Aging & Longevity

Controlling the structure and function of colloidal gels requires a detailed understanding of how the various components govern network formation and aging. In particular, molecular additives like salts are widely used to tune interparticle interactions, yet their influence on gelation pathways in complex systems such as colloidal nanocrystal gels remains inadequately understood. Here, we investigate how noncoordinating salts modulate the evolution of gels formed using chemically linked...

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Biomarkers of ageing are defined as age-related changes in body function or composition that could serve as a measure of 'biological' age and predict the onset of age-related diseases and/or residual life expectancy. We conducted the MARK-AGE Study, a European population study (3300 subjects aged 35-74) to identify a powerful set of biomarkers of ageing. A total of 362 clinical-chemistry, genetic, cellular or molecular biomarkers were analysed for each subject. Using statistical models as well...

Aging is a major risk factor for heart failure, yet the molecular mechanisms linking cardiac aging to the inflammatory pathophysiology of heart failure remain elusive. Mitochondrial dysfunction and defective organelle quality control are emerging hallmarks of the aging heart, but their biochemical underpinnings are poorly defined. Using comprehensive glycomics, we found that cardiac mitochondria from physiologically aged mice (≥ 20 months) are the major intracellular reservoirs of advanced...

How the nucleolus recovers from acute proteostatic stress, particularly in multinucleate syncytia, remains poorly understood. In the highly polarized hyphae of the model filamentous fungus Magnaporthe oryzae, we uncover a novel stress-induced spatial quality control pathway that promotes the inheritance of rejuvenated nucleolar material during nuclear division. This pathway discriminates between newly formed and damaged nucleolar compartments, selectively partitioning and sequestering the...

The redox theory of aging proposes that an oxidative imbalance, possibly amplified by infection, drives senescence. We experimentally evolved mosquitoes under early or late reproduction with or without parasite exposure, and quantified longevity, fecundity, and redox markers. Although selection generated the expected life-history divergence, there was only a poor, non-linear association between a redox gradient and longevity. Thus, oxidative stress contributed to, but did not determine, the...

Vascular dysfunction, including endothelial cell (EC) senescence and hypertension, is a hallmark of metabolic syndrome, yet its underlying mechanisms remain unclear. Here, we show that metabolic stress upregulates regulated in development and DNA damage response 1 (REDD1), driving vascular dysfunction. Overexpression of REDD1, but not the REDD1^(KK219/220AA) mutant, which cannot activate atypical NF-κB, promotes EC senescence and hypertension through NF-κB-dependent induction of miR-155-5p and...

Senescent cells (SnCs) are increasingly recognized as key contributors to osteoarthritis, with conventional strategies centered on their elimination. However, senolytic approaches face mounting limitations, driving the need for refined interventions. Here, we exploit SnCs' lipid metabolic signature to develop a senotherapeutic strategy. Given the universal lipid accumulation in SnCs and the dual role of lipids as both metabolic liabilities and essential lubricants, we engineer an injectable...

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Normal aging leads to regional vascular and neural alterations. Age-related impairments in neurovascular coupling (NVC) affect the blood-oxygen-level-dependent (BOLD) hemodynamic response function (HRF) measured with functional magnetic resonance imaging, causing changes in both amplitude and temporal dynamics. Previously, global, systematic age-related changes in HRF characteristics were demonstrated, consistent with known microvascular aging effects. In this follow-up study, a standard space...

In this meet-the-author Q&A, Scientific Editor Sara Rohban and Editor-in-Chief Laura Zahn speak with Junyue Cao about his Cell Genomics paper. He discusses his ambitions to study aging and how his newly developed method, EnrichSci, was used to look at changes over time in oligodendrocytes in the brain.

Aging is associated with oxidative stress, but specific druggable pathways remain elusive. Here, we define a conserved iron-lipid axis driving primate aging, termed "ferro-aging." Multi-tissue profiling in humans and non-human primates reveals age-progressive iron accumulation, fueling chronic lipid peroxidation orchestrated by acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4). Distinct from acute ferroptosis, this ACSL4-mediated process promotes cellular senescence and...

Aging is a major risk factor for neurodegenerative diseases, yet the underlying epigenetic mechanisms remain unclear. Here, we generated a comprehensive single-nucleus cell atlas of brain aging across multiple brain regions, comprising 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei. Integration with companion transcriptomic and chromatin accessibility data yielded a cross-modality taxonomy of 36 major cell types. We observed that transposable element (TE)...

Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS), causing psychomotor regression and metabolic crises. To accelerate drug discovery for LS, we screen a library of 5,632 repurposable compounds in neural cells from LS-patient-derived induced pluripotent stem cells (iPSCs). We identify phosphodiesterase type 5 (PDE5) inhibitors as leads and prioritize sildenafil for its clinical...

CONCLUSIONS: The effects of PM(2.5) exposure on the skeletal muscle system are age-specific, with distinct damaging effects during growth and aging, whereas skeletal muscles in middle-aged mice are resistant to PM(2.5)-induced damage.

The ageing global population faces a rising prevalence of chronic kidney disease (CKD), now recognized as a state of accelerated ageing driven by chronic low-grade inflammation-inflammaging. This review synthesizes current evidence positioning the kidney not merely as a passive target but as an active participant in systemic inflammaging, a process fueled by immunosenescence, metabolic reprogramming, and cellular senescence. We explore how resident renal cells, including tubular epithelial...

Aging alters prefrontal recruitment, often showing posterior-anterior shifts that may reflect compensatory mechanisms. Working memory capacity (WMC) is a key individual difference shaping attention and control but its role in age-related functional reorganization remains unclear. We examined 72 adults (36 younger, 36 older) who completed standardized span tasks and an fMRI visual discrimination paradigm with three manipulations: perceptual load, fine discrimination, and mapping-switch....

Balance training in geriatric rehabilitation reduces fall risk by eliciting multifaceted cortical reorganization through repeated sensorimotor challenges, supporting more efficient postural control in aging. This study combined minimum spanning tree (MST) and k-iteration second-best MST analyses to characterize training-induced changes in cortical network efficiency and resilience. Twenty-four older adults (70.4 ± 3.3 years) completed 12 sessions of stabilometer training with real-time visual...