Aging & Longevity

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...

Although the causal association between aging and osteoarthritis (OA) has been documented, our understanding of the underlying mechanism remains incomplete. To define the regulatory molecules governing chondrocyte aging, we performed transcriptomic analysis of young and old human chondrocytes from healthy donors. The data predicted that GATA-binding protein 4 (GATA4) may play a key role in mediating the difference between young and old chondrocytes. Results from immunostaining and western blot...

Aqueous zinc-ion batteries have advanced rapidly, but practical deployment is limited by excessive negative-to-positive (N/P) ratios (>50), decreasing the energy density. Zinc powder anodes can lower N/P, yet their high specific surface area accelerates parasitic reactions and shortens lifespan. Here we report a high-loading and highly reversible dry-processed zinc powder anode with a non-electrochemically driven solid-electrolyte interphase (SEI). The dry process retains a homogeneous...

Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease...

Resting-state electroencephalography (EEG) provides a sensitive measure of large-scale neural dynamics and has been widely used to characterize age-related changes in brain function. However, many prior studies have relied on relatively small samples or single-condition recordings, limiting the generalizability of findings. In this study, we investigated normative age-related trajectories of EEG spectral features across eyes-closed (EC) and eyes-open (EO) conditions in a large cohort of healthy...

CONCLUSION: This study delineates two IC profiles among Chinese older adults. The XGBoost-based model was explored for rapid IC profile classification. These findings highlight heterogeneity in IC and support the feasibility of a simplified digital approach, with external validation warranted.

CONCLUSION: This study shows that the presence of MASLD is significantly associated with an increased risk of a worse depression trajectory. In subgroup analysis, this relationship was particularly pronounced amongst females and among individuals with key cardiometabolic morbidities such as dyslipidaemia.

Epidemiological links between cognition and body physiology in aging are well established, but their strength and drivers remain unclear. Which physiological systems - from body composition to cardiovascular, pulmonary, renal, hepatic, immune, metabolic, and musculoskeletal - best predict cognition, and to what extent are cognition-body associations linked to brain variation across aging? We examined 19 physiological phenotypes alongside three neuroimaging modalities in over 30,000 UK Biobank...

Myeloid cells, including microglia and perivascular macrophages, are central to Alzheimer's disease (AD) neurobiology, yet their role remains incompletely understood. We profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 donors spanning the lifespan and showing varying degrees of AD neuropathology. We delineated six subclasses comprising 13 transcriptionally distinct subtypes and identified adaptive changes associated with aging and AD progression. Here we show that a...