Aging & Longevity

A Scalable Organoid Model of Urothelial Aging for Metabolic Interrogation, Infection Modeling, and Reversal of Age-Associated Changes

1 week 2 days ago
Aging leads to a progressive decline in overall bladder function resulting in lower urinary tract symptoms and increased susceptibility to infections. However, tissue-specific mechanisms of aging, specifically the contributions of the urothelium, remain elusive. Here, we introduce mouse bladder epithelium-derived organoids (mBEDOs) as a scalable platform to model urothelial aging. mBEDOs from aged mice recapitulate key features of age-associated cellular reprogramming, including oxidative...
Adwaita R Parab

A roadmap for conducting more inclusive research on brain resilience in ageing and dementia

1 week 2 days ago
The variability in cognitive and brain ageing trajectories may be influenced by inter-individual and community-level differences in resilience that result from differential exposures to social and structural determinants of health and be affected by an individual's sex and gender. However, no clear guidance exists on how to best integrate these diversity-related factors (that is, sex, gender and social and structural determinants of health) into clinical and cognitive neuroscience research on...
M Natasha Rajah

Social frailty, functional ability and social capital: a study among urban slum older adults in Tamil Nadu, India-convergent parallel mixed method study

1 week 2 days ago
BACKGROUND: Social frailty and reduced functional ability are major challenges among older adults in urban slums, yet the mechanisms linking these factors remain poorly understood. Social capital may buffer the effects of social frailty, but evidence is limited in urban slums context. The protocol study hypothesized that higher social capital is associated with lower social frailty and better functional ability among older adults.
Sai Prashanthini Sivakumar

Cortical O<sub>2</sub> supply and metabolism are suppressed in the aged mice

1 week 2 days ago
Current evidence suggests that the rejuvenating effects of parabiosis on brain function arise from the exchange of blood factors that enhance synaptic plasticity, promote neurogenesis, and reduce neuroinflammation in aged animals. However, aging is also associated with diminished tissue oxygenation. Here, we report that erythrocytes (red blood cells, RBCs) from aged mice exhibit reduced responsiveness to low oxygen tension (PO(2)) and release O(2) slower than those from young mice. In vivo,...
Hongyi Kang

MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis

1 week 2 days ago
Mitochondrial dysfunction is a hallmark of aging and a key contributor to age-related diseases including cardiovascular disease. However, molecular pathways that safeguard mitochondrial homeostasis in the aging heart remain poorly understood. Here, we identify MTFR1L as a regulator of mitophagy that binds p-S65-Ub, a key signal amplifying the PINK1/Parkin axis. We find that MTFR1L is enriched in metabolically active tissues, particularly in the heart, where it regulates Parkin signaling. Genetic...
Le Shi

Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders

1 week 2 days ago
Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in...
Spandana Rajendra Kopalli

Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging

1 week 2 days ago
The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC)...
Hai-Yan Hou

CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction

1 week 3 days ago
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer, but resistance inevitably develops. In triple-negative breast cancer (TNBC), the efficacy of CDK4/6i remains uncertain. Our study shows that the selective CDK2 inhibitor BLU-222, while effective alone, enhances synergistic activity when combined with CDK4/6i in resistant HR+/HER2- and TNBC models,...
Linjie Luo

Silencing lipid catabolism determines longevity in response to fasting

1 week 3 days ago
Oscillations between lipid anabolism and catabolism are essential for maintaining cellular health during metabolic fluctuations. Fasting, a conserved determinant of aging, improves disease outcomes and extends lifespan, yet the relative contributions of lipid catabolism versus its attenuation to fasting-induced longevity remain unresolved. The metabolic flexibility of C. elegans under variable nutrient availability provides a powerful system to address this question. We show that lifespan...
Lexus Tatge

Single-cell atlas of human lung aging identifies cell type dyssynchrony and increased transcriptional entropy

1 week 3 days ago
Age is a major risk factor for lung disease. We characterized the changing cellular, transcriptional, and genomic landscape of human lung aging using single-cell RNA sequencing. We find that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest transcriptional changes. Among alveolar epithelial cells, aging is associated with a decreased relative proportion of surfactant-expressing SPC^(high) AT2 cells. Among alveolar capillary cells, we...
Ruben De Man

DNA methylation-based surrogate markers of C-reactive protein and their associations with health-related traits

1 week 3 days ago
Several methylation-based surrogate markers of C-reactive protein (mCRP) have been proposed and used to assess the risk of age-related phenotypes and construct novel ageing markers. We aimed to (i) assess the variance in plasma CRP explained by several mCRP markers; (ii) compare their associations with three health-related traits: mortality, body mass index (BMI), and PCGrimAge; and (iii) assess the stability of CRP and mCRP over a decade. Blood samples were collected from 947 participants in...
Danmeng Lily Li

Targeting age-related LINE-1 activation alleviates cardiac aging

1 week 3 days ago
Cardiac aging is a major driver of cardiovascular diseases and associated mortality, yet its therapeutic options are limited. While long interspersed nuclear element-1 (LINE-1) retrotransposons are known to drive cellular senescence, their role in cardiac aging is poorly defined. Here we showed that LINE-1 expression increased in the heart with age. To investigate their role in cardiac aging, we generated cardiomyocyte-specific Mov10-knockout mice, which failed to suppress LINE-1. These mice...
Chaofan Yang

Molecular damage associated with ageing drives inflammation in cardiovascular disease

1 week 3 days ago
Chronic inflammation has long been recognized as a major risk factor for and a causal contributor to cardiovascular disease (CVD). However, advances in omics technologies and deepening insights into CVD pathogenesis have expanded our understanding of the underlying mechanisms. Inflammation is now seen not as an isolated cause, but as one of several biological responses to cumulative tissue damage over time. In this Review, we propose that inflammation initially functions as a resilience...
Allison B Herman

EFFECT OF A NEW PHYTOCOMPASSION ON THE CONTRACTILE ACTIVITY OF LYMPH NODES IN OLD ANIMALS

1 week 3 days ago
CONCLUSION: Phytocorrection proved to be effective in stabilizing the structural components of the lymph nodes, which maintained their contractile function at an adequate level. The composition is a geroprotector, and the biologically active substances in the phytocomposition correct and stimulate the lymph nodes' own transport function. Activation of the contractile activity of the lymph nodes is an important link in the body's anti-aging. This phytocorrection may have a wider application.
Georgiy Demchenko

Myelin is repaired by constitutive differentiation of oligodendrocyte progenitors

1 week 3 days ago
Oligodendrocytes form myelin sheaths around axons to enable rapid signaling within neural circuits. The generation of new oligodendrocytes through differentiation of oligodendrocyte precursor cells (OPCs) promotes myelin plasticity and repair in the adult brain. Here, we performed genetic interrogation and in vivo analysis of OPCs in the mouse brain to determine their differentiation dynamics. Our results show that OPCs attempt to differentiate throughout the adult central nervous system with...
Yevgeniya A Mironova

Lactucopicrin promotes the autophagic degradation of MAP2K4/MKK4 by mediating CCDC50 palmitoylation to alleviate osteoarthritis progression

1 week 3 days ago
Macroautophagy/autophagy plays a crucial role in maintaining cellular homeostasis and protecting against osteoarthritis (OA). Its dysregulation contributes to OA progression by promoting chondrocyte senescence, inflammation, and cartilage degradation. Enhancing autophagic activity thus represents a promising therapeutic strategy for OA. In this study, we identified lactucopicrin (LCP) as an effective autophagy activator that alleviates OA progression in a mouse model induced by the...
Wenjun Li

Follicle-stimulating hormone linked to cognitive decline and amyloid burden in postmenopausal women

1 week 3 days ago
INTRODUCTION: Women have a higher risk of developing Alzheimer's disease (AD) than men, with hormonal changes during menopause being a potential factor. However, the exact relationship between these hormonal changes, cognitive function, and AD pathology is not fully understood. This study investigates the differential associations between serum follicle-stimulating hormone (FSH) and estradiol levels with cognitive function and cerebral amyloid-βeta (Aβ) deposition, quantified using amyloid...
Sheng-Min Wang
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