T cell receptor (TCR) repertoires. This decline compromises the immune system's capacity to mount effective responses against...
Feiyang Hua

Conformational drift of long-lived proteins in the human eye: Insights into post-translational modifications and analytical techniques for ocular protein ageing

2 weeks 1 day ago
Long-lived proteins provide a uniquely informative substrate for studying the molecular chemistry of human ageing, and the eye offers one of the most accessible and spatially resolved systems for examining this process. The lens remains the principal model: its central crystallins are synthesized during embryonic and early postnatal life and are retained throughout the lifespan, thereby preserving a cumulative record of irreversible chemical damage. We then extend this framework to other ocular...
Damiano Calcagno

Magic or realism?

2 weeks 1 day ago
Recently discovered genetic variants seem to protect against Alzheimer's disease, suggesting a path toward a cure. But are their powers believable?
Charles Piller

Socioeconomic inequalities in functional ageing trajectories in England and Canada: A comparative longitudinal cohort study

2 weeks 1 day ago
CONCLUSIONS: Socioeconomic inequalities in functional ageing are apparent in England and Canada, are larger in England than in Canada, and are not fully explained by common risk factors. These findings suggest that multilevel approaches, combining individual-level interventions with structural measures, are required to address socioeconomic inequalities and cross-country differences in functional ageing. Variation in wealth associations by sex suggests that approaches to reducing socioeconomic...
Stephanie Schrempft

Parkinson's disease-associated PINK1 loss disrupts ensheathing glia and causes dopaminergic neuron synapse loss

2 weeks 1 day ago
Parkinson's disease (PD) is commonly associated with the loss of dopaminergic neurons in the substantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear. PINK1 is mutated in familial PD, and through unbiased single-cell sequencing of the entire brain of Drosophila Pink1 models, we observed significant gene deregulation in ensheathing glia (EG), cells that...
Lorenzo Ghezzi

Nonlinear association between age and verbal fluency and moderation by adiposity: cross-sectional evidence from the Look Up 8+ study

2 weeks 1 day ago
CONCLUSION: Age and VF are nonlinearly associated across adulthood, with educational attainment being a major determinant. Higher central adiposity is associated with lower VF and moderates the associated with age. Lower-limb functional performance was independently associated with VF, potentially reflecting a functional pathway linking adiposity, mobility, and cognitive aging.
Giulia Giordano

Ovarian Extracellular Matrix Mechanics Regulate Oocyte-Follicle Interactions During Female Reproductive Aging

2 weeks 1 day ago
Female reproductive aging is associated with ovarian functional decline, leading to infertility. During aging, biochemical and biophysical changes in the ovarian extracellular matrix (ECM) occur, yet how these properties affect follicle growth and oocyte quality remains poorly understood. Here we describe spatiotemporal changes in the ovarian ECM with age using mass spectrometry, immunohistochemistry, and nanoindentation. While follicle stiffness remains unchanged, stromal matrix remodeling is...
Xingyu Shen

Luteolin and glycitein from Codonopsis pilosula ameliorate age-related locomotor decline in C. elegans via DAF-16-dependent but autophagy-divergent pathways

2 weeks 1 day ago
As global population aging accelerates, maintaining locomotor function in later life has become a critical biomedical challenge. This study investigates the effects of three bioactive compounds-Luteolin (Lut), Glycitein (Gly), and α-Spinasterol (α-Spin)-isolated from the traditional Chinese medicinal herb Codonopsis pilosula (Dangshen), on age-related locomotor decline using the Caenorhabditis elegans (C.elegans) model. We demonstrate that Lut and Gly significantly ameliorate the deterioration...
Yan Zhuang

Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease

2 weeks 1 day ago
Microglia, the brain's resident immune cells, are transcriptionally diverse and highly dynamic, but during aging and disease they lose their transcriptomic flexibility and adopt a chronically activated state that is associated with neuroinflammation and pathology. An emerging transcriptomic process that is also increasingly implicated in brain aging, neuroinflammation, and disease is the dysregulation of transposable elements (TEs), repetitive genomic sequences with the potential to cause...
Randy A Grant

Protective role of hemokinin-1 against age-dependent spatial memory and attention decline in mice

2 weeks 1 day ago
Age-related cognitive decline is a major social and medical challenge, but its mechanisms remain poorly understood; prevention and therapy are unsatisfactory. The tachykinin hemokinin-1 (HK-1), encoded by the Tac4 gene, is expressed in brain regions involved in learning and memory and has been implicated in neuroimmune regulation, but its contribution to age-dependent cognitive impairment remains unclear. Here, we investigated whether endogenous HK-1 modulates cognitive performance during aging....
Brigitta Tekla Tajti