Aging & Longevity

CONCLUSION: Temporal gait components were associated with age primarily through cognition-related pathways and may serve as candidate digital markers of cognitive impairment, although longitudinal validation is required. Interpretation is limited by the cross-sectional design and the restricted representation of individuals with moderate-to-severe dementia.

Intervertebral disc degeneration (IVDD) is a leading global cause of chronic pain and functional impairment. The senescence of endplate chondrocytes (EPCs) associated with the IVDD cascade, with mitochondrial homeostatic imbalance serving as the central pathological key mediator. EPCs inhabit a physiological niche defined by hypoxia, limited nutrients, and high mechanical loads, requiring precise metabolic regulation and mitochondrial quality control. This review integrates recent advances in...

Immunosenescence refers to the progressive decline in immune system functionality associated with aging, with thymic involution identified as a primary driver of this process. The thymus, the central organ for T cell development, begins to atrophy from puberty onward, resulting in a marked reduction in naive T cell output and a significant decrease in the diversity of T cell receptor (TCR) repertoires. This decline compromises the immune system's capacity to mount effective responses against...

Long-lived proteins provide a uniquely informative substrate for studying the molecular chemistry of human ageing, and the eye offers one of the most accessible and spatially resolved systems for examining this process. The lens remains the principal model: its central crystallins are synthesized during embryonic and early postnatal life and are retained throughout the lifespan, thereby preserving a cumulative record of irreversible chemical damage. We then extend this framework to other ocular...

CONCLUSIONS: Socioeconomic inequalities in functional ageing are apparent in England and Canada, are larger in England than in Canada, and are not fully explained by common risk factors. These findings suggest that multilevel approaches, combining individual-level interventions with structural measures, are required to address socioeconomic inequalities and cross-country differences in functional ageing. Variation in wealth associations by sex suggests that approaches to reducing socioeconomic...

CONCLUSION: Age and VF are nonlinearly associated across adulthood, with educational attainment being a major determinant. Higher central adiposity is associated with lower VF and moderates the associated with age. Lower-limb functional performance was independently associated with VF, potentially reflecting a functional pathway linking adiposity, mobility, and cognitive aging.

Female reproductive aging is associated with ovarian functional decline, leading to infertility. During aging, biochemical and biophysical changes in the ovarian extracellular matrix (ECM) occur, yet how these properties affect follicle growth and oocyte quality remains poorly understood. Here we describe spatiotemporal changes in the ovarian ECM with age using mass spectrometry, immunohistochemistry, and nanoindentation. While follicle stiffness remains unchanged, stromal matrix remodeling is...

As global population aging accelerates, maintaining locomotor function in later life has become a critical biomedical challenge. This study investigates the effects of three bioactive compounds-Luteolin (Lut), Glycitein (Gly), and α-Spinasterol (α-Spin)-isolated from the traditional Chinese medicinal herb Codonopsis pilosula (Dangshen), on age-related locomotor decline using the Caenorhabditis elegans (C.elegans) model. We demonstrate that Lut and Gly significantly ameliorate the deterioration...

Age-related cognitive decline is a major social and medical challenge, but its mechanisms remain poorly understood; prevention and therapy are unsatisfactory. The tachykinin hemokinin-1 (HK-1), encoded by the Tac4 gene, is expressed in brain regions involved in learning and memory and has been implicated in neuroimmune regulation, but its contribution to age-dependent cognitive impairment remains unclear. Here, we investigated whether endogenous HK-1 modulates cognitive performance during aging....

Growth hormone (GH) exerts complex effects on metabolism, cognition, and overall physiological well-being, and its secretion is highly regulated by the circadian clock. The Growth Hormone Receptor Knockout (GHR-KO) mouse, a model of GH insensitivity, characterized by chronically elevated circulating GH, provides a unique opportunity to examine the consequences of disrupted GH signaling during aging. Given the close relationship between circadian rhythmicity and GH secretion, we investigated sex-...

CONCLUSIONS: Research investigators, staff, Veterans, and caregivers identified several cross-cutting challenges that are important in the recruitment and retention of older rural Veterans in research. The adaptations proposed here demonstrate that the 5Ts Framework can extend to intersectional aging populations, providing a model for broader representation in research.

Microglia, the brain's resident immune cells, are transcriptionally diverse and highly dynamic, but during aging and disease they lose their transcriptomic flexibility and adopt a chronically activated state that is associated with neuroinflammation and pathology. An emerging transcriptomic process that is also increasingly implicated in brain aging, neuroinflammation, and disease is the dysregulation of transposable elements (TEs), repetitive genomic sequences with the potential to cause...

Female fertility depends on a finite pool of oocytes that depletes during aging^(1,2), yet the spatiotemporal dynamics of this depletion remain poorly understood. Traditional methods obscure the three-dimensional architecture of the ovary, limiting quantitative insights. Here we combine light-sheet microscopy, artificial intelligence-driven segmentation and mathematical modeling to map over 85,000 oocytes in whole ovaries across the reproductive lifespan in mouse. We find that newly activated...

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There is little understanding of how aging serves as the strongest risk factor for several neurodegenerative diseases. Microglia undergo age-related maladaptive changes, including increased inflammation, impaired debris clearance, and cellular senescence, yet specific mediators that regulate these processes remain unclear. The aged brain is rejuvenated by youth-associated plasma factors, including tissue inhibitor of metalloproteinases 2 (TIMP2), which we have shown acts on the extracellular...

CRISPR has emerged as a next-generation gene-editing tool with the potential to target the molecular pathways associated with ageing and related disorders. It functions through RNA-guided Cas nucleases, directing DNA cleavage and utilizing the native DNA repair machinery for genetic manipulations. Advances in CRISPR technology have significantly enhanced the precision and flexibility of techniques for genome editing. The enzyme Cas9's ability to cut DNA at exact site has revolutionized genome...

Regular physical activity is beneficial for brain health. However, no research has explored whether physical activity level (PAL) assessed by the doubly labeled water method (PAL-DLW) is associated with brain volume and cognitive function. We investigated whether PAL-DLW, accelerometer-assessed PAL (PAL-Acc), and components of physical activity are associated with brain volume and cognitive function in older adults. We analyzed data from 49 participants with cardiometabolic or functional risks...

CONCLUSION: Age-associated inflammation is accompanied by activation of the IL6ST/JAK1-STAT1 signaling pathway, increased megakaryocyte apoptosis, and enhanced thrombopoiesis in aged mice. These findings suggest that inflammation-driven megakaryocyte remodeling may represent a compensatory mechanism for sustaining platelet production during aging and may contribute to the heightened thrombotic risk observed in older individuals.

CONCLUSION: PRMT6 exacerbates D-gal-induced cochlear aging by promoting asymmetric arginine dimethylation of FOXG1, accelerating FOXG1 degradation, and inhibiting mitophagy. The PRMT6-FOXG1-mitophagy axis represents a potential therapeutic target for D-gal-induced cochlear aging.

Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is...