Aging & Longevity
Building an Ontology of Resilience: Insights from the Physical Resilience Literature
Physical resilience is a term used to describe an individual's response to physical and physiological stressors across the fields of gerontology and rehabilitation sciences. However, the term has not yet undergone a rigorous examination of its underlying assumptions, which has hindered its theoretical development and empirical measurement. This paper reviews the existing definitions of physical resilience in the context of human physical and psychological systems to examine its underlying,...
Regulatory Mechanisms of Age-related Degenerative Diseases: Insights from the Gut Microbiota-Cellular Senescence Interaction Network
Global population aging has sharply increased the prevalence of age-related degenerative diseases, posing severe challenges to global public health and socioeconomic stability. Growing evidence links these disorders to the bidirectional crosstalk between gut microbiota and cellular senescence, yet the integrated interaction network governing multi-organ degeneration remains poorly defined. Age-related gut microbial remodeling reshapes metabolite profiles: beneficial metabolites mitigate cellular...
Author Correction: Titration of RAS alters senescent state and influences tumour initiation
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Advancing healthy ageing in Greece: the WHO ICOPE protocol within the JA PreventNCD framework
CONCLUSION: This protocol represents the first structured effort to embed the WHO ICOPE model within the Greek healthcare system. By integrating professional training, community-based assessment, and digital documentation, the initiative aims to strengthen person-centred care, prevent dependency, and align national ageing policies with international standards.
The glymphatic system and meningeal lymphatic vessels: from physiology to pathophysiology, with insights into visualization
The lymphatic system plays critical roles in immune defense, fluid homeostasis, substance metabolism, and cellular communication. Traditionally, it was believed that the vertebrate brain lacked a classical lymphatic system. Studies have revealed the presence of the glymphatic system (GS) and meningeal lymphatic vessels (MLVs), which are thought to play important roles in regulating material transport and immune processes within the central nervous system (CNS), in ways that resemble aspects of...
Activating p53<sup>Y220C</sup> with a mutant-specific small molecule
TP53 is the most commonly mutated gene in cancer, but it remains recalcitrant to clinically meaningful therapeutic reactivation. We present here the discovery and characterization of a small molecule chemical inducer of proximity that activates mutant p53. We named this compound TRanscriptional Activator of p53 (TRAP-1) due to its ability to engage p53^(Y220C) and BRD4 in a ternary complex, which potently activates mutant p53 and triggers robust p53 target gene transcription. Treatment of...
Distribution of dementia severity and its functional correlates in community-dwelling older adults in Vietnam
CONCLUSION: This study provides community-based evidence on dementia severity among older adults in two districts of Hai Duong province, Vietnam, showing that more than half of participants had moderate-to-severe dementia. Functional independence and quality of life were associated with dementia severity and may represent important considerations when designing community-based dementia care strategies.
SIRT1 Downregulation by Advanced Glycation End Products Activates RANKL-Dependent Osteoclast Signaling and Drives Chondrocyte Senescence During Osteoarthritis Development
Advanced glycation end products (AGEs) accumulate with aging and metabolic stress and are increasingly implicated in osteoarthritis (OA) pathology. However, how AGEs regulate osteoclast-chondrocyte signaling remains poorly defined. Here, we integrated proteomic and transcriptomic analyses with machine learning to identify molecular networks altered by AGEs in osteoclasts. SIRT1 emerged as a central regulator suppressed following AGE exposure. Loss of SIRT1 deacetylase activity activated the...
Stress-induced CXCL13 regulates pancreatic exocrine homeostasis, age-related chronic inflammation, and cancer progression
Pancreatic cancers, whose incidence increases with age, are often refractory to treatment. Here, we identified a core mechanism shared by physiological homeostasis, senescent cell accumulation during aging, and pancreatic cancers. Pancreatic acinar cells, when stressed, secrete CXCL13, which protects stressed cells while transiently activating paracrine Hippo/YAP signaling to induce proliferation and PD-L1-mediated immune protection to maintain organ homeostasis. In the aged pancreas,...
Low genetic risk for coronary artery disease underlies multigenerational longevity and healthy aging
Aging is a major risk factor for chronic diseases. Unlike the general population, members of long-lived families maintain exceptional health as they age, with over 10 years delayed onset of their first chronic disease. We therefore hypothesize that one of the key features explaining healthy survival up to high ages (longevity) is the absence of chronic disease risk alleles. We investigated this hypothesis in the Leiden Longevity Study, a cohort with data from more than 420 long-lived families in...
ZNRF2-mediated CD-M6PR degradation and lysosomal dysfunction aggravate cellular senescence and aging
Lysosomal dysfunction is a hallmark of cellular senescence, yet the mechanisms governing lysosomal protein trafficking remain incompletely understood. Here, we show that CD-M6PR, a principal receptor for lysosomal enzyme transport, is markedly reduced in senescent fibroblasts and in aged mice and humans, and that its loss correlates with the severity of autolysosomal impairment. Mechanistically, the reduction of CD-M6PR in senescent cells mainly stems from the accelerated proteasome-mediated...
Educating older adults to use technologies for health management in social settings: perspectives of older adults and community workers
CONCLUSION: The needs of older adults and community workers in utilizing technology for health exhibit a multi-layered interaction. Older adults require simplified technologies and social support, and community workers demand technical training and policy backing. The study's findings support a reframing of immediate recommendations towards age-friendly design, structured training for community workers, and policy support for resources. Developing artificial intelligence-assisted tools is a...
Construction of a classification model for dementia among Brazilian adults aged 50 and over
CONCLUSION: The findings reinforce the multidimensional nature of dementia and the importance of accessible factors for supporting screening/triage and prioritization in primary care. Strengthening public policies focused on promoting brain health can contribute significantly to the efficient allocation of resources in primary care and dementia prevention in Brazil.
Insights of traditional Indian anti-aging herbal beverages, network pharmacology, and perspectives
Plants have served as important sources of medicine since prehistoric times, forging a strong connection between humans and their environment. This relationship has yielded valuable insights into the therapeutic use of herbs for various health conditions. The current study aims to gather scientific evidence about traditional Indian anti-aging herbal beverages that have been practiced for centuries. We conducted a literature search through online databases, research articles, search engines, and...
Characterizing the metabolomes of microglia, astrocytes and neurons in ageing and Alzheimer's brains
Neurons and glia are distinct in their morphology, development and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here we purified microglia, astrocytes and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized...
Autophagy revealed as a targetable vulnerability in senescent cells by cell painting phenotypic profiling: a mechanistic study of MCOPPB and related compounds
Senescent cells accumulate with age and contribute to tissue dysfunction and chronic inflammation. Senolytic agents that selectively eliminate senescent cells hold therapeutic promise; however, few mechanistic classes have been established. Using Cell Painting-based morphological profiling, we identified a distinct cluster of senolytic compounds comprised of both known and novel autophagy inhibitors, including AZ191, bafilomycin A1, chloroquine, daurisoline, dauricine, MCOPPB, and its derivative...
Inflammatory protein epigenetic scores (EpiScores) and cognitive function in the longitudinal Swedish adoption/twin study of aging (SATSA)
Protein epigenetic scores (EpiScores) are DNA methylation (DNAm)-based proxies for circulating protein levels and may provide insights into inflammation-cognition relationships. Although some EpiScores have been linked to cognitive decline, it remains unclear whether these proxies show similar associations in other cohorts, and whether their effects vary across distinct cognitive domains. We aimed to evaluate the associations between inflammatory proteins EpiScores and cognitive functions...
Long-term cerebrovascular effects of cyclophosphamide and vincristine: endothelial senescence, impaired DNA repair signaling, and blood-brain barrier dysfunction
Chemotherapy-related cognitive impairment is increasingly recognized as a long-term consequence of cancer treatment, yet the contribution of the cerebrovascular system remains poorly defined. In this study, we investigated the long-term effects of clinically relevant treatment regimens with cyclophosphamide (CP) and vincristine (VIN) on cerebrovascular cellular senescence, associated molecular signatures, and downstream functional outcomes, including disruption of blood-brain barrier (BBB)...
A Decline in Follicle Cell Function Is a Major Driver of Drosophila Ovarian Aging
The ovary is one of the first organs to lose functionality with age. We found that aging of the Drosophila ovary is characterized by an accumulation of phenotypes in the somatic compartment, including failure of the follicle cells to encapsulate germ-cell cysts, an extended S phase, and increased DNA damage. In aged ovaries, follicle encapsulation defects are associated with the lack of a germ-cell cyst checkpoint in early oogenesis. Single-cell RNA sequencing revealed that, across all cell...
RETRACTION: Antileukotriene Therapy by Reducing Tau Phosphorylation Improves Synaptic Integrity and Cognition of P301S Transgenic Mice
P. F. Giannopoulos, J. Chiu, and D. Praticò, "Antileukotriene Therapy by Reducing Tau Phosphorylation Improves Synaptic Integrity and Cognition of P301S Transgenic Mice," Aging Cell 17, no. 3 (2018): e12759, https://doi.org/10.1111/acel.12759. The above article, published online on 01 April 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Monty Montano; The Anatomical Society; and John Wiley & Sons Ltd. The retraction has...
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