Aging & Longevity

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The integration of environmental cues into cellular programs is crucial for cell function. Yet, how this integration is modulated due to cellular aging remains unclear. We propose that the 3D chromatin organization filters these signals and investigated how age-related chromatin changes in human dermal fibroblasts affect responses to mechanical tension and TGF-β. Young fibroblasts exhibited synergistic gene expression enhancement in response to combined stimuli, a response that was markedly...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, and maternal immune activation (MIA) is highly implicated in neuropathology and ASD-like phenotypes in offspring. However, the underlying regulatory mechanisms of ASD are multifactorial and remain largely unknown in MIA offspring. Here, we performed spatial transcriptome and single-nucleus RNA sequencing (snRNA-seq) analysis in MIA offspring brain to explore the neurobiological features of ASD. We obtained MIA-induced genes and...

Cell cycle progression presents a fundamental challenge to epigenome integrity, particularly due to the need to reestablish post-translational histone modifications (PTMs) following DNA replication. Although proliferative and differentiating tissues exhibit markedly different cell cycle dynamics, how these differences shape the histone modification landscape in vivo remains largely unexplored. Here, we show that levels of H3K27ac, H3K27me3, and H3K9me3 are tightly linked to cell cycle dynamics...

Tissues harbor memories of inflammation, which heighten sensitivity to diverse future assaults. Whether and how these adaptations are sustained through time and cell division remain poorly understood. We show that in mice, epidermal stem cells store lifelong, functional epigenetic records of psoriasis-like skin flares. Applying deep learning to investigate these chromatin dynamics, we unearth CpG dinucleotide density as a major driver of memory persistence. Although unnecessary for...

Aging is characterized by a decline in essential sensory functions, including olfaction, which is crucial for environmental interaction and survival. This decline is often paralleled by the cellular accumulation of dysfunctional mitochondria, particularly detrimental in post-mitotic cells such as neurons. Mitochondrial stress triggers the mitochondrial unfolded protein response (UPR^(MT)), a pathway that activates mitochondrial chaperones and antioxidant enzymes. Critical to the efficacy of the...

Mitochondrial dysfunction-driven senescence is a central mechanism in the development of osteoarthritis (OA). Leucine-rich repeat kinase 2 (LRRK2), a multifunctional kinase implicated in maintaining mitochondrial homeostasis, has been examined in several inflammatory conditions. However, its role in regulating cellular senescence and its pathogenic contribution to OA remain insufficiently understood. To clarify the mechanism by which LRRK2 contributes to OA, RNA-seq and bioinformatics analysis...

Adequate protein intake is increasingly recognized as a key determinant of healthy aging, yet its independent and diet-dependent effects on functional decline and mortality remain uncertain. Using data from 532 adults aged ≥65 years in the English Longitudinal Study of Ageing, we examined cross-sectional and longitudinal associations between multiple protein-related parameters and clinical outcomes over six years. We also evaluated whether protein intake modified or mediated the effects of two...

The search for biological mechanisms of human aging is stalled by a lack of suitable models, and it remains unknown whether and to what degree rejuvenation reported in rodents translates to people. Here we report a human induced pluripotent stem cell-derived microphysiological system modelling the white adipose tissue-liver axis in the presence of heterochronic human serum to study aging and rejuvenation in humans. We reveal changes in functional and molecular hallmarks of aging and...

Large-scale gradients of functional connectivity between brain areas organize the human neocortex, linking brain topography to the texture of cognition^(1,2). In adults, three dominant axes-sensory-association, visual-somatosensory and modulation-representation-run, respectively, from primary sensory to transmodal association areas, from visual to body-centred systems and from control and attention networks to default mode and sensory areas^(1-4). These gradients provide a compact description of...

Senescent microglia undergo significant molecular and biochemical changes associated with impaired phagocytosis of amyloid-β (Aβ), a process implicated in neurodegenerative disease progression. However, quantitative biophysical metrics capable of capturing this functional impairment-and thus elucidating the role of microglial dysfunction in disease progression-remain limited. In this study, we identify cellular dry mass, measured by label-free holotomography, in combination with cell and nuclear...

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Brain aging consists of a progressive loss of functional capacities, which is associated with a progressive cognitive decline and can lead to neurodegenerative diseases. Studies comparing the underlying molecular mechanisms of the human hippocampus between young and older adults remain scarce. In our study, we completed a transcriptomic analysis from hippocampal samples of different ages and performed 2 complementary analyses. A comparison between young and old groups revealed a set of genes...

With the number of Parkinson's patients expected to rise due to an aging population, there is an increasing need to identify new diagnostic markers. These markers should be affordable and suitable for routine use to monitor the population, help stratify patients for treatment pathways, and provide new avenues for therapy. Genetic predisposition and familial forms account for approximately 10% of Parkinson's disease (PD) cases, leaving a large fraction of the population with minimal effective...

CONCLUSION: Greater sensorymotor impairment predicts accelerated decline in naturalistic driving among cognitively normal older adults, independent of cognition. A composite SMI may provide a feasible, low-cost approach to identify older drivers at risk for declining mobility and support timely interventions to prolong safe driving.

CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.

CONCLUSION: Integrating metabolic biomarkers with standard clinical characteristics significantly improves model calibration and clinical net benefit for predicting 10-year mortality in older adults with heart failure. This approach highlights underlying mechanisms, such as mitochondrial energy dysfunction and chronic systemic inflammation, providing a practical tool for personalized care planning and targeted interventions.

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Polysaccharides are natural macromolecules with diverse bioactivities and potential health benefits. It exhibits a broad spectrum of biological effects, with extensive research supporting their antioxidative, anti-inflammatory, immunomodulatory, and anti-aging properties. The study evaluated the aging-modulatory effects of Labisia pumila polysaccharides (LPP) using Caenorhabditis elegans (C. elegans) and Drosophila melanogaster (D. melanogaster) as model organisms. LPP treatment increased the...