Aging & Longevity

p62/SQSTM1 generates liquid-liquid phase-separated condensates that participate in diverse processes, including protein quality control (PQC) and autophagy. Nuclear p62 condensates were shown to act as ubiquitin- and proteasome-mediated degradation hubs, whereas the involvement of cytoplasmic condensates in this pathway has remained unclear. Here, we show that cytoplasmic p62 condensates serve as a hub for proteasomal degradation that displays distinct substrate preferences compared with nuclear...

Chronic kidney disease (CKD) is projected to become the fifth leading cause of mortality by 2040. Tubular senescence drives kidney fibrosis, but current treatments do not target senescent cells. Here, we identify nicotinamide-N-methyltransferase (NNMT) as a critical mediator of tubular senescence and kidney fibrosis. Human CKD microarrays link NNMT to senescence and fibrosis transcriptomic signatures, and diabetic kidney disease (DKD) biopsies show NNMT protein associating with p21, fibrosis,...

CONCLUSIONS: Higher acceptance was found for smart wearable devices for elder care purposes compared to the sensors and cameras at home. Presence of actual need such as risk of falling, practical care situations, as well as an overall emphasis on ensuring the safety of older persons, were observed to positively impact the acceptance of technologies. Our findings also impart significance of the role of caregiving stress as a driver to incorporating technical tools in elder care. Further research...

Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their...

Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these...

Biomolecular condensates are essential for cellular organization, yet their formation dynamics and molecular content exchange properties remain poorly understood. Here we show that flow cytometry provides a high-throughput, solution-based platform for analyzing condensate behavior at the single-droplet level. Using self-interacting NPM1 condensates as a model, we demonstrate that this approach quantifies phase behavior across protein and salt conditions, measures the partitioning of diverse...

Battery monitoring requires high accuracy and robustness throughout the entire lifespan to ensure safe and optimal operations. Here we introduce mechanistic leading residual learners to enhance the monitoring of battery charge and health states, as well as guide safety warnings, targeting large-scale applications. Leveraging prior knowledge from real-time filtering as primary guidance, complemented by mechanistic and statistical features, our approach significantly improves accuracy and...

Children with congenital heart defects increasingly survive to adulthood, but the non-physiological Fontan circulation imposed by current surgical palliation leads to significant sequelae and reduced lifespan. Restoring subpulmonic pumping function remains a long-standing goal, and there have been several attempts using regenerative medicine approaches. These efforts have lacked biomechanical rigor, however, and have not achieved the requisite functionality. Here, we introduce an analytically...

Defect microstructures, particularly dislocations, are pivotal in determining the functional properties of ferroelectric thin films. While their density is routinely considered, the critical role of their spatial configuration has remained largely unexplored and difficult to control. Here, we develop a controlled self-assembly strategy for dislocations in Bi(Fe,Mn)O(3) thin films on Ni-Cr that directly addresses this challenge. By employing a LaNiO(3) buffer layer, we template a...

Hematopoietic stem cells (HSCs) are multipotent self-renewing cells that give rise to all types of blood cells. Past research has identified that long-term hematopoietic stem cells in young mice and humans produce a balanced output of lymphoid and myeloid cells, while in old age, they are largely replaced by myeloid-biased HSCs (My-HSC). It has not yet been determined whether this transition results from epigenetic changes in a single population of HSC or if two or more subsets of HSCs exist...

Low concentrations of chemicals are widespread in the environment, but exploration of the effects of their chronic exposures on animal life span in the wild is limited. Field investigations showed that fish populations of lake skygazer (Culter dabryi) with chronic low-dose chlorpyrifos loads had shortened telomeres and truncated age structures. Laboratory experiments confirmed that chronic low-dose chlorpyrifos exposure induced telomere degradation and reduced survival in a dose- and...

Harms of chlorpyrifos emerge in polluted lakes and laboratory aquarium tanks.

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BACKGROUND AND OBJECTIVES: Increasing urbanization and the aging global population highlight cities as vital environments for promoting healthy aging. However, the relationship between characteristics of urban green spaces and older adults' mental well-being remains unclear.

Cellular morphological changes occur during cell life and diseases, such as senescence and cancer. Although the cellular conditions should be varied with the morphology changes, there have been no attempts to understand the cellular morphological changes by focusing on the intracellular molecular environment and elucidating the behaviour of nucleic acids. Nucleic acids can form hierarchical secondary and higher-order structures due to intermolecular interactions and other factors. Additionally,...

Ribosomal DNA (rDNA) encodes the 18S, 5.8S, and 28S rRNA, accounting for ∼70% of cellular transcription. Despite its essential role and links to cancer and aging, quantifying rDNA instability in mammals remains challenging due to its repetitive organization and inherent heterogeneity. Here, we developed a murine rDNA FISH probe and genomic tools tailored for laboratory mouse strains. The results confirmed rDNA cluster locations, revealed substantial inter- and intra-strain as well as...

Cancer cells precisely modulate replication stress to sustain genomic instability without triggering lethal DNA damage, yet regulators enabling this delicate balance remain largely unknown. Here, we identify N-methyl-D-aspartate receptor synaptonuclear signaling and neuronal migration factor (NSMF) as a novel and critical regulator of replication stress in colorectal cancer (CRC). NSMF expression is significantly elevated in CRC tissues and correlates closely with elevated replication stress. In...

Aging is accompanied by profound changes in energy metabolism, yet the underlying drivers and modulators of these shifts remain incompletely understood. Here, we investigated how life-history evolution shapes metabolic aging and pharmacological responsiveness by leveraging Drosophila melanogaster lines divergently selected for reproductive timing. We measured organismal oxygen consumption rate and performed untargeted metabolomics in young and old flies of both sexes from long-lived "O" lines...

Immune cells from the skull marrow reach the meninges through bone channels. In this issue of Immunity, Eme-Scolan and colleagues show that these channels form neonatally and can be remodeled to alter immune access to the brain's borders. Their work suggests that the skull is a developmental checkpoint for neuroimmune defense, potentially shaping vulnerability or resilience across the lifespan.

Dual-task walking, performing a secondary task while walking, challenges attentional and motor resources and has been linked to increased fall risk. While cognitive dual tasks are most often studied, physical (e.g., load carriage) and "combination" tasks such as obstacle crossing may also impact gait. Whole-body angular momentum and its variability provide sensitive markers of locomotor stability. We investigated how dual-task type influences gait mechanics and stability in younger and older...