Aging & Longevity

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...

Klotho (Kl) is an anti-aging protein primarily produced in the kidney and the choroid plexus (CP, where it regulates cerebrospinal fluid composition and exerts neuroprotective effects. Here, we investigated the age-dependent consequences of a CP-specific Kl deletion on CP structure and function using mice lacking Kl exclusively in CP epithelial cells (Kl^(ΔCP)). In control mice, aging markedly disrupted CP architecture and cilia organization both in the lateral (LV-CP) and fourth ventricle...

Hollow stems have independently evolved multiple times across the plant kingdom and play crucial roles in plant development and various environmental adaptations. However, the mechanisms underlying stem hollowness remain poorly understood. Water spinach (Ipomoea aquatica) is one of the few hollow-stemmed plants in the Convolvulaceae family (eudicot: asterid), and its hollow stems are essential for thriving in aquatic environments. Using histochemical staining and transcriptome analysis, we found...

Oncogenic Ras is known to induce DNA replication stress, leading to cellular senescence or death. In contrast, we found that it can also trigger polyploid Drosophila ovarian nurse cells to die by inducing aberrant division stress. To explore intrinsic protective mechanisms against this specific form of cellular stress, here, we conducted a genome-wide genetic screen and identified the E2 enzyme Uev1A as a key protector. Reducing its expression levels exacerbates the nurse cell death induced by...

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The tumor suppressor p53 orchestrates critical cellular responses to stress, including cell cycle arrest, DNA repair, senescence, and apoptosis. While extensive research has elucidated many aspects of p53 function, the isoform-specific mechanisms governing cell fate decisions remain incompletely understood. Here, we leverage the simplified p53 gene architecture in Drosophila to systematically dissect the apoptotic and tumorigenic potential of individual p53 isoforms, uncovering fundamental...