Aging & Longevity

Copper and iron are redox-active micronutrients with tightly coupled homeostasis, yet how copper modulates iron-dependent stress responses remains unclear. Using Saccharomyces cerevisiae under nutrient-limited conditions, we uncoupled proliferative growth from long-term survival to dissect metal-dependent adaptation. Copper selectively preserved survival without affecting growth, whereas iron showed similar effects. Iron chelation impaired growth and suppressed electron transport chain gene...

Bioelectrical phase angle is an integrated marker of cellular integrity, fluid distribution, nutritional status, and physiological reserve, but its relationship with objective sensory function in later life remains unclear. This population-based cross-sectional study analyzed adults aged 40 years or older from the 2022-2023 Korea National Health and Nutrition Examination Survey. Whole-body phase angle at 50 kHz was assessed using bioelectrical impedance analysis, and pure-tone audiometry was...

While immunosenescence is increasingly implicated in chronic inflammatory disorders, its precise pathogenic contribution to ulcerative colitis (UC) remains elusive. Here, we identify senescent CD8^(+) T cells as a distinct pathogenic population that exacerbates colitis, demonstrating that systemic senolytic treatment significantly attenuates disease severity. Mechanistically, nicotinamide adenine dinucleotide (NAD^(+)) metabolic dysregulation triggers mitochondrial dysfunction and cytosolic...

Reliable differentiation of Parkinson's disease/Lewy body dementia (PD/LBD) from frontotemporal dementia (FTD) affects treatment strategy and clinical trial eligibility, yet confirmatory biomarker testing remains costly and unevenly available. Whether routine cognitive trajectories can support testing prioritization has not been systematically quantified. We performed a progressive inclusion analysis of 1,129 National Alzheimer's Coordinating Center participants with PD/LBD (n = 385) or FTD (n =...

CONCLUSION: Collectively, our data suggest that high WM performance in midlife depends on the flexible modulation of autonomic and cortical resources, potentially facilitating the attentional mobilization necessary for cognitive coping. These neurophysiological signatures allow clearer distinction between a chronological aging profile and a successful cognitive aging profile.

Sarcopenia, the age-related loss of muscle strength and mass, contributes to adverse health outcomes in older adults. Exercise engages calcium (Ca^(2+))- and redox-dependent signaling pathways that enhance muscle performance and adaptation, whereas aging disrupts Ca^(2+) and redox homeostasis. CaMKII is a key transducer of both signals, raising the possibility that sustained CaMKII signaling becomes maladaptive with aging. Here, we show that CaMKII protein abundance is increased in aged mouse...

With the acceleration of global aging, the relationship between Alzheimer's disease (AD) and the glymphatic system (GS) has become a research hotspot in the field of neuroscience in recent years. Traditionally, the central nervous system was thought to lack a lymphatic system; however, research over the past decade has overturned this view. Studies have revealed the existence of GS and meningeal lymphatic vessels (mLVs) in the brain, which clear metabolic waste (such as amyloid-β and tau...

Mitochondria integrate bioenergetics, redox signalling, calcium handling, biosynthesis, apoptosis, and stress responses. Their contribution to ageing depends less on any single pathway than on the ability to sustain these functions through continuous maintenance, remodelling, and inter-organelle communication. This review proposes mitochondrial homeodynamics as a systems-level framework for that ability, which rests not on static preservation but on three linked capacities. Maintenance...

The limited benefits of high-density lipoprotein (HDL)-targeted therapies have shifted the research focus to HDL quality; some HDL subtypes may be pro-atherogenic and may counteract the potential benefits of HDL therapies. This study investigated the pathological mechanism of H5, a highly electronegative and compositionally abnormal HDL subfraction characterized by impaired cholesterol efflux. We used anion-exchange chromatography to separate HDL into five subfractions (H1-H5) from blood from...

As populations age worldwide, pathological neurodegeneration with subsequent cognitive decline has emerged as a pressing public health challenge. As effective treatments remain limited once neurodegeneration has occurred, prevention and delay of decline onset are crucial. While physical exercise is associated with improved cognition, exercise-specific mechanisms remain unclear. We therefore examined the effects of 12 weeks explosive lower-body resistance training (RT) in community-dwelling older...

Cerebral small vessel disease is a major contributor to stroke and cognitive decline and is characterized by white matter hyperintensities (WMH) and microstructural alterations detectable via diffusion-weighted imaging parameters, including free water (FW) and fractional anisotropy (FA). Hispanic/Latino populations experience a high burden of vascular risk factors. However, the impact of these factors on white matter integrity across diverse heritage groups remains underexplored in this...

No abstract

CONCLUSIONS AND IMPLICATIONS: Rural nursing homes exhibited disaster resilience under baseline disaster conditions but not during evacuation. It is possible that evacuation exposes rural nursing home residents to structural and operational constraints that may differentially compromise postdisaster survival. Future federal and state guidance may benefit from aligning preparedness standards with the distinct constraints of rural nursing homes.

Cellular senescence is one of the best-studied biological programs, yet it continues to reveal unexpected aspects. In this issue of Developmental Cell, Durik et al.¹ describe how senescent cells shed large cytoplasmic fragments that promote their survival and may represent a mechanism of communication with neighboring cells.

Somatic mutations accumulate throughout life in every cell, and this process constitutes one of the hallmarks of aging-genomic instability. Caloric restriction (CR) has been shown to extend lifespan across diverse species. Using high-fidelity duplex DNA sequencing of bulk liver, bulk kidney, hepatocytes, and cerebellar neurons, we found that CR in mice reduces genome-wide somatic mutation burdens across multiple tissues and cell types. CR reduced both substitution and insertion/deletion burdens,...

Current brain atlases are largely descriptive, cataloging correlative molecular snapshots such as gene expression signatures yet offering limited functional insight. Here, we develop a scalable, cell-type-resolved in vivo CRISPR interference (CRISPRi) platform enabling systematic gene function profiling in the mouse brain. Through genome-wide screens across four neuronal populations at three time points spanning youth to aging, we identify neuronal essential genes missed in vitro and define a...

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disorder characterized by marked clinical heterogeneity and incompletely understood genotype-phenotype correlations. While X-chromosome inactivation has been extensively investigated, the contribution of autosomal epigenetic mechanisms to phenotypic variability remains poorly defined. Here, we performed an exploratory genome-wide DNA methylation analysis in 32 AFD patients (22 females and 10 males; mean age 51.7 years) recruited...

GAIP-interacting protein C-terminal 1 (GIPC1/GIPC) is a well-established protein in the field of cancer biology. Recent studies have revealed that GIPC1 may exert opposing, context-dependent functions in various diseases or physiological processes, although the underlying regulatory mechanisms remain to be explored. Since GIPC1 contains a PDZ domain that interacts with various proteins, this domain is a promising therapeutic target. Molecular probes designed against the GIPC1-PDZ domain could...

As the body ages, chronic low-grade inflammation, metabolic dysregulation, and loss of tissue resilience occur; however, the pathways linking these processes have not been fully characterized. Beyond traditional host defence, the canonical complement C3a-C3AR1 signalling axis has been identified as an ageing-sensitive pathway. Studies involving naturally aged animals, older human cohorts, and models of age-related diseases indicate that chronic C3a-C3AR1 signalling can drive the reprogramming of...

The evolutionary biology of aging is fundamental to understanding the mechanisms of aging and how to develop anti-aging treatments. Thus far most evolutionary theory concerns the genetics of aging with limited physiological integration. Here we present an intuitive evolutionary framework built on how physiology is regulated and how this regulation itself ages. Life has evolved to secure reproduction and avoid system failure in early life, and it is the regulation that evolves in response to...