Aging & Longevity

Cellular calcium (Ca^(2+))-regulating systems are compromised during aging-related disorders. Here, we show that disruption of Ca^(2+) homeostasis leads to the cytoplasmic accumulation of Ca^(2+) binding protein S100A6, which promotes Hutchinson-Gilford progeria syndrome (HGPS) and natural aging. S100A6 recruits CacyBP to facilitate the ubiquitination and degradation of PARP1, leading to DNA damage and the formation of cytoplasmic chromatin fragments (CCF), activing cGAS-STING-NF-κB pathway and...

Parkinson's disease (PD) is a neurodegenerative disease affecting the central nervous system with effects on the skeletal muscle that entails detailed characterization. Several PD-associated motor symptoms, such as rigidity, movement delays and postural instability, involve the skeletal muscle. We used the human α-syn A53T mutant mouse model to characterize the PD-associated skeletal muscle abnormalities. These mice exhibit reduced muscle weight, myofiber size and grip strength at PD onset. Gain...

This study aims to investigate the mechanism by which extract of Dendrobium officinale leaves (EDL) extends the lifespan of Caenorhabditis elegans. Untargeted metabolomics and network pharmacology analyses revealed that EDL primarily contains active components such as fatty acids, flavonoids, and polyphenols, which are predicted to potentially modulate pathways including MAPK, AMPK, mTOR, and longevity-related signaling pathways. Experimental results showed that 2 mg/mL EDL significantly...

The ageing population and the increasing prevalence of age-related diseases underscore the urgent need for targeted therapeutic strategies. Accumulating evidence indicates that quinolinic acid (QA), a neuroinflammatory neurotoxin, contributes to the pathogenesis of neurodegenerative disorders. In this study, using Caenorhabditis elegans as a model organism, we demonstrate that chronic QA exposure acts as a robust driver of accelerated aging, significantly reducing overall healthspan. This...

Higher cardiorespiratory fitness (CRF) has been linked to healthier brain ageing, which includes preservation of white matter (WM) tracts. However, whether CRF might help preserve whole-brain WM networks and whether this varies with age remains unclear. To address this gap, we used cross-sectional data from The Maastricht Study (N = 4432, mean age 59.2 ± 8.7 years, range 40-79, 51% female). We derived CRF estimates from submaximal ergometry (VO(2)-max) and WM network metrics (whole-brain node...

The properties of functional brain networks are an important determinant of cognitive function in aging and dementia. Despite this, few studies have comprehensively examined demographic and biopsychosocial predictors of functional brain networks, and none have attempted to do so across the adult lifespan while accounting for collinearity among these predictors. The current study used data from 525 individuals between the ages of 35 and 100 years from the Human Connectome Project 2.0 Lifespan...

Andes virus (ANDV) is the most virulent New World orthohantavirus, responsible for hantavirus cardiopulmonary syndrome (HCPS)-a severe and frequently fatal disease characterized by non-cardiogenic pulmonary edema, vascular collapse, and dysregulated immune activation. The April 2026 outbreak of ANDV aboard the cruise ship MV Hondius, in which several older adults were among those most severely affected, has renewed attention to host age as a potential determinant of disease severity. Although...

CONCLUSIONS: Our findings suggest that MetS may play a significant role in the development and progression of frailty. Accordingly, targeting MetS could be a viable approach for preventing or delaying the onset of frailty in older adults.

In Indonesia, adults living in rural areas have a longer life expectancy than their urban counterparts. Beyond observed longevity, attention has focused on lifespan and healthspan expectations as predictors of health outcomes. This study examines expected lifespan and expected healthspan and their associated factors among rural and urban populations in Java, Indonesia. The cross-sectional Healthy Longevity (HELO) survey collected data from the general population using in-person interviews and an...

CONCLUSIONS: Perceived control over falling among older adults with CaF is a dynamic, multidimensional process that extends beyond physical risk factors. Fall-prevention interventions should therefore move beyond purely physical components to incorporate psychological, social, and life-course dimensions, supporting adaptive appraisals, resilience, independence, and sustained engagement in daily life.

Heterointerface degradation under operational stress represents a critical limitation to perovskite solar cell longevity. Here, we demonstrate contrasting aging behaviors between bulky anionic and cationic passivators at heterointerfaces, wherein anionic species induce lattice expansion under thermal stress. To address the thermal instability of conventional passivators, we synthesized cesium pyridine-3-carboxylate, which triggers reactive surface reconstruction, suppresses ion migration, and...

Do viral infections accelerate aging, and does this acceleration scale with pathogenicity? Using transcriptomic aging clocks, we measured biological age in Drosophila melanogaster infected with four enteric RNA viruses spanning a broad pathogenicity range (i.e., reduction of host lifespan). All pathogenic infections accelerated aging and the magnitude of acceleration tracked pathogenicity. This pattern held across oral and systemic infection routes and was conserved in Caenorhabditis elegans...

High-risk human papillomaviruses (HPVs) promote malignant progression through sustained expression of the viral oncoprotein E6, which drives degradation of the tumor suppressor p53 and creates an oncogenic dependency in HPV-positive cancers. Here, we identify a genotype-defined therapeutic vulnerability by selectively and irreversibly inactivating HPV-16 E6 through covalent targeting a cysteine proximal to its E6AP-binding interface. Pharmacologic inhibition of E6 restored p53 protein stability...

The gut microbiome undergoes dynamic, sex-dependent changes across the lifespan. However, comprehensive studies examining the combined effects of age and sex are limited. This study investigated both compositional and functional alterations in the gut microbiome of young (4 months, n = 14) and aged (20 months, n = 20) C57BL/6 J mice of both sexes using 16S rRNA gene (V3-V5) sequencing. Microbial community structure and predicted functional profiles were analyzed via QIIME2 and PICRUSt2, with...

Magnesium is traditionally viewed as a permissive electrolyte required for cellular viability. Emerging evidence, however, reveals a more central role for Mg^(2+) as an active regulator of mitochondrial bioenergetics and metabolic resilience. In this Review, we synthesize recent advances in renal magnesium handling, mitochondrial Mg^(2+) transport, and MgATP chemistry to propose a unifying framework in which magnesium functions as a bioenergetic checkpoint. At the cellular level, Mg^(2+)...

Temporal prediction is the ability to anticipate the likely time of occurrence of events and is important for adaptive behaviour in our everyday lives. Studies indicated that predictive aspects of environmental stimuli can be leveraged to reduce reaction times and enhance stimulus processing. Particularly, a recent study showed that this optimized behaviour is associated with a phase adjustment of ongoing neural oscillations aligning with the expected onset of upcoming stimuli. In ageing, there...

Against the backdrop of an accelerating global aging population, the epidemiological correlation between cognitive impairment and osteoporosis has become increasingly prominent. These two conditions exhibit a profound pathological coupling mediated by the bidirectional regulatory network of the "bone-brain axis." The operation of this axis is rooted in an intricate neuro-skeletal signaling network involving hormonal dysregulation, systemic inflammatory cascades, and the aberrant regulation of...

Whether new neurons contribute to human cognition in old age remains debated. Recently in Cell Stem Cell, Tosoni et al.¹ show that immature-neuron transcriptional programs persist in the aged dentate gyrus and that their molecular state, not simply their abundance, tracks Alzheimer's pathology and cognitive resilience.

Lysine63 polyubiquitination is a prevalent post-translational modification in the central nervous system. Deficiency of CYLD, a lysine63-specific deubiquitinase, is linked to synaptic dysfunction and neurodegenerative disorders. However, our understanding of how CYLD contributes to the manifestation of neuronal deficits, particularly in the context of ageing, remains limited. Here, we report that CYLD-1 is essential for physiological lifespan in the nematode Caenorhabditis elegans. Neuronal...

The decline of glomerular filtration is a hallmark of aging. Methylglyoxal (MG) is a uremic toxin known to induce aging-like changes; however, whether its mechanism of action is similar remains unclear. We compare the underlying mechanisms of MG and aging using Drosophila nephrocytes as a model. In addition to lower body weight, reduced locomotion, and shorter lifespans, MG caused filtration defects and induced cellular senescence in nephrocytes similar to the effects of aging, with a...